Band 16, Heft 1

Orexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep–wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present, studies that have been performed both domestically and abroad have confirmed that orexin and its receptors are closely associated with pain regulation. In this article, the research progress on acute pain regulation involving orexin is reviewed.

Adriamycin (ADR) is an important chemotherapy agent in many advanced cancers, but the emergence of drug resistance during treatment is a major limitation to its successful use. Recent studies have suggested that drug-resistant cells become less fit and their growth could be inhibited by parental cells without cytotoxic treatment. In this study, we examined the fitness differences between HeLa and HeLa/ADR cells. Compared with the parental cell line, HeLa/ADR cells showed significantly lower growth rates, both in vitro and in vivo . There was no difference in the apoptosis rate between them, but G1 arrest and reduced DNA synthesis were found in HeLa/ADR cells. Further study indicated that HeLa/ADR cells failed to compete for space and nutrition against parental cells in vivo . Taken together, we demonstrate that HeLa/ADR cells are less fit and their growth can be inhibited by parental cells in the absence of ADR; therefore, the maintenance of a certain amount of ADR-sensitive cells during treatment may facilitate the control of the development of ADR resistance.

Spermidine is important for the hypothalamic control of pituitary secretion of hormones involved in neuroendocrine functions in mammals. In this study, the effect of exogenous spermidine on the expression of genes and proteins related to polyamine metabolism and polyamine levels was examined. The results indicated that treatment with spermidine at 0.05 mg/g (BW) significantly increased the levels of Oaz 1 mRNA and protein expression and decreased putrescine content in mouse hypothalamus ( p < 0.05). The administration with spermidine at 0.10 mg/g significantly increased the levels of Oaz 1, Oaz 2, and Odc expression in mouse hypothalamus ( p < 0.05). Treatment with spermidine at 0.05 mg/g significantly increased the levels of Ssat mRNA expression and reduced the level of Smo mRNA expression in mouse hypothalamus ( p < 0.05). Putrescine concentrations in the hypothalamus after the administration of spermidine at 0.10 and 0.15 mg/g were significantly higher than those in the control group ( p < 0.05). The concentration of both spermidine and spermine in the hypothalamus after the administration of spermidine at 0.15 mg/g was decreased significantly ( p < 0.05). In summary, our results indicate that exogenous spermidine affects polyamine homeostasis in the mouse hypothalamus by modulating the expression of genes and proteins related to polyamine metabolism.

Background Lymphoma with intraocular metastasis is an uncommon and serious disease. We describe a case of diffuse large B-cell lymphoma (DLBCL) with iris metastasis. Meanwhile, we refer to published case reports retrieved via a PubMed search to summarize this rare disease. Case presentation Glaucoma and uveitis symptoms were found in the left eye of a 50-year-old woman upon admission to the hospital. After treatment and pathological examination, the iris of her left eye was diagnosed with DLBCL. Given the patient’s unfavorable treatment options in the local hospital, primary enucleation was offered as a therapeutic option. Conclusions Iris metastasis of systemic lymphoma is an extremely rare ophthalmic disease with poor prognosis. Ophthalmologists should be able to definitively and differentially diagnose eye symptoms and pay attention to systemic conditions to provide a series of optimized treatments.

Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo . PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo . PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

Background The objective of this study was to investigate the relationship among hypersensitive C-reactive protein to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and the CURB-65 score for community-acquired pneumonia (CAP) severity. Methods Clinical data and laboratory indicators of 82 patients with CAP and 40 healthy subjects were retrospectively analysed. The relationship among CAR, FAR, and the severity of CAP was then analysed. Results CAR and FAR in patients with low-risk CAP were significantly higher than those in the normal control group ( P < 0.05). CAR and FAR in patients with medium–high-risk CAP were further increased compared with those in patients with low-risk CAP ( P < 0.05). CAR and FAR were positively correlated with hypersensitive C-reactive protein, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and CURB-65 scores ( P < 0.05). In the receiver operating characteristic curve for predicting severe CAP, the area under the curve of combining four biomarkers (CAR + FAR + NLR + PLR) was the largest. CAR was also an independent risk factor for severe CAP (OR = 8.789, 95% CI: 1.543–50.064, P = 0.014). Conclusions CAR and FAR may be used as the inflammatory markers for CAP severity evaluation.

Several articles have indicated that circular RNAs are involved in pathogenesis of human cancers. Nevertheless, the role of circ_0091579 in hepatocellular carcinoma (HCC) progression remains to be revealed. Quantitative reverse transcriptase polymerase chain reaction was carried out to examine the expression of circ_0091579 and miR-1287. The proliferation of HCC cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was performed to analyze cell cycle progression and apoptosis. Western blot assay was conducted to detect the protein expression of CyclinD1, Cleaved caspase3, and pyruvate dehydrogenase kinase 2 (PDK2). Cell glycolysis was evaluated by measuring the uptake of glucose, the production of lactate, and extracellular acidification rate. The target relationship between miR-1287 and circ_0091579 or PDK2 was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA-pull down assay. The enrichment of circ_0091579 was enhanced in HCC tissues ( n = 77) and four HCC cell lines (HB611, Huh-7, MHCC97, and SNU423) compared with adjacent non-tumor tissues ( n = 77) and normal human liver cell line THLE-2. Circ_0091579 mediated the promotion of proliferation and glycolysis and the suppression of apoptosis of HCC cells. MiR-1287 was a direct target of circ_0091579 in HCC cells. MiR-1287 knockdown reversed the effects caused by circ_0091579 interference on the functions of HCC cells. PDK2 could bind to miR-1287 in HCC cells. Circ_0091579 upregulated the enrichment of PDK2 by acting as a sponge of miR-1287 in HCC cells. The influence caused by circ_0091579 intervention on HCC cells was attenuated by overexpression of PDK2. Circ_0091579 interference impeded the progression of HCC in vivo . Circ_0091579 deteriorated HCC by promoting the proliferation and glycolytic metabolism and suppressing the apoptosis of HCC cells via miR-1287/PDK2 axis.

Background Emerging evidence shows that long noncoding RNA (lncRNA) has been a novel insight in various diseases, including pneumonia. Even though lncRNA X-inactive-specific transcript (XIST) is well studied, its role in pneumonia remains to be largely unrevealed. Methods Expression of XIST, miRNA-30b-5p (miR-30b-5p), and CC chemokine ligand 16 (CCL16) was detected using reverse transcriptase quantitative polymerase chain reaction and western blotting; their interaction was confirmed by dual-luciferase reporter assay. Apoptosis, inflammation, and toll-like receptor 4 (TLR4)/NF-κB signaling pathway were measured using methyl thiazolyl tetrazolium assay, flow cytometry, western blotting, and enzyme-linked immunosorbent assay. Results Lipopolysaccharide (LPS) stimulation decreased cell viability and B cell lymphoma (Bcl)-2 expression, and increased cell apoptosis rate and expression of Bcl-2-associated X protein (Bax), cleaved-caspase-3, interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNF-α) in WI-38 cells. Expression of XIST and CCL16 was upregulated in the serum of patients with pneumonia and LPS-induced WI-38 cells, respectively; silencing XIST and CCL16 could suppress LPS-induced apoptosis and inflammation in WI-38 cells, and this protection was abolished by miR-30b-5p downregulation. Moreover, XIST and CCL16 could physically bind to miR-30b-5p, and XIST regulated CCL16 expression via sponging miR-30b-5p. TLR4 and phosphorylated P65 (p-P65) and p-IκB-α were highly induced by LPS treatment, and this upregulation was diminished by blocking XIST, accompanied with CCL16 downregulation and miR-30b-5p upregulation. Conclusions Silencing XIST could alleviate LPS-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and inhibiting TLR4/NF-κB signaling pathway.

Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant ( P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease ( P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.

Clopidogrel is an antiplatelet drug that displays significant interindividual variability in treatment response. Its bioavailability depends on the function of P-glycoprotein (P-gp), which is coded by a highly polymorphic ABCB1 gene. Thus, the aim of this study was to investigate the effect of ABCB1 genetic polymorphism on clopidogrel efficacy and safety and to determine the frequency distribution of its most common single nucleotide polymorphisms (SNPs) in 106 Montenegrin cardiology patients. Clopidogrel efficacy and safety were followed up during 1 year after hospitalization, with the lack of efficacy and adverse drug reactions observed in 11 (10.4%) and 8 patients (7.5%), respectively. Genotyping for ABCB1 SNPs rs1128503 (1236C > T), rs2032582 (2677G > A/T), and rs1045642 (3435C > T) was performed by the real-time PCR method, and the variant alleles were detected with the frequencies of 42.9, 44.8, and 52.8%, respectively. No significant association was observed between any of the examined genotypes and clopidogrel efficacy ( p = 0.253) or safety ( p = 0.424). Due to small sample size, co-treatment with other drugs, and other genetic factors not taken into account, we believe the absence of correlation between ABCB1 genotypes and indicators of clopidogrel efficacy and safety in this study should be apprehended conditionally, and that larger and better-controlled studies are warranted.

Tripterygium wilfordii multiglucoside (TWM) is a fat-soluble extract from a Chinese herb T. wilfordii , that’s used in treating rheumatoid arthritis, nephrotic syndrome and other skin diseases. Triptolide (TP) is a major active component in TWM. However, clinical applications of TWM are limited by its various toxicities especially hepatotoxicity. In recent studies, it has been reported that drug-induced liver injury (DILI) could induce the disorder of lipid metabolism in animals. Hence, this study focuses on the metabolic profile of fatty acids in TWM- and TP-induced liver-injured rats. In serum and liver tissue, 16 free and 16 esterified fatty acids were measured by gas chromatography coupled with mass spectrometry. Metabolic profile of serum fatty acids in rats with liver injury was identified by multivariate statistical analysis. The fatty acid levels in the serum of TWM- and TP-treated rats significantly decreased, whereas those in the liver tissue of TWM- and TP-treated rats obviously increased when compared with the vehicle-treated rats. Four free fatty acids were identified as candidate biomarkers of TWM- and TP-induced liver injury. Therefore, the targeted metabolomic method may be used as a complementary approach for DILI diagnosis in clinic.

This study aimed to explore the regulatory mechanisms of miR-338-3p and matrix metalloproteinase-2 (MMP-2) in neuroblastoma. Putative target interaction regions of miR-338-3p on MMP-2 were predicted by miRcode and miRbase bioinformatics tools. Relative expression of miRNA-338-3p and MMP-2 in neuroblastoma tissues and GI-LI-N and SK-N-SH cells was determined by reverse transcription polymerase chain reaction experiment. Furthermore, the cell proliferation was determined by Cell Counting Kit-8 assay, the cell apoptosis rate was analyzed by flow cytometry assay, and the cell invasion was evaluated by transwell assay. miR-338-3p expression was downregulated, whereas MMP-2 expression was upregulated in metastasis tissue site compared to that in primary tissue site in total. Furthermore, miR-338-3p overexpression suppressed proliferation, invasion, and epithelial–mesenchymal transition (EMT) of neuroblastoma cells but promoted apoptosis, and the knockdown of MMP-2 triggered similar effects. Furthermore, MMP-2 was directly targeted by miR-338-3p, and overexpression of MMP-2 rescued the inhibitory effects of miR-338-3p on human neuroblastoma cell progression. Collectively, these data demonstrated that miR-338-3p could suppress cell growth, invasion, and EMT pathway and induce apoptosis in neuroblastoma cells by targeting MMP-2. MiR-338-3p sponged MMP-2 to regulate the PI3K/AKT pathway in human neuroblastoma cells.

Treatment of neuropathic pain is far from satisfactory. This study sought evidence of a neuroprotective effect of alpha-lipoic acid (ALA) to treat neuropathic pain in a chronic constriction injury (CCI) rat model. A total of 48 rats were randomly divided into sham, CCI, or CCI + ALA groups. Mechanical and thermal nociceptive thresholds were evaluated as behavioral assessments. Dorsal root ganglia cells were assessed morphologically with hematoxylin and eosin staining and for apoptosis with P53 immunohistochemical staining. Compared with the sham group, the CCI group had a shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphologic manifestations, and increased numbers of satellite glial cells and P53+ cells. These changes were significantly reversed by treatment with ALA. Our study indicates neuroprotective effects of ALA on chronic neuropathic pain in a CCI rat model. ALA is potentially considered to be developed as a treatment for neuropathic pain caused by peripheral nerve injury, which requires further verification.

Background Emerging evidence has shown that circular RNAs (circRNAs) are vital regulators in osteosarcoma (OS) progression. However, the effects of circ_WWC3 in OS have not been explored. In this research, the functions and mechanisms of circ_WWC3 in OS were investigated. Methods Quantitative reverse trancription polymerase chain reaction (qRT-PCR) was adopted to determine the levels of circ_WWC3, WW and WWC3 mRNA, miR-421, and phosphodiesterase 7B (PDE7B) mRNA. RNase R assay was used to determine the characteristic of circ_WWC3. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide (MTT) assay were applied for cell growth. Transwell assay was performed for cell migration and invasion. Flow cytometry analysis was utilized for cell apoptosis. Western blot assay was conducted for the levels of apoptosis-related proteins and PDE7B protein. Dual-luciferase reporter assay was carried out to analyze the targeting relationship between miR-421 and circ_WWC3 or PDE7B. The murine xenograft model was established to explore the effect of circ_WWC3 in vivo . Results Compared to normal tissues and cells, circ_WWC3 and PDE7B were downregulated in OS tissues and cells. Overexpression of circ_WWC3 or PDE7B suppressed OS cell growth, migration, and invasion and promoted apoptosis in vitro . Regarding the mechanism analysis, circ_WWC3 positively modulated PDE7B expression by targeting miR-421. MiR-421 overexpression restored the impacts of circ_WWC3 on OS cell growth, metastasis, and apoptosis. Inhibition of miR-421 repressed the malignant behaviors of OS cells by targeting PDE7B. In addition, circ_WWC3 inhibited the tumorigenicity of OS in vivo . Conclusion Circ_WWC3 overexpression slowed the development of OS by elevating PDE7B via sponging miR-421.

The aim of this study was to investigate the detailed role and molecular mechanism of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in cardiac hypertrophy. Cardiac hypertrophy was established by transverse abdominal aortic constriction (TAC) in vivo or angiotensin II (Ang II) treatment in vitro . Levels of lncRNA TUG1, miR-497 and myocyte enhancer factor 2C (MEF2C) mRNA were assessed by quantitative reverse transcriptase PCR (qRT-PCR). Western blot assay was performed to determine the expression of MEF2C protein. The endogenous interactions among TUG1, miR-497 and MEF2C were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that TUG1 was upregulated and miR-497 was downregulated in the TAC rat model and Ang II-induced cardiomyocytes. TUG1 knockdown or miR-497 overexpression alleviated the hypertrophy induced by Ang II in cardiomyocytes. Moreover, TUG1 acted as a sponge of miR-497, and MEF2C was directly targeted and repressed by miR-497. miR-497 overexpression mediated the protective role of TUG1 knockdown in Ang II-induced cardiomyocyte hypertrophy. MEF2C was a functional target of miR-497 in regulating Ang II-induced cardiomyocyte hypertrophy. In addition, TUG1 regulated MEF2C expression through sponging miR-497. Knockdown of TUG1 rescued Ang II-induced hypertrophy in cardiomyocytes at least partly through targeting the miR-497/MEF2C axis, highlighting a novel promising therapeutic target for cardiac hypertrophy treatment.

Background Acute pancreatitis (AP) is a common inflammatory disorder. MicroRNAs play crucial roles in the pathogenesis of AP. In this article, we explored the detailed role and molecular mechanisms of miR-146b-3p in AP progression. Methods The rat AR42J cells were treated with cerulein to establish the AP model in vitro . The miR-146b-3p and Annexin A2 (Anxa2) mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were tested using the Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Caspase-3 activity and the production of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay and qRT-PCR. Targeted interaction between miR-146b-3p and Anxa2 was verified by the dual-luciferase reporter and RNA immunoprecipitation assays. Western blot analysis was performed to detect the expression of Anxa2 protein. Results Our data revealed that miR-146b-3p was significantly downregulated in AP samples. The enforced expression of miR-146b-3p alleviated cerulein-induced injury in AR42J cells, as evidenced by the promotion in cell viability and the repression in cell apoptosis, as well as the reduction in IL-1β, IL-6, and TNF-α production. Anxa2 was directly targeted and inhibited by miR-146b-3p. Moreover, the alleviative effect of miR-146b-3p overexpression on cerulein-induced AR42J cell injury was mediated by Anxa2. Conclusions The current work had led to the identification of miR-146b-3p overexpression that protected against cerulein-induced injury in AR42J cells at least in part by targeting Anxa2, revealing a promising target for AP diagnosis and treatment.

Gastric cancer (GC) is ranked the fourth leading cause of cancer-related death, with an over 75% mortality rate worldwide. In recent years, miR-299-3p has been identified as a biomarker in multiple cancers, such as acute promyelocytic leukemia, thyroid cancer, and lung cancer. However, the regulatory mechanism of miR-299-3p in GC cell progression is still largely unclear. Cell viability and apoptosis tests were performed by CCK8 and flow cytometry assay, respectively. Transwell assay was recruited to examine cell invasion ability. The interaction between miR-299-3p and PAX3 was determined by the luciferase reporter system. PAX3 protein level was evaluated by western blot assay. The expression of miR-299-3p was downregulated in GC tissues and cell lines (MKN-45, AGS, and MGC-803) compared with the normal tissues and cells. Besides, overexpression of miR-299-3p significantly suppressed proliferation and invasion and promoted apoptosis in GC. Next, we clarified that PAX3 expression was regulated by miR-299-3p using a luciferase reporter system, qRT-PCR, and western blot assay. Additionally, downregulation of PAX3 repressed GC cell progression. The rescue experiments indicated that restoration of PAX3 inversed miR-299-3p-mediated inhibition on cell proliferation and invasion. miR-299-3p suppresses cell proliferation and invasion as well as induces apoptosis by regulating PAX3 expression in GC, representing desirable biomarkers for GC diagnosis and therapy.

Several factors are linked with a higher risk of mortality from Coronavirus disease-19 (COVID-19), including male gender, increased age, hypertension, diabetes mellitus, obesity, cardiovascular diseases, chronic obstructive pulmonary disease, and cancer. Hyperglycemic COVID-19 patients have severe clinical problems, increased ICU admittance, machine-driven ventilation, and a substantial rise in inflammatory markers. Among all patients, those with diabetes or hyperglycemia have a two- to four-fold increase in mortality and severity of COVID-19 than those without diabetes. The primary cause of mortality in COVID-19 patients with diabetes is compromised immune response to viral infections. Increased blood sugar level probably affects intracellular degradation of bacteria, neutrophil chemotaxis, and phagocytosis, thus improving viral binding affinity and entry and decreasing virus clearance. In addition, it has significant effects on the proteins by inducing glycosylation and altering the composition of complements, and glycosylation renders cells susceptible to viral inflammation and damage. The treatment of COVID-19 in patients with diabetes requires an integrated team approach to minimize the risk of medical complications and mortality. Moreover, physicians should adopt proactive strategies to care for persons with comorbidities. This strategy would help reduce the frequency of complications and mortality among patients and load on the healthcare system.

Numerous inhibitors of tyrosine-protein kinase KIT, a receptor tyrosine kinase, have been explored as a viable therapy for the treatment of gastrointestinal stromal tumor (GIST). However, drug resistance due to acquired mutations in KIT makes these drugs almost useless. The present study was designed to screen the novel inhibitors against the activity of the KIT mutants through pharmacophore modeling and molecular docking. The best two pharmacophore models were established using the KIT mutants’ crystal complexes and were used to screen the new compounds with possible KIT inhibitory activity against both activation loop and ATP-binding mutants. As a result, two compounds were identified as potential candidates from the virtual screening, which satisfied the potential binding capabilities, molecular modeling characteristics, and predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Further molecular docking simulations showed that two compounds made strong hydrogen bond interaction with different KIT mutant proteins. Our results indicated that pharmacophore models based on the receptor–ligand complex had excellent ability to screen KIT inhibitors, and two compounds may have the potential to develop further as the future KIT inhibitors for GIST treatment. Graphical abstract

TEA domain family members (TEADs) play important roles in tumor progression. Till now, the genomic status of TEADs in patients with glioma has not been well investigated. To confirm whether the genomic status of TEADs could affect the prognosis of patients with glioma, the copy number variation (CNV), mutation and expression data of glioma cohorts in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas were comprehensively analyzed. Results showed that TEAD CNV frequency in lower grade gliomas (LGGs) was higher than in glioblastoma multiforme (GBM). Multivariate cox regression analysis showed that TEAD4 CNV increase was significantly associated with overall survival (OS) and disease-free survival (DFS) in LGGs (OS p = 0.022, HR = 1.444, 95% CI: 1.054–1.978; DFS p = 0.005, HR = 1.485, 95% CI: 1.124–1.962), while not in GBM. Patients with TEAD4 CNV increase showed higher expression level of TEAD4 gene. In LGG patients with IDH mutation, those with higher TEAD4 expression levels had shorter OS and DFS. Integrating TEAD4 CNV increase, IDH mutations, TP53 mutation, ATRX mutation and 1p19q co-deletion would separate patients with LGG into four groups with significant differences in prognosis. These study results suggested that TEAD4 variations were independent predictive biomarkers for the prognosis in patients with LGG with IDH mutation.

Renal cell carcinoma (RCC) is a common urological malignancy. Circular RNAs (circRNAs) have been confirmed to play an important regulatory role in various cancers. This study aimed to investigate the role and potential mechanism of circTLK1 (hsa_circ_0004442) in RCC. The levels of circTLK1, Cbl proto-oncogene (CBL), and microRNA-495-3p (miR-495-3p) were detected by quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation, cycle arrest and apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, scratch, and transwell assays. The levels of E-cadherin and Vimentin were measured by western blot. The targeting relationship between miR-495-3p and miR-495-3p or CBL was verified by dual-luciferase reporter assay. Tumor growth in vivo was evaluated by xenograft assay. The results found that circTLK1 and CBL were up-regulated in RCC tissues and cells. Silencing of circTLK1 or CBL inhibited proliferation and metastasis and accelerated apoptosis in RCC cells. In addition, circTLK1 directly bound to miR-495-3p, and CBL was the target of miR-495-3p. circTLK1 sponged miR-495-3p to increase CBL expression. Moreover, knockdown of circTLK1 suppressed tumor growth in vivo . In conclusion, down-regulation of circTLK1 restrained proliferation and metastasis and promoted apoptosis in RCC cells by modulating miR-495-3p/CBL axis.

Background Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during the surgical treatment. Emerging evidence indicates a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exerts a protective effect on LSECs. Methods We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO 2 , and 95% N 2 ), followed by glucose-free Dulbecco’s modified Eagle’s medium (DMEM) medium for 6 h and high glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated, and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress, and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly downregulated both mRNA and protein levels of CXCR4, followed by the rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways. Conclusions miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.

Osteoarthritis (OA) is a common chronic joint disease. This study aimed to explore the function of long noncoding RNA taurine-upregulated gene 1 (TUG1) in the progression and initiation of OA. Levels of TUG1, microRNA-320c (miR-320c) and fucosyltransferase 4 (FUT4) were examined via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide and flow cytometry assays were used to detect cell viability and apoptosis, respectively. The expression of relative proteins was measured using Western blot. The interaction between miR-320c and TUG1 or FUT4 was confirmed utilizing dual-luciferase reporter and RNA immunoprecipitation assays. In this study, levels of TUG1 and FUT4 were distinctly upregulated, but miR-320c level significantly decreased in OA tissues and chondrocytes derived from OA tissues as well as in IL-1β-stimulated C28/I2 cells. Mechanically, TUG1 sponged miR-320c and miR-320c targeted FUT4. In addition, TUG1 knockdown accelerated cell proliferation and repressed apoptosis and extracellular matrix (ECM) degradation in IL-1β-induced C28/I2 cells, whereas these effects of TUG1 deletion were rescued by either miR-320c inhibitor or FUT4 upregulation. Meanwhile, TUG1 sponged miR-320c to regulate FUT4 expression in IL-1β-induced C28/I2 cells. Collectively, TUG1 modulated cell proliferation, apoptosis and ECM degradation in IL-1β-induced C28/I2 cells via the miR-320c/FUT4 axis, providing a new insight into the OA treatment.

Background Duodenal adenocarcinoma (DA) with skin metastasis as initial manifestation is clinically rare. In this study, we report a rare case of skin metastasis of DA. Case presentation An 84-year-old male patient developed multiple ecchymoses on the trunk and lower extremities. Physical examination showed that the ecchymosis was dark red and had a hard texture, but showed no bulging, rupture, or tenderness. The skin biopsy implied skin metastatic adenocarcinoma. After an endoscopic duodenal biopsy, the patient was finally diagnosed with DA with skin metastasis. The patient received two courses of oral treatment of Tegafur (40 mg, bid d1–d14). However, the patient stopped taking Tegafur because of its poor effect and received Chinese medicine as a replacement treatment. Unfortunately, he was lost to follow-up. Conclusions Early diagnosis of DA metastasis is of significant importance as prognosis of these patients is poor.

In this study, we aimed to observe the effects of Loofah cylindrica (LC) extract on learning and memory ability, brain tissue morphology, and immune function of aging mice. Kunming mice were selected and randomly divided into a control group, a positive control group, an aging group, and three dose groups. Three dose groups were administered 187.5, 375, and 750 mg/kg of LC extract, respectively. Except for the control group, the mice in any other group were continuously subcutaneously injected d -galactose on the back and neck. Platform tests and Morris water maze (MWM) were adopted to test the learning and memory ability of each group. The brain index, thymus index, and spleen index of each group were determined by the organ-to-body ratio method. The enzyme-linked immunosorbent assay was performed to measure the concentration of cytokines interleukin 2 and interferon gamma and the proliferation activity of T lymphocytes in mouse serum. In addition, the hematoxylin and eosin staining was employed to observe the morphological changes in mouse brain tissues of each group. The results show that the aging group made more errors in the platform test, had longer escape latency, shorter swimming time in the platform quadrant, and fewer platform crossings in the MWM; much fewer brain tissue cells; and smaller brain index, thymus index, and spleen index. The LC extracts (375 and 750 mg/kg) can significantly antagonize the changes in the above indices. It can be concluded that LC extract can improve the learning and memory of aging mice, enhance their immune activity, and delay the aging process.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and stands among the leading causes of cancer-related deaths. Although deregulation of the microbiota in the gastrointestinal tract has been frequently described in CRC, very little is known about the precise molecular mechanisms by which bacteria and their toxins modulate the process of tumorigenesis and behavior of cancer cells. In this study, we produced recombinant Bacteroides fragilis enterotoxin-1 (rBFT1) and demonstrate that rBFT1 could promote cell proliferation in colorectal cancer cells and accelerate tumor growth in vivo . To identify the mechanisms, we further investigated CCL3/CCR5 and NF-κB pathway. We found that CCL3, CCR5, NF-κB, and TRAF-6 were dramatically upregulated after rBFT1 treatment, thus suggesting that the role of rBFT1 in CRC progression may be associated with CCL3/CCR5 and NF-κB pathways. Collectively, our results indicate that rBFT1 serves as a tumor promoter and plays a crucial role in inducing the proliferation of CRC via accelerating CCL3-related molecular pathway, thus giving insights into mechanistic underpinnings for the prevention and treatment of CRC.

The circ_UBR4 (hsa_circ_0010283) is a novel abnormally overexpressed circRNA in oxidized low-density lipoprotein (ox-LDL)-induced model of atherosclerosis (AS) in human vascular smooth muscle cells (VSMCs). However, its role in the dysfunction of VSMCs remains to be further investigated. Here, we attempted to explore its role in ox-LDL-induced excessive proliferation and migration in VSMCs by regulating Rho/Rho-associated coiled-coil containing kinase 1 (ROCK1), a therapeutic target of AS. Expression of circ_UBR4 and ROCK1 was upregulated, whereas miR-107 was downregulated in human AS serum and ox-LDL-induced VSMCs. Depletion of circ_UBR4 arrested cell cycle, suppressed cell viability, colony-forming ability, and migration ability, and depressed expression of proliferating cell nuclear antigen and matrix metalloproteinase 2 in VSMCs in spite of the opposite effects of ox-LDL. Notably, ROCK1 upregulation mediated by plasmid transfection or miR-107 deletion could counteract the suppressive role of circ_UBR4 knockdown in ox-LDL-induced VSMCs proliferation, migration, and cell cycle progression. In mechanism, miR-107 was identified as a target of circ_UBR4 to mediate the regulatory effect of circ_UBR4 on ROCK1. circ_UBR4 might be a contributor in human AS partially by regulating VSMCs’ cell proliferation, migration, and cell cycle progression via circ_UBR4/miR-107/ROCK1 pathway.

A new approach is adopted to treat primary immunodeficiency disorders, such as the severe combined immunodeficiency (SCID; e.g., adenosine deaminase SCID [ADA-SCID] and IL-2 receptor X-linked severe combined immunodeficiency [SCID-X1]). The success, along with the feasibility of gene therapy, is undeniable when considering the benefits recorded for patients with different classes of diseases or disorders needing treatment, including SCID-X1 and ADA-SCID, within the last two decades. β-Thalassemia and sickle cell anemia are two prominent monogenic blood hemoglobin disorders for which a solution has been sought using gene therapy. For instance, transduced autologous CD34+ HSCs via a self-inactivating (SIN)-Lentivirus (LV) coding for a functional copy of the β-globin gene has become a feasible procedure. adeno-associated virus (AAV) vectors have found application in ocular gene transfer in retinal disease gene therapy (e.g., Leber’s congenital amaurosis type 2), where no prior treatment existed. In neurodegenerative disorders, successes are now reported for cases involving metachromatic leukodystrophy causing severe cognitive and motor damage. Gene therapy for hemophilia also remains a viable option because of the amount of cell types that are capable of synthesizing biologically active FVIII and FIX following gene transfer using AAV vectors in vivo to correct hemophilia B (FIX deficiency), and it is considered an ideal target, as proven in preclinical studies. Recently, the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 gene-editing tool has taken a center stage in gene therapy research and is reported to be efficient and highly precise. The application of gene therapy to these areas has pushed forward the therapeutic clinical application.

Background Glioma is the most frequent, highly aggressive primary intracranial malignant tumor. Circular RNA (circRNA) circ_0037655 has been reported to be a vital regulator in glioma. The different functional mechanism behind circ_0037655 was investigated in the current study. Methods The expression of circ_0037655, microRNA-1229-3p (miR-1229-3p) and integrin beta-8 (ITGB8) was detected via the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular research was performed via colony formation assay for cell proliferation, flow cytometry for cell cycle and cell apoptosis, scratch assay for cell migration, as well as transwell assay for cell migration and invasion. Western blot was used for detection of ITGB8 protein and epithelial–mesenchymal transition (EMT) process. Dual-luciferase reporter assay was implemented for the binding analysis of potential targets. In vivo assay was administered via xenograft in mice. Results Upregulation of circ_0037655 was affirmed in glioma samples and cells. Tumor formation and metastasis of glioma were inhibited after circ_0037655 was downregulated. miR-1229-3p acted as a target of circ_0037655, and its upregulation was responsible for the function of si-circ_0037655 in glioma cells. miR-1229-3p functioned as a tumor inhibitor in glioma progression by targeting ITGB8. circ_0037655 modulated the ITGB8 expression by targeting miR-1229-3p. In vivo knockdown of circ_0037655 also suppressed glioma tumorigenesis by acting on the miR-1229-3p/ITGB8 axis. Conclusion This study showed that downregulation of the expression of circ_0037655 could inhibit glioma progression by acting on the miR-1229-3p/ITGB8 axis. The specific circ_0037655/miR-1229-3p/ITGB8 axis was disclosed in glioma research.

This study aims to assess vitamin D deficiency-induced dyslipidemia and cardiovascular disease (CVD) risk in poor glycemic control among type 2 diabetes mellitus (T2DM) patients. This study was carried out among 455 T2DM patients involving poor glycemic control ( n = 247) and good glycemic control ( n = 208). Fasting plasma glucose (FPG) and HbA 1 c were measured to assess glycemic control. Cardiac risk ratio, atherogenic index plasma, and atherogenic coefficient were calculated to assess and compare the CVD risk in different groups. Patients with poor control had a significantly higher level of total cholesterol (TC), triglyceride (TG), and non-high-density lipoprotein lipase cholesterol (non-HDL-C), atherogenic variables, and lower level of high-density lipoprotein lipase cholesterol (HDL-C) as compared to patients with good glycemic control. We also observed significant negative correlation of vitamin D with lipid markers and atherogenic variables in poor glycemic control diabetic population. The serum vitamin D levels were inversely associated with HbA 1 c, FPG, TG, TC, and non-HDL-C. Furthermore, hypercholesterolemia, hypertriglyceridemia, and elevated non-HDL-C were the independent risks in hypovitaminosis D population. Vitamin D deficiency in poor glycemic control is likely to develop dyslipidemia as compared to vitamin D insufficient and sufficient groups. Thus, vitamin D supplementation and an increase in exposure to sunlight may reduce the risk of cardiovascular complications in diabetes.

Background Circular RNAs play crucial roles in tumor occurrence and progression. This research aimed to explore the role and potential mechanism of hsa_circ_0013359 (circ_0013359) in melanoma. Methods The levels of circ_0013359, microRNA-136-5p (miR-136-5p), and member RAS oncogene family (RAB9A) in melanoma tissues and cells were detected using quantitative reverse transcriptase-polymerase chain reaction or western blot. Cell proliferation, apoptosis, cell cycle, cell migration, and invasion were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide assay, colony formation assay, flow cytometry, and transwell assay. Glycolysis was determined by detecting glucose consumption, lactate production, and extracellular acidification rate. The levels of hexokinase 2 and lactate dehydrogenase A were examined by western blot. The targeting relationship between miR-136-5p and circ_0013359 or RAB9A was confirmed by dual-luciferase reporter assay. Xenograft experiments were used to analyze tumor growth in vivo . Results Circ_0013359 and RAB9A levels were increased, while the miR-136-5p level was reduced in melanoma tissues and cells. Circ_0013359 knockdown inhibited proliferation, migration, invasion, and glycolysis and promoted apoptosis and cycle arrest in A875 and SK-MEL-1 cells. Circ_0013359 sponged miR-136-5p to regulate melanoma progression. In addition, miR-136-5p suppressed melanoma progression by targeting RAB9A. Besides, circ_0013359 silencing inhibited tumor growth in vivo . Conclusion Depletion of circ_0013359 hindered melanoma progression by regulating miR-136-5p/RAB9A axis.

Background The purpose of the study was to explore the precise parts of circ_0066147 (circular RNA [circRNA] scm-like with four mbt domains 1, circSFMBT1) in pancreatic cancer (PC) progression. Methods Ribonuclease R assay was used to confirm the stability of circ_0066147. circ_0066147, miR-326 and E2F transcription factor 2 (E2F2) expression levels was detected by quantitative reverse-transcription polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion abilities were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H -tetrazolium bromide, flow cytometry, wound-healing and transwell assays, respectively. Targeted relationships among circ_0066147, miR-326 and E2F2 were verified by the dual-luciferase reporter or RNA pull-down assay. Results circ_0066147 expression was upregulated in PC tissues and cells. circ_0066147 knockdown inhibited PC cell proliferation, migration, invasion and enhanced apoptosis in vitro , as well as weakened tumor growth in vivo . Mechanistically, circ_0066147 directly targeted miR-326 and circ_0066147 modulated E2F2 expression by miR-326. miR-326 mediated the regulation of circ_0066147 in PC cell behaviors in vitro . Furthermore, E2F2 was a functional target of miR-326 in modulating PC cell behaviors in vitro . Conclusion circ_0066147 regulated PC malignant progression in part depending on the miR-326/E2F2 axis, illuminating circ_0066147 was a potential prognostic marker and therapeutic target for PC management.

Long noncoding RNA (lncRNA) has been shown to be involved in the development of osteoarthritis (OA), an age-related bone and joint disease. However, the function and possible molecular mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in lipopolysaccharide (LPS)-induced chondrocytes injury model remain unexplored. Cell viability and apoptosis were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Western blot was used to detect protein expression. The concentrations of inflammatory factors were estimated by enzyme-linked immunosorbent assay (ELISA). Abundances of MIAT, microRNA-488-3p (miR-488-3p), and sex determining region Y-related HMG-box 11 (SOX11) were examined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to analyze the interaction between miR-488-3p and MIAT or SOX11. LPS caused chondrocytes injury by reducing cell activity and increasing apoptosis rate and inflammatory factor secretions. Higher levels of MIAT and SOX11 and lower miR-488-3p were observed in LPS-treated C28/I2 cells. Importantly, knockdown of MIAT attenuated the LPS-induced cell injury by targeting miR-488-3p, and miR-488-3p overexpression weakened the LPS-induced cell injury by targeting SOX11. Additionally, repression of MIAT inactivated the LPS-induced NF-κB signaling pathway by decreasing SOX11 and increasing miR-488-3p. Knockdown of MIAT alleviated the LPS-induced chondrocytes injury by inhibiting the NF-κB signaling pathway mediated by the miR-488-3p/SOX11 axis.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo . circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.

lncRNA–mRNA co-expression pairs and prognostic markers related to the development of laryngeal squamous cell carcinoma (LSCC) were investigated. The lncRNA and mRNA expression data of LSCC in GSE84957 and RNA-seq data of 112 LSCC samples from TCGA database were used. Differentially expressed genes (DEGs) and lncRNAs (DE-lncRNAs) between LSCC and para-cancer tissues were identified. Co-expression analysis of DEGs and DE-lncRNA was conducted. Protein–protein interaction network for co-expressed DEGs of top 25 DE-lncRNA was constructed, followed by survival analysis for key nodes in co-expression network. Finally, expressions of several DE-lncRNAs and DEGs were verified using qRT-PCR. The lncRNA–mRNA network showed that ANKRD20A5P, C21orf15, CYP4F35P, LOC_I2_011146, XLOC_006053, XLOC_I2_003881, and LOC100506027 were highlighted in network. Some DEGs, including FUT7, PADI1, PPL, ARHGAP40, MUC21, and CEACAM1, were co-expressed with above lncRNAs. Survival analysis showed that PLOD1, GLT25D1, and KIF22 were significantly associated with prognosis. qRT-PCR results showed that the expressions of MUC21, CEACAM1, FUT7, PADI1, PPL, ARHGAP40, ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, LOC_I2_011146, and XLOC_006053 were downregulated, whereas the expression of LOC100506027 was upregulated in LSCC tissues. PLOD1, GLT25D1, and KIF22 may be potential prognostic markers in the development of LSCC. C21orf15-MUC21/CEACAM1/FUT7/PADI1/PPL/ARHGAP40 are potential lncRNA–mRNA pairs that play significant roles in the development of LSCC. Graphical abstract Several genes, PLOD1, GLT25D1, and KIF22, are identified as potential prognostic markers for LSCC development. In addition, lncRNA–mRNA pairs related to LSCC were explored, and 6 DEGs (MUC21, CEACAM1, FUT7, PADI1, PPL, and ARHGAP40) and 7 DE-lncRNAs (ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, XLOC_I2_011146, XLOC_006053, and LOC100506027) were validated to be abnormally expressed in LSCC tissue.

Radiation inactivation of enveloped viruses occurs as the result of damages at the molecular level of their genome. The rapidly emerging and ongoing coronavirus disease 2019 (COVID-19) pneumonia pandemic prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global health crisis and an economic devastation. The readiness of an active and safe vaccine against the COVID-19 has become a race against time in this unqualified global panic caused by this pandemic. In this review, which we hope will be helpful in the current situation of COVID-19, we analyze the potential use of γ-irradiation to inactivate this virus by damaging at the molecular level its genetic material. This inactivation is a vital step towards the design and development of an urgently needed, effective vaccine against this disease.

Alcohol dehydrogenase iron containing 1 (ADHFE1) encodes a hydroxyacid-oxoacid transhydrogenase participating in multiple biological processes. The role of ADHFE1 in cancer has not been fully uncovered. Herein, we performed data analysis to investigate the expression of ADHFE1 and the underlying regulatory mechanisms, its relationship with cancer patients’ survival, and the relevant pathways in cancer. A range of recognized, web-available databases and bioinformatics tools were used in this in silico study. We found that ADHFE1 was frequently downregulated and hypermethylated in various cancer cell lines and tissue samples. High expression of ADHFE1 was positively associated with favorable patient prognosis in breast, colon, and gastric cancers. Pathway analysis revealed its potential role in cancer-related biological processes, including energy metabolism, DNA replication, and cell cycle regulation. AHDFE1 mRNA expression and DNA methylation can potentially be used as diagnostic markers in cancer and might be of great value in predicting the survival of patients with cancer.

Background The current study investigates the effect of transcription factor Prox1 on the proliferation, migration, and invasion ability of lung cancer. Methods Lung cancer cell lines (A549 and H446 cells) were transfected with Prox1NAD and siRNA, respectively. Thus, the A549 and H446 cells overexpressed Prox1 after transfection of Prox1NAD plasmids, and A549 and H446 cells have low expression of Prox1 after transfection with siRNA. Reverse transcriptase quantitative PCR and western blot analyses were used to detect Prox1 mRNA and protein expression in cells. Plate clone formation experiments and MTT experiments were used to detect cell proliferation. Western blot was used to detect the expression of Rho family-related proteins in cells. Results Compared to untransfected wild-type A549 and H446 that served as blank controls, the expression level of Prox1mRNA and protein in A549 and H446 cells overexpressing Prox1 after plasmid transfection was high, while the expression level of Prox1mRNA and protein in A549 and H446 cells with low expression of Prox1 after siRNA transfection was low. With the increase of Prox1 expression, the expression of RhoA and RhoC increased, while the expression of RhoB decreased. Conclusion The finding of this study may provide a new approach for the treatment of lung cancer using targeted gene therapy.

Autoimmune thyroid disease (AITD) is more common among diabetes mellitus (DM) patients and may impact its microvascular complications. The present study aimed to assess the relationship between AITD and the prevalence of diabetic kidney disease (DKD) in patients with diabetes mellitus type 1 (DM1). Anthropometric parameters, parameters of metabolic control of DM, thyreometabolic status, and the UACR were assessed. DKD was diagnosed if patients’ UACR level was ≥30 mg/g or eGFR level was <60 mL/min. This study involved 144 patients with DM1 aged 36.2 ± 11.7 years: 49 men and 95 women. Significant differences in creatinine, eGFR, and UACR levels were found in patients with DKD. fT3 concentration was significantly lower among DKD patients. A significantly higher probability of DKD was found in DM1 patients with lower fT3 levels. Patients with DM1 and AITD had significantly lower creatinine levels than the control group. However, the study did not show any significant relationship between AITD and the occurrence of DKD in patients with DM1. Significantly lower fT3 concentrations in DKD patients may be caused by metabolic disorders in the course of DKD and require further cohort studies in a larger population of patients with DM1 and AITD.

The purpose of this study was to investigate whether the Dictyophora echinovolvata spore polysaccharides (DESP) affect the immunity in immunocompromised mice induced by cyclophosphamide (CTX). The healthy female Kunming mice were randomly divided into six groups, including a normal control (NC) group, a positive control group, a model control (MC) group, and three groups treated with low-, intermediate-, and high-dose polysaccharide, respectively. A series of immunoregulatory properties were determined, including humoral and cellular immunity, immune function, and immune factors of mononuclear macrophages. Compared with NC and MC groups, treatment with DESP significantly increased the spleen index and decreased the thymus index; increased the serum concentrations of immunoglobulin (Ig)A, IgG, IgM, hemolysin, IL-1β, and IL-2; delayed the allergic reaction; and improved the splenic lymphocyte transformation ability; and enhanced the phagocytosis of macrophages and the ability to secrete IL-6, TNF-α, caspase-1, and NO with DESP supplementation. These results indicated that DESP might have a good regulatory effect on CTX-induced immunodeficiency in mice, adjust the body’s immune imbalance, and improve the symptoms of low immunity.

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading remarkably fast worldwide. Effective countermeasures require the rapid development of data and tools to monitor its spread and better understand immunogenic profile. However, limited information is available about the tools and target of the immune responses to SARS-CoV-2. In this study, we excogitated a new approach for analyzing phylogenetic relationships by using the whole prototype proteome sequences. Phylogenetic analysis on the whole prototype proteome sequences showed that SARS-CoV-2 was a direct descendant of Bat-CoV and was closely related to Pangolin-CoV, Bat-SL-CoV, and SARS-CoV. The pairwise comparison of SARS-CoV-2 with Bat-CoV showed an unusual replacement of the motif consisting of seven amino acids (NNLDSKV) within the spike protein of SARS-CoV-2. The replaced motif in the spike protein of SARS-CoV-2 was found in 12 other species, including a conserved surface protein of a malaria-causing pathogen, Plasmodium malariae . We further identified the T and B cell epitope sequence homology of SARS-CoV-2 spike protein with conserved surface protein of P. malariae using the Immune Epitope Database and Analysis Resource (IEDB). The shared immunodominant epitopes may provide immunity against SARS-CoV-2 infection to those previously infected with P. malariae .

Mesenchymal stem cells (MSCs) can be obtained from almost all tissues and present promising therapeutic effects for metabolic diseases. Human adipose-derived MSCs (hASCs) have recently been widely studied due to their easy access and low immunity. Thus, we intended to figure out the effects and potential mechanism of hASCs on obesity in high-fat-diet (HFD)-induced obese mice. Following 16 weeks of being fed HFD, hASCs were intravenously injected. Two weeks later, body weight, body composition, and energy expenditure were evaluated. Additionally, the phenotypes of macrophages infiltrating adipose tissue were analyzed. The results revealed that hASCs administration significantly reduced adipose tissue weight, adipocyte size, and fat mass and exerted beneficial effects in serum lipid profile. This anti-obesity effect was mediated by the increased O 2 consumption, CO 2 production, and energy expenditure, which was further evidenced by the upregulation of uncoupling protein-1 (UCP-1) and metabolism-associated genes. Furthermore, hASCs infusion increased the amount of alternatively activated (M2) macrophages in adipose tissue, and the expression of pro-inflammatory cytokines-related genes was reduced. Taken together, these results indicated that hASCs suppressed obesity by increasing UCP-1 expression and enhancing energy expenditure, and this effect might be due to the increased M2 macrophages.

Long noncoding RNA (lncRNA) highly upregulated in liver cancer (HULC) has been reported to be implicated in chemoresistance. However, the potential mechanism of HULC in paclitaxel (PTX)-resistant ovarian cancer (OC) remains undefined. The expression of RNAs and proteins was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assay. The PTX resistance and apoptotic rate were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Furthermore, the interaction between miR-137 and HULC or integrin beta-8 (ITGB8) was predicted by miRcode and starBase v2.0 and then verified by dual luciferase reporter and RNA pull-down assays. In addition, the xenograft mice model was established to explore the effects of HULC in vivo . HULC was significantly upregulated and miR-137 was downregulated in PTX-resistant OC tissues and cells. Also, the HULC depletion suppressed tumor growth and PTX resistance in PTX-treated mice. miR-137 was verified as a target of HULC and directly targeted ITGB8. And HULC knockdown downregulated ITGB8 expression by targeting miR-137. miR-137 inhibitor or ITGB8 overexpression mitigated the suppressive impacts of HULC knockdown on PTX resistance. Collectively, HULC modulated ITGB8 expression to promote PTX resistance of OC by sponging miR-137.

Background To analyze mechanisms of action of glucocorticoid treatment for endoplasmic reticulum stress (ERS) in sensorineural hearing loss (SNHL), we aimed to evaluate the expression and activation status of the protein kinase RNA-like ER kinase (PERK)–C/EBP homologous protein (CHOP) pathway, which is the major pathway in the ERS. Methods In the present study, we established an in vitro ERS model using tunicamycin-treated hair-cell-like HEI-OC1 cells. The effect of dexamethasone on proliferation inhibition, apoptosis, and ATF4–CHOP pathway in HEI-OC1 cells was examined by CCK-8 assay, flow cytometry, western blotting, and reverse transcription PCR, respectively. Results In HEI-OC1 cells, dexamethasone was shown to significantly reduce the tunicamycin-induced expression of ATF4 and CHOP in the context of sustained viability and proliferation, a therapeutic effect that was reversible by co-treatment with a glucocorticoid antagonist. Conclusion Dexamethasone can protect hair-cell-like HEI-OC1 cells from ERS damage, which may be one of the mechanisms of action for GCs in SNHL treatment.

This study investigates the ability of blood neutrophil-to-lymphocyte ratio (NLR) to predict acute organophosphorus pesticide poisoning (AOPP). Clinical data of 385 patients with AOPP were obtained within 24 h of admission, and NLR values were calculated based on neutrophil and lymphocyte counts. The patients were divided into two groups – good and poor – based on prognosis. Poor prognosis included in-hospital death and severe poisoning. The factors affecting prognosis were analyzed by logistic regression analysis, and the prognostic value of NLR was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that NLR levels, serum cholinesterase, and creatinine levels were good predictors of AOPP. Multivariate logistic regression analysis showed that high NLR was an independent risk factor for severe poisoning (adjusted odds ratio [AOR], 1.13; 95% CI, 1.10–1.17; p < 0.05) and in-hospital mortality (AOR, 1.07; 95% CI, 1.03–1.11; p < 0.05). NLR values >13 and >17 had a moderate ability to predict severe poisoning and in-hospital mortality, respectively (AUC of 0.782 [95% CI, 0.74–0.824] and 0.714 [95% CI, 0.626–0.803], respectively). Our results show that high NLR at admission is an independent indicator of poor prognosis in AOPP and can be used to optimize treatment and manage patients.

Gastric mucosal injury is caused by an imbalance between the mucosal defense and gastro-irritants, leading to gastroenteritis. Diosgenin is a steroidal sapogenin found in the wild Yam plant that has been reported with several pharmacological properties. The aim of this study is to explore the gastroprotective role of diosgenin on gastric mucosal damage caused by HCl/ethanol in rats. Male Sprague-Dawley rats were intragastrically administered with diosgenin (20 mg/kg) before HCl/ethanol (0.15 M HCl in 98 % ethanol) administration. Omeprazole was used as a positive control. Diosgenin-attenuated oxidative stress by enhancing ( p < 0.05) antioxidant enzymes, reducing lipid peroxidation (MDA), and modulating nitric oxide (NO) levels. Anti-inflammatory effects of diosgenin were observed by a reduction in pro-inflammatory cytokines ( p < 0.05), decreased myeloperoxidase (MPO) activities ( p < 0.05), and histopathological observation of gastric mucosal damage. Western blot analysis provided evidence on the downregulation of NF-κβ by diosgenin. The findings showed that diosgenin has a significant protective role on gastric injury caused by HCl/ethanol, through its antioxidant, anti-inflammatory role, and suppression of NF-κβ and MPO activities.

Osteosarcoma is the most common type of primary malignant tumor of the bone, with a high metastatic rate and poor prognosis. Therefore, it is important to further elucidate the molecular mechanisms involved in the development of osteosarcoma and explore new molecular therapeutic targets. Long intergenic nonprotein-coding RNA 707 (LINC00707) is an oncogenic gene in several cancers. In this study, we further clarified its role and regulatory mechanism in osteosarcoma. We found that LINC00707 levels are significantly higher in the osteosarcoma cell lines SW 1353, HOS, U-2 OS, MG-63, and Saos-2 compared to those in human fetal osteoblastic cell line hFOB1.19. LINC00707 silencing suppressed cell proliferation, migration, and invasion of MG-63 and Saos-2 cells. Moreover, LINC00707 can act as a competitive endogenous RNA of miR-338-3p, and miR-338-3p inhibitor and AHSA1 overexpression alleviated the effect of LINC00707 silencing. In conclusion, we demonstrated high expression of LINC00707 in osteosarcoma cell lines and that silencing LINC00707 suppresses cell proliferation, migration, and invasion by targeting the miR-338-3p/AHSA1 axis in MG-63 and Saos-2 cells. These findings suggest that LINC00707 may serve as a potential target for osteosarcoma treatment.

A 29-year-old woman presented to the emergency department with the acute onset of palpitations, shortness of breath, and haemoptysis. She reported having an abortion (56 days of pregnancy) 1 week before admission because of hyperthyroidism diagnosis during pregnancy. The first diagnoses considered were cardiomyopathy associated with hyperthyroidism, acute left ventricular failure, and hyperthyroidism crisis. The young woman’s cardiocirculatory system collapsed within several hours. Hence, venoarterial extracorporeal membrane oxygenation (VA ECMO) was performed for this patient. Over the next 3 days after ECMO was established, repeat transthoracic echocardiography showed gradual improvements in biventricular function, and later the patient recovered almost completely. The patient’s blood pressure increased to 230/130 mm Hg when the ECMO catheter was removed, and then the diagnosis of phaeochromocytoma was suspected. Computed tomography showed a left suprarenal tumour. The tumour size was 5.8 cm × 5.7 cm with central necrosis. The vanillylmandelic acid concentration was 63.15 mg/24 h. Post-operation, pathology confirmed phaeochromocytoma. To our knowledge, this is the first case report of a patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism which was successfully resuscitated by VA ECMO.

This article was designed to explore the effects and mechanisms of miR-185-5p on the replication of hepatitis C virus (HCV). Quantitative reverse transcription PCR (qRT-PCR) was performed for detecting the abundance of miR-185-5p and HCV RNA in HCV-infected primary hepatocytes and Huh7.5 cells. Dual-luciferase reporter gene assay was used for exploring the interaction between miR-185-5p and GALNT8. Western blot analyzed protein expression of GALNT8, NS3, and NS5A. miR-185-5p was remarkably downregulated in HCV-infected primary hepatocytes and Huh7.5 cells. miR-185-5p upregulation inhibited HCV RNA expression, while its inhibition promoted HCV replication. miR-185-5p induced accumulation of NS3 and NS5A in the cells. Dual-luciferase reporter gene assay verified the targeted relationship between miR-185-5p and GALNT8. In addition, the effects of overexpressing or knocking down miR-185-5p on HCV replication could be correspondingly eliminated by the overexpression or knockdown of GALNT8. miR-185-5p may target GALNT8 in JFH1-infected Huh7.5 cells and then inhibit HCV replication. miR-185-5p may be a potential target for treating HCV.

Lidocaine can inhibit the malignant development of various human cancers. Circular RNA (circRNA) dynein 1 heavy chain gene (circ_DYNC1H1) acted as a pro-cancer molecule in hepatocellular carcinoma (HCC). This study aimed to explore whether the function of lidocaine was related to the oncogenic circ_DYNC1H1 in HCC. Colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay were used for proliferation detection. Cell apoptosis was assessed by flow cytometry, and migration or invasion was determined by the transwell assay. The levels of circ_DYNC1H1, microRNA-520a-3p (miR-520a-3p), and ubiquitin-specific protease 14 (USP14) were examined using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Protein levels were measured using western blot. The binding between miR-520a-3p and circ_DYNC1H1 or USP14 was confirmed by the dual-luciferase reporter assay. In vivo assay was conducted by a xenograft model in mice. Lidocaine reduced proliferation, migration, and invasion but promoted apoptosis in HCC cells. The circ_DYNC1H1 expression was downregulated in lidocaine-treated HCC cells. The inhibitory effect of lidocaine on HCC progression was weakened after circ_DYNC1H1 overexpression. miR-520a-3p was a target of circ_DYNC1H1, and the function of lidocaine was related to the regulation of circ_DYNC1H1/miR-520a-3p axis. USP14 served as a target for miR-520a-3p, and circ_DYNC1H1 could sponge miR-520a-3p to regulate the USP14 expression. The lidocaine-induced suppression of HCC development was also achieved by mediating the miR-520a-3p/USP14 axis. In vivo assay revealed that lidocaine suppressed the tumor growth of HCC by reducing the expression of circ_DYNC1H1 to affect the levels of miR-520a-3p and USP14. Our results clarified that lidocaine impeded tumor progression via targeting the circ_DYNC1H1/miR-520a-3p/USP14 axis in HCC cells.

Primary skin amyloidosis is a chronic skin disease in which amyloid deposits in the normal skin tissues without involving other organs. At present, the causes and mechanisms of morbidity have not been fully elucidated. There are few clinical reports of nodular skin amyloidosis, and the domestic reports are mostly limited cases. This study reported a rare case of a 46-year-old woman with primary localized cutaneous nodular amyloidosis (PLCNA). The patient presented with features of lymphatic malformation, a plexiform nodule of small blisters. Histological examination revealed amyloid deposits involving the superficial and deep dermis with a small number of plasma cells. Further examinations did not reveal evidence of systemic involvement, indicating a PLCNA. The presentation as lymphatic malformation lesions illustrates the importance of clinical pathology. Nodular amyloidosis typically manifests as single or multiple yellow-brown nodules or plaques of a few millimeters to several centimeters. The center of the nodule sometimes shows atrophy and relaxation or forms a bullous. It is recommended to perform a pathological examination to confirm the diagnosis to distinguish it from lymphatic malformation.

Wilson’s disease (WD) is an inherited disorder of copper metabolism. Multimodal magnetic resonance imaging (MRI) has been reported to provide evidence of the extent and severity of brain lesions. However, there are few studies related to the diagnosis of WD with multimodal MRI. Here, we reported a WD patient who was subjected to Sanger sequencing, conventional MRI, and multimodal MRI examinations, including susceptibility-weighted imaging (SWI) and arterial spin labeling (ASL). Sanger sequencing demonstrated two pathogenic mutations in exon 8 of the ATP7B gene. Slit-lamp examination revealed the presence of Kayser–Fleischer rings in both eyes, as well as low serum ceruloplasmin and high 24-h urinary copper excretion on admission. Although the substantia nigra, red nucleus, and lenticular nucleus on T1-weighted imaging and T2-weighted imaging were normal, SWI and ASL showed hypointensities in these regions. Besides, decreased cerebral blood flow was found in the lenticular nucleus and the head of caudate nucleus. The patient recovered well after 1 year and 9 months of follow-up, with only a Unified Wilson Disease Rating Scale score of 1 for neurological symptom. Brain multimodal MRI provided a thorough insight into the WD, which might make up for the deficiency of conventional MRI.

Inflammation and coagulation are considered to the development of Coronavirus disease 2019 (COVID-19)-related hypoxemia. However, this is still controversial, which brings challenges to clinical treatment. Here, we reviewed the levels of interleukin-6 (IL-6), coagulation indexes, and clinical manifestations of a patient with severe COVID-19 after Tocilizumab administration. In this case, the patient’s body temperature quickly dropped to normal after using Tocilizumab, while C reactive protein progressively decreased and stabilized at a lower level. However, IL-6 and D-dimers increased and were accompanied by a continuous decrease of the oxygenation index. After anticoagulant therapy with heparin, D-dimer decreased slowly, gradually improving the oxygenation index and disease remission. This case suggests that the formation of microthrombus might be the main reason for COVID-19-derived hypoxemia. However, the mechanism of hypoxemia and the role of Tocilizumab in COVID-19 need further research. Nevertheless, these findings might still assist medical workers in formulating timely treatment strategies for similar severe patients.

The benefit of immunochemotherapy in treating resectable locally advanced non-small cell lung cancer (NSCLC) is not well established. Here, we report a case of resectable stage III NSCLC treated with neoadjuvant immunotherapy combined with chemotherapy before surgery. A 61 years old man was admitted to our hospital due to paroxysmal cough and was diagnosed as squamous cell carcinoma T4N2M0 in the upper lobe of the right lung, which was locally advanced and resectable. He was treated with 3 courses of paclitaxel 250 mg intravenous (IV), carboplatin 0.65 g IV, and durvalumab 620 mg IV followed by thoracoscopic upper lobectomy and lymph node dissection. There was considerable regression of the tumor before surgery, and the patient achieved a complete pathological response after surgery. Our case study demonstrates the benefit of durvalumab and chemotherapy in the treatment of resectable locally advanced NSCLC.

Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood–brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.

The present research was designed to examine the effects of disintegrin metalloproteinases 10 (ADAM10) on the doxorubicin (DOX)-induced dilated cardiomyopathy (DCM) and the mechanisms involved, with a focus on ADAM10-dependent cleavage of N-cadherin. The present study constructed recombinant lentiviral vectors expressing short hairpin RNA (shRNA) targeting the ADAM10 gene. H9C2 cells were treated with the recombinant lentivirus or GI254023 (an ADAM10 inhibitor). The expression level of N-cadherin and its C-terminal fragment1 (CTF1) was tested by western blotting and flow cytometry. The adhesion ability was analyzed using a plate adhesion model. Cardiac function and morphology were assessed in control and lentivirus-transfected rats with or without DOX treatment. The inhibition of ADAM10 activity significantly increased the expression of full-length N-cadherin on the cellular surface and reduced CTF1 generation in vivo and in vitro . The adhesion ability was also increased in ADAM10-knockdown H9C2 cells. Furthermore, DOX-induced myocardial dysfunction was ameliorated in rats transfected with ADAM10-shRNA lentivirus. These findings demonstrated that ADAM10 specifically cleaves N-cadherin in cardiomyocytes. ADAM10-induced N-cadherin cleavage results in changes in the adhesive behavior of cells. Therefore, ADAM10 may serve as a therapeutic target to reverse cardiac remodeling in DCM.

Collision breast tumors, consisting of breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), are extremely rare. Here we report the case of a 64-year-old woman with a collision tumor in her left breast mass that was composed of invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia. In addition, we reviewed the published comparable English-language literature. Collision breast tumor composed of BC and NHL is extremely rare. For that reason, there is a lack of consensus about the underlying mechanism, and diagnosing it without delay remains a complex clinical challenge. We found that post-menopausal, age-related estrogen levels changes and Epstein-Barr virus infection are possible pathogenic factors. However, the symptoms are almost identical, and it is difficult to distinguish a simple breast tumor from a breast collision tumor. In this study, we reviewed the clinical features of all patients with BC and NHL colliding breast tumors; this information might enable early identification and prevention of misdiagnosis.

Type 2 diabetes mellitus (T2DM) is known as a risk factor for coronary in-stent restenosis (ISR) in patients with coronary artery disease (CAD). Evidence suggests that B cells play a functional role in the progression of atherosclerotic lesions. However, the B cell receptor (BCR) repertoire in patients with ISR remains unclear. This study aims to profile the BCR repertoire in patients with coronary ISR/T2DM. A total of 21 CAD patients with or without ISR/T2DM were enrolled. PBMCs were isolated and examined for BCR repertoire profiles using DNA-seq. Our results showed that the diversity of amino acid sequences in ISR DM patients was higher than that in ISR −DM patients. The frequencies of 21 V/J paired genes differed between ISR DM and −ISR DM patients, while frequencies of 5 V/J paired genes differed between ISR DM and ISR −DM. The −ISR −DM group presented the highest clonotype overlap rate, while ISR DM patients presented the lowest overlap rate. Our study presented the BCR repertoires in patients with ISR/T2DM. The data suggested different BCR signatures between patients with ISR and T2DM. Further analysis of BCR profiles would enhance understanding of ISR.

The recurrence rate of lymphoma is very high, and tumor stem cells may be an important mechanism. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can inhibit antitumor immunity and promote cancer progression, but its role and mechanism in lymphoma are still unclear. Here we collected lymphoma tissue and peripheral blood from patients with diffuse large B-cell lymphoma (DLBCL). Results showed that CTLA-4 expression and CD44+ cell in the high-risk group were significantly higher than that in the low-risk group. Correlation analysis showed that CTLA-4 expression positively correlated with CD44+ cell in lymphoma tissue and regulatory T (Treg) cells in lymphocytes. In vitro experiment showed that CTLA-4 increased the ratio of lymphoma stem cells, and proliferation and invasion of lymphoma cells through TGF-β pathway. Moreover, CTLA-4 enhanced the proliferation of Treg cells induced by lymphoma cells. Animal experiments showed that CTLA-4 can promote transplanted lymphoma growth. Immunohistochemistry results showed that both Ki-67 and CD44+ cells increased significantly in the CTLA-4 group. TGF-β neutralization can significantly block these effects of CTLA-4. In conclusion, CTLA-4 promoted DLBCL progression through lymphoma stem cell enrichment and immunosuppression.

Colon cancer (CRC) is a common type of cancer and has a high incidence worldwide. Protein 74 (WDR74), which consists of the WD repetition sequence, has been previously associated with tumor tumorigenesis. However, its mechanism of action in CRC remains unclear. Here, we found that WDR74 expression was upregulated in CRC tissues and cells. Downregulation of WDR74 repressed the proliferation and cell cycles in CRC cells. In addition, WDR74 knockdown induced cell apoptosis and suppressed both cell metastasis and invasion. Mechanistically, WDR74 decreased the phosphorylation of β-catenin and induced nuclear β-catenin accumulation, activating the Wnt/β-catenin signaling pathway in CRC cells. Further investigation showed that blocking the Wnt/β-catenin signaling pathway by XAV-939 reversed the effects of WDR74 on cell proliferation, migration, and invasion in HCT116 cells. Overall, WDR74 induced β-catenin translocation to the nucleus and activated the Wnt/β-Catenin, thus facilitated CRC cell proliferation and metastasis. In summary, WDR74 could be a potential target for the intervention of CRC.

Immunoglobulin γ-1 heavy chain constant region (IGHG1) is a functional isoform of immunoglobulins and plays an important role in the cytolytic activity of immune effector cells. Dysregulated IGHG1 was implicated in the occurrence and development of various tumors. Protoporphyrin IX (PpIX) is an endogenous fluorophore and is used in photodynamic therapy, which induces the generation of reactive oxygen species to initiate the death of tumor cells. However, the roles of IGHG1 in the colorectal cancer cell proliferation and PpIX accumulation have not been reported yet. Data from qRT-PCR and western blot analysis showed that IGHG1 was up-regulated in the colorectal cancer cells. Colorectal cancer cells were then transfected with shRNA targeting IGHG1 to down-regulate IGHG1 and conducted with Cell Counting Kit 8 (CCK8) and colony formation assays. Results demonstrated that shRNA-mediated down-regulation of IGHG1 decreased cell viability of colorectal cancer and suppressed cell proliferation. Moreover, PpIX accumulation was promoted and the hemin content was decreased by the silence of IGHG1. Interference of IGHG1 reduced the phosphorylated extracellular signal-regulated kinase (ERK) and ferrochelatase (FECH) expression, resulting in retarded cell proliferation in an MEK-FECH axis-dependent pathway.

Curcumin has been demonstrated to be an anti-tumor agent in many types of cancers, including gastric cancer (GC). However, the molecular mechanisms by which curcumin performs its anti-tumor effects remain elusive. circ_0056618 and miR-194-5p are reported to be involved in GC progression, but their relationships with curcumin are unclear. In this study, circ_0056618 was elevated, and miR-194-5p was reduced in GC tissues and cells. Curcumin treatment led to a decrease in circ_0056618 level in GC cells. Overexpression of circ_0056618 promoted cell proliferation, migration, and invasion and suppressed cell cycle arrest and apoptosis in curcumin-treated GC cells. Moreover, miR-194-5p was identified as the target of circ_0056618, and its expression in GC cells increased after curcumin treatment. Overexpression of miR-194-5p reversed the promotional effect of circ_0056618 on cell progression in curcumin-treated GC cells. Additionally, curcumin treatment repressed the tumorigenesis of GC in vivo through regulating circ_0056618. Curcumin treatment delayed the development of GC partly through decreasing circ_0056618 and increasing miR-194-5p.

Scutellarin plays an anti-tumor role in A549 lung cancer cells, but the underlying mechanism is unclear. In this study, scutellarin was used to treat A549 cells for 12, 24, and 48 h, followed by the addition of Tempo, a selective scavenger of mitochondrial reactive oxygen species (ROS) and SB431542, a transforming growth factor (TGF)-β1 receptor inhibitor. A dihydroethidium fluorescence probe was used to measure the intracellular ROS level, Cell Counting Kit-8 (CCK-8) was used to detect cell viability, and flow cytometry was performed to examine apoptosis. Western blots were used to detect the total protein level of TGF-β1, p-smad2, and cleaved caspase-3 in A549 cells. The results showed that scutellarin significantly inhibited cell viability and increased apoptosis. Scutellarin also promoted intracellular ROS production, TGF-β1/smad2 signaling pathway activation, and cleaved caspase-3 expression, which was partly reversed by Tempo. Moreover, scutellarin-induced intracellular ROS production and cleaved caspase-3 expression were inhibited by blocking the TGF-β1/smad2 pathway with SB431542. In conclusion, scutellarin promoted apoptosis and intracellular ROS accumulation, which could be abrogated by Tempo and SB431542 treatment in A549 cells. Our study indicated that scutellarin induced A549 cell apoptosis via the TGF-β1/smad2/ROS/caspase-3 pathway.

The main cause of steroid-induced necrosis of femoral head (SNFH) is excessive glucocorticoid (GC) intake. The aim of this article was to investigate the role of lncRNA NEAT1 as a molecular sponge to adsorb miR-23b-3p and regulate CYP1A2 in SNFH. Fluorescence in situ hybridization was used to localize lncRNA NEAT1. Human bone marrow mesenchymal stem cells (hBMSCs) were collected from patients with SNFH. The expression of lncRNA NEAT1, miR-23b-3p and CYP1A2 in hBMSCs were intervened. Compared to the control group, the lncRNA NEAT1 and CYP1A2 expression in the SNFH group was increased, while miR-23b-3p expression was decreased. GCs could inhibit the osteogenic differentiation of hBMSCs and upregulate the expression of lncRNA NEAT1. Knockdown of lncRNA NEAT1 could promote the proliferation and osteogenic differentiation of hBMSCs in the SNFH group. Overexpression of miR-23b-3p could partially counteract the effect of lncRNA NEAT1 on hBMSCs. CYP1A2 was confirmed to be a target of miR-23b-3p. Overexpression of CYP1A2 could partially rescue the effect of miR-23b-3p overexpression on hBMSCs. In conclusion, lncRNA NEAT1 as a ceRNA can adsorb miR-23b-3p and promote the expression of CYP1A2, which then inhibits the osteogenic differentiation of hBMSCs and promotes the progress of SNFH.

In various cancers, microRNAs (miRNAs) are abnormally expressed, including thyroid cancer (TC). In recent years, the incidence of TC has increased annually around the world. Compared with female patients, male TC patients are more likely to have a postoperative recurrence and lymph node metastasis, and hence need second treatments. However, the molecular biological processes underlying this phenomenon are not understood. Therefore, we collected data on miRNA expression and clinical information of male TC patients from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs were identified between male TC tissues and matched normal tissues. The Kaplan–Meier method, univariate and multivariate Cox regressions, and receiver operating characteristic curve analyses were performed to assess the association between miRNAs and the disease-free survival of male TC patients. Gene Ontology (GO) and the Kyoto Encyclopaedia of Gene and Genome (KEGG) enrichment analyses were then used to explore the function of miRNA target genes. Furthermore, we evaluated the ability of the miRNA biomarker to predict survival in female TC patients. As a result, a total of 118 differentially expressed miRNAs were identified, including 25 upregulated and 93 downregulated miRNAs. Among them, miR-451a and miR-16-1-3p were confirmed to be independent prognostic factors for the disease-free survival rate. The target genes of miR-451a and miR-16-1-3p were identified, and functional analysis showed that these genes were enriched in 25 Go and KEGG accessions, including cell signal transduction, motor adhesion, phagocytosis, regulation of transcription, cell proliferation, angiogenesis, etc. Neither miR-451a and miR-16-1-3p, nor a prediction model based on both miRNAs effectively predicted survival in female TC patients. In conclusion, both miR-451a and miR-16-1-3p may play important roles in the processes of male TC. The two-miRNA signature involving miR-1258 and miR-193a may serve as a novel prognostic biomarker for male TC patients.

Microglia are the principal glial cells involved in the processes of immune inflammation within both retina and optic nerve, especially under the context of glaucomatous neuropathy. Considering the distinguishing role of retinal microglia in glaucoma and the lack of established protocol for microglia isolation from animal glaucoma model, the present study aimed to develop and validate a method with characteristics of both simplicity and efficiency for retinal microglia isolation from chronic ocular hypertensive (COH) rats. A Percoll gradient of various concentrations was used to separate microglia from whole retinal cells of the COH rats and control group. The finally isolated microglia were identified by CD11b and Iba-1 immunofluorescence staining, and the cell viability was determined by trypan blue staining. Additionally, the proportion of microglia in the whole retina cells was identified by flow cytometry. Results showed that the survival rates of isolated retinal microglia with the Percoll gradient method were 67.2 ± 4% and 67.6 ± 3% in control and COH groups, respectively. The proportion of the microglia population in the whole retinal cells was about 0.4–0.93%. To conclude, the present study confirmed that the application of Percoll gradient could effectively separate microglia from retinas of COH rats, which will probably enrich the tool kit for basic researchers of glaucoma specialty and help with scientific investigations. Graphical abstract The application of Percoll gradient method could effectively separate microglia cells from retinas of COH rats.

In this pilot study, we compared the dynamic changes of circulating immune cells between patients with hepatocellular carcinoma (HCC) who underwent radiofrequency ablation (RFA) and hepatectomy. Seventy-three patients were enrolled in this study. Flow cytometry assay was performed to determine the immune cells in the peripheral blood mononuclear cells (PBMCs) before treatment and on days 7, 14, and 28 after treatment. We found that in the RFA group, the circulating cluster of differentiation (CD)4+ cells, the CD4+/CD8+ ratio, and natural killer (NK) cells continued to increase, and the circulating CD8+ cells continued to decrease after the treatment. In contrast, in the surgery group, the circulating CD4+ cells and CD4+/CD8+ ratio decreased over the first seven postoperative days and then began to increase, and CD8+ cells decreased on the first 7 postoperative days and began to increase thereafter. The changes of immune cells in tumor tissues consisted of an increase in the number of CD4+ cells, CD8+ cells, CD3+ cells, and NK cells immediately after RFA. Our results show that postoperative immune function continued to improve after RFA, but after surgery, it decreased in the first week and started to improve thereafter. These findings are important for clinicians when selecting the appropriate therapy for HCC.

It has been shown that the activation of calcineurin is involved in regulating ion channel remodeling in hypertrophic cardiomyocytes. But the precise role of calcineurin in the regulation of transient outward potassium current ( I to ), an ion channel associated with fatal arrhythmia, remains controversial. This study aimed to examine the effects of calcineurin Aβ ( CnAβ ) gene knockdown on I to channel remodeling and action potential duration (APD) in the hypertrophic ventricular myocytes of neonatal rats. Results showed that phenylephrine stimulation caused hypertrophy of ventricular myocytes, upregulation of CnAβ protein expression, downregulation of Kv4.2 mRNA and protein expression, a decrease in I to current density, and prolongation of APD. CnAβ gene knockdown significantly inhibited the effects of phenylephrine stimulation. Our data indicate that CnAβ gene knockdown can inhibit I to channel remodeling and APD prolongation in hypertrophic neonatal rat ventricular myocytes. This finding suggests that calcineurin may be a potential target for the prevention of malignant ventricular arrhythmia in a hypertrophic heart.

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.

Wnt/β‐catenin signaling is an evolutionarily conserved pathway and plays a crucial role in regulating cancer cell proliferation and tumorigenesis. However, the molecular mechanism behind the Wnt/β‐catenin signaling-mediated carcinogenesis and apoptosis resistance in oral squamous cell carcinoma is not well characterized so far. In the present study, we have investigated the effect of β‐catenin depletion of the perversely activated Wnt/β-catenin signaling pathway on apoptosis resistance and tumorigenesis of the human OSCC cell line SCC-55. RT-PCR and western blot analysis demonstrated that the Wnt/β-catenin signaling pathway and its downstream targets such as DKK1 and AXIN2 are aberrantly activated in SCC-55 cells. Furthermore, upon silencing (RNA interference) of β‐catenin in SCC-55, cells became more sensitive toward the chemotherapeutic drugs and thus resulted in apoptotic cell death. Meanwhile, flow cytometry analysis confirmed the enhanced apoptosis and activation of caspases in β‐catenin RNAi cells. Besides ensuing β-catenin–siRNA transfection, the cell proliferation and cancer colony generating efficiencies are significantly impeded compared to the non-transfected cells. Furthermore, the tumorigenicity was inhibited by the downregulation of OCT-4 in β‐catenin-silenced SCC-55 cells. Altogether, Wnt/β‐catenin signaling could potentially target anti-cancer drugs to induce apoptosis and achieve a better clinical outcome.

Oxidized low-density lipoprotein (ox-LDL) is a significant risk factor for various brain vascular diseases. Circular RNA (circRNA) is involved in the pathogenesis of brain vascular diseases. This study revealed the roles of circ_CHFR in ox-LDL-mediated cell proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT). Our results showed that circ_CHFR and EGFR expressions were dramatically upregulated, while miR-15a-5p expression was downregulated in ox-LDL-induced human brain microvessel endothelial cells (HBMECs) relative to control groups. circ_CHFR knockdown hindered the effects of ox-LDL exposure on cell proliferation, cell cycle, apoptosis, and EndoMT in HBMECs, whereas these impacts were abolished by miR-15a-5p inhibitor. In addition, circ_CHFR functioned as a sponge of miR-15a-5p and miR-15a-5p bound to EGFR. Thus, we concluded that circ_CHFR silencing hindered ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through sponging miR-15a-5p in HBMECs. Our findings provide a new mechanism for studying circRNA-directed therapy in ox-LDL-induced human brain vascular diseases.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs’ maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI.

Ubiquitin-conjugating enzyme E2T (UBE2T) functions as an E2 ubiquitin-conjugating enzyme in the ubiquitin-proteasome degradation system and mediates cellular processes, such as cell cycle, proliferation, and differentiation. UBE2T has been considered to be an oncogene in a variety of tumors. However, the oncogenic role of UBE2T in cervical cancer remains unclear. In this study, our results first showed that the expression of UBE2T was higher in both of cervical cancer tissues and cells than that in the normal tissues and cells. Knockdown of UBE2T reduced cervical cancer cell viability and suppressed the proliferation, invasion, and migration. However, overexpression of UBE2T contributed to cervical cancer cell growth and metastasis. Moreover, UBE2T overexpression cervical cancer cells demonstrated enhanced self-renewal capacity with upregulation of SOX2, Oct-4, and Nanog protein. Silencing of UBE2T downregulated protein expression of SOX2, Oct-4, and Nanog in cervical cancer cells reduced self-renewal capacity. Furthermore, ectopic UBE2T expression promoted protein expression of glucose-regulated protein 78 (GRP78) and focal adhesion kinase (FAK) phosphorylation in cervical cancer cells. The knockdown of UBE2T reduced protein expression of GRP78 and FAK phosphorylation. Collectively, UBE2T promoted cervical cancer stem cell traits and exerted an oncogenic role through activation of the GRP78/FAK pathway.

Several factors contribute to the development of breast cancer, including the immune system. This study is aimed to characterize the carriage of human leukocyte antigen (HLA)-DRB1*11 and 1*12 alleles in patients with breast cancer. This case-control study consisted of 96 histologically diagnosed breast cancer cases and 102 controls (cases without breast abnormalities). A multiplex polymerase chain reaction (PCR) was used to characterize the carriage of HLA-DRB1*11 and 1*12 alleles. The HLA-DRB1*11 allele was present in 26.59% of cases and 22.55% of controls. The HLA-DRB1*12 allele was present in 56.63% of cases and 55.88% of controls. This study found no direct association between the carriage of the HLA-DRB1*11 and HLA-DRB1*12 alleles and the occurrence of breast cancer. In addition, the deletion of the HLA-DRB1*11 allele is associated (beneficial effect) with obesity/overweight (OR = 0.13; 95% CI [0.01–1.14]; and p = 0.03) which is a risk for breast cancer. No direct association was found between the carriage of HLA-DRB1*11 and 1*12 alleles and breast cancer risk. However, further investigation of other HLA alleles involved in the occurrence of breast cancer may provide more information.

This study was conducted to assess whether Lactobacillus -containing probiotics could protect intestinal mucosa in rats during traumatic hemorrhagic shock and to determine its underlying mechanisms. Healthy male Sprague–Dawley rats (300 ± 20 g) were randomly divided into four groups. During the study, reverse transcription polymerase chain reaction, western blotting, and hematoxylin and eosin methods were used. There was a significant increase in the expression of toll-like receptor 4 (TLR4) in the rats that experienced traumatic hemorrhagic shock, along with increased mRNA of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Pretreatment with Lactobacillus -containing probiotics reduced TLR4 expression, decreased phosphorylation (Ser536) and acetylation (Lys310) of p65, and decreased TNF-α and IL-6 mRNA. The probiotics combined acetate Ringer’s group showed a less severe pathological manifestation compared to the other experimental groups. Lactobacillus -containing probiotics inhibited nuclear factor-kappa B signaling via the downregulation of TLR4, resulting in inflammatory homeostasis, which might be the mechanism whereby Lactobacillus protects the intestinal mucosa from damage caused by the traumatic hemorrhagic shock.

Osteonecrosis of the femoral head (ONFH) induced by glucocorticoids (GCs) has been considered to be associated with the dysfunction of bone marrow mesenchymal stem cells (BMSCs). Studies have reported that GCs can regulate the normal differentiation of BMSCs. However, the exact mechanism of this regulation remains unclear. In this study, we used methylprednisolone (MPS) to induce BMSCs, and then found that the Hippo signaling pathway was upregulated in a dose-dependent manner compared to that in the control group. In addition, the osteogenic ability of BMSCs was decreased, as evaluated by Alizarin Red S staining analysis and alkaline phosphatase activity assays, accompanied by the downregulated expression of Runx2, osteopontin, and osteocalcin. Additionally, the adipogenic capacity of BMSCs under the MPS conditions was increased, as identified by Oil Red O staining with upregulated triglyceride and PPARγ expression. Moreover, suppression by knockdown of MST1 was found to attenuate the Hippo signaling pathway and adipogenic differentiation, while enhancing osteogenic differentiation. In conclusion, our findings revealed that the Hippo signaling pathway was involved in GC-ONFH by affecting the osteogenic and adipogenic differentiation capacities of BMSCs. Our study could provide a basis for further investigation of the specific function of the Hippo pathway in ONFH.

Vascular hyporesponsiveness in the shock decompensation period is an important factor leading to death. Myosin light chain 20 (MLC 20 ) is the main effector protein that regulates vascular reactivity. However, whether the change in semicarbazide-sensitive amine oxidase (SSAO) expression during hypoxia can change the MLC 20 phosphorylation level, and its underlying mechanism were not clear. The amine oxidase copper containing 3 (AOC3) overexpressing adenovirus vector was constructed and transfected into rat intestinal microvascular endothelial cells (RIMECs) to overexpress SSAO, and the RIMECs were co-cultured with rat intestinal microvascular smooth muscle cells (RIMSCs). The changes in SSAO/inducible nitric oxide synthase (iNOS)/Rho associate coiled-coil containing protein kinase 1 (ROCK1) expression levels and MLC 20 phosphorylation level were detected. Here we found that the increased SSAO by AOC3 overexpression can decrease the iNOS expression level and its activity after hypoxia. In addition, RIMSCs co-cultured with RIMECs overexpressed with AOC3 gene had significantly higher ROCK1 protein level and MLC 20 phosphorylation level than RIMSCs co-cultured with normal RIMECs. Our study demonstrated that SSAO overexpression can significantly inhibit iNOS activity, promote RhoA/ROCK pathway activation, and increase the phosphorylation level of MLC 20 , which might be the potential mechanism in relieving the vascular hyporesponsiveness during shock decompensation.

Storkhead box 1 (STOX1) is a winged helix transcription factor structurally and functionally related to the forkhead family of transcription factors. Recent studies have highlighted its role in the central nervous system and revealed hints in the development of glioma. However, the expression profiles of STOX1 , its association with clinicopathological characteristics, and potential functions in glioma remain unknown. In this study, we analyzed three publicly available datasets including CGGA, TCGA, and Rembrandt and revealed a grade-dependent reduction in STOX1 expression in glioma ( P < 0.001). Chi-square test demonstrated that low STOX1 expression was significantly associated with older age at initial diagnosis ( P < 0.001), less IDH1 mutation ( P < 0.001), and advanced WHO grade ( P < 0.001). Moreover, multivariate Cox regression analysis showed that STOX1 expression may serve as a novel independent prognostic biomarker in glioma patients. Bioinformatic functional analysis (GSEA) predicted that STOX1 was related to many key cancer pathways including P53 signaling pathway ( P < 0.01), DNA replication ( P < 0.05), homologous recombination ( P < 0.05), and Wnt signaling pathway ( P < 0.05). Taken together, these findings suggested that STOX1 may be used as a novel predictive molecular biomarker for glioma grading and overall patient survival. Further investigations on the functional roles and therapeutic value of STOX1 in glioma are warranted.

Glioma is a type of common intracranial tumor. In this study, we investigated the molecular mechanism by which miR-378a-3p regulates cisplatin (CDDP) chemosensitivity in glioma cells via insulin-like growth factor 1 receptor (IGF1R). U251/CDDP cells were treated with CDDP and transfected with miR-378a-3p mimics, NC mimics, or pcDNA-IGF1R. qRT-PCR was used to measure the differential level of miR-378a-3p. CCK-8 assay was used to test cell proliferation, and flow cytometry was used to analyze apoptosis. The targeting relationship between miR-378a-3p and IGF1R was tested through a dual-luciferase reporter gene assay. In contrast to normal glial cells, the miR-378a-3p level decreased in human glioma U251 cells and had lower expression in U251/CDDP cells. Compared with the CDDP group, miR-378a-3p significantly caused the inhibition of U251/CDDP cell proliferation and enhanced apoptosis in the miR-378a-3p mimics + CDDP group. Another experiment confirmed that IGF1R was a target gene of miR-378a-3p, and overexpression of miR-378a-3p inhibited IGF1R expression. In addition, co-overexpression of miR-378a-3p and IGF1R induced the upregulation of the U251/CDDP cell proliferation and the inhibition of apoptosis in the miR-378a-3p mimics + pcDNA-IGF1R + CDDP group. This study confirmed that miR-378a-3p promoted the sensitivity of glioma cells to CDDP in glioma patients via targeting IGF1R to increase the therapeutic effect during chemotherapy.

The areca nut is one of the most commonly consumed psychoactive substances worldwide, with an estimated consumption by approximately 10% of the world’s population, especially in some regions of South Asia, East Africa, and the tropical Pacific. Arecoline, the major areca nut alkaloid, has been classified as carcinogenic to humans as it adversely affects various organs, including the brain, heart, lungs, gastrointestinal tract, and reproductive organs. Earlier studies have established a link between areca nut chewing and cardiac arrhythmias, and yet research pertaining to the mechanisms underlying cardiotoxicity caused by arecoline is still preliminary. The main purpose of this study is to test the hypothesis that arecoline causes cardiac fibrosis through transforming growth factor-β (TGF-β)/Smad-mediated signaling pathways. Male Wistar rats were injected intraperitoneally with low (5 mg/kg/day) or high (50 mg/kg/day) doses of arecoline for 3 weeks. Results from Masson’s trichrome staining indicated that arecoline could induce cardiac fibrosis through collagen accumulation. Western blot analysis showed that TGF-β and p-Smad2/3 protein expression levels were markedly higher in the arecoline-injected rat hearts than in those of the control rats. Moreover, arecoline upregulated other fibrotic-related proteins, including SP1-mediated connective tissue growth factor expression. Tissue-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, and matrix metalloproteinase (MMP) 9 were upregulated, and the inhibitor of MMP9 was downregulated. This study provides novel insight into the molecular mechanisms underlying arecoline-induced cardiac fibrosis. Taken together, the areca nut is a harmful substance, and the detrimental effects of arecoline on the heart are similar to that caused by oral submucous fibrosis.

Transforming growth factor (TGF)-β1 and mesenchymal stromal cells (MSCs) are two effective immunosuppressive agents for organ transplantation technology. This study aims to explore the molecular mechanism of TGF-β1-overexpressed MSCs on T cell immunosuppression. To achieve that, BM-MSCs were isolated from canine bone marrow, and their osteogenic differentiation and surface markers were detected. The TGF-β1 gene was transferred into lentivirus and modified MSCs (TGF-β1/MSCs) by lentivirus transfection. Furthermore, TGF-β1/MSCs were co-cultured with T cells to investigate their effect on differentiation and immune regulation. Results showed that TGF-β1/MSCs significantly downregulated the proportion of CD4 + CD8 + T cells in lymphocytes and significantly upregulated the proportion of CD4 + CD25 + T cells. Moreover, TGF-β1/MSCs significantly upregulated the expression of IL-10 in CD4 + T cells and downregulated the expression of IL-17A, IL-21, and IL-22. Meanwhile, interferon-γ (IFN-γ) neutralizing antibody blocked the effects of TGF-β1/MSCs on the differentiation inhibition of Th17. Overall, our results confirm the strong immunosuppressive effect of TGF-β1/MSCs in vitro and demonstrate that IFN-γ mediates the immunosuppressive effect of TGF-β1/MSC.

MTHFR is a crucial enzyme in folate metabolism. This study aimed to determine the relationship between MTHFR genetic polymorphism and elimination and toxicities of methotrexate (MTX). To do that, the study enrolled 145 patients diagnosed with acute lymphoblastic leukemia, who received chemotherapy following the Chinese Children’s Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL)-2015 protocol (clinical trial number: ChiCTR-IPR-14005706). We analyzed the effects of MTHFR C677T and A1298C polymorphisms on MTX elimination and toxicities. Patients with the MTHFR C677T TT genotype could tolerate a significantly higher MTX dose than those with the CC/CT genotype. However, patients with C677T TT genotypes had an increased risk of hypokalemia (1.369 to CC and 1.409 to CT types). The MTX infusion rate in patients with the MTHFR A1298C AC genotype was slightly lower than that in those with CC or AA genotypes. Patients with the A1298C AA genotype had a 1.405-fold higher risk of hepatotoxicity than those with the AC genotype ( P > 0.05). There was no significant difference between the prevalence of other toxicities among MTHFR C677T or A1298C genotypes ( P > 0.05). Neither MTHFR C677T nor A1298C polymorphisms were significantly associated with delayed MTX clearance. To conclude, MTHFR polymorphisms were not good predictors of MTX-related toxicities.

The aim of this study was to compare the diagnostic values of red blood cell distribution width-coefficient of variation (RDW-CV) and red blood cell distribution width-standard deviation (RDW-SD) in mid-pregnancy women with iron deficiency anemia (IDA). To obtain the results, 115 mid-pregnancy women with IDA, defined as the IDA group, and 142 healthy mid-pregnancy women, selected as the control group, were enrolled in this study. Hematological parameters and ferritin concentrations in the serum were analyzed. The efficiency of RDW-CV and RDW-SD to distinguish IDA from mid-pregnancy women was evaluated using receiver operating characteristic (ROC) curves. The RDW-SD value in the IDA group was significantly higher than that in the control group ( p < 0.05), while the RDW-CV value did not differ between them ( p = 0.84). Significantly negative correlations were found between RDW-CV ( r = −0.297, p = 0.001), RDW-SD ( r = −0.404, p = 0.000), and serum ferritin in the IDA group but not in the control group. For the diagnosis of IDA, RDW-CV and RDW-SD produced areas under the ROC curves of 0.58 and 0.84. To conclude, our results suggest that RDW-SD, but not RDW-CV, can be used as a diagnostic index of IDA for mid-pregnancy women.

Rare small cell neuroendocrine carcinoma (SCNEC) cases showed alpha fetoprotein (AFP) expression in the endometrium. In this study, we reported a case of uterine SCNEC expressing AFP. In addition, a literature review was performed to investigate the potential mechanism and the clinicopathological features of SCNEC to provide clinical guidance. A 65-year-old female was referred to our hospital due to vaginal bleeding for 1 month in November 2020. The clinical features were summarized. After total hysterectomy and removal of bilateral appendages, the histological examination and immunohistochemistry examination were performed. Histological findings showed that the cancer cells were arranged in a nest-like pattern distributed in a lamellar manner. The smooth muscles of the uterus were invaded by cancer cells. Cancer cells were relatively consistent in size. Small glandular duct-like and rosettes-like structures were distinguished, together with necrotic tissues. The deep staining showed that the amount of cytoplasm was lower in the nucleus. Partial cancer cells had small nucleolus with an irregular profile. There were some mitotic figures. Immunohistochemistry examination indicated that there was a diffuse expression of CK, Syn, CgA, CD56, CK8/18, P16, AFP, HepPar-1, Glypican-3, and Ki67 (90%). In this case, we reported a SCNEC patient expressing AFP, Glypican-3, and HepPar-1.

This long-term research was designed to evaluate whether superoxide dismutase (SOD) isoenzymes participate in the development of human gastrointestinal neoplasms and the potential influence of the sigma1 receptor (Sig1R) on the regulation of SOD gene expression during the neoplastic process. The experiments included human tissues from selected gastrointestinal tract tumors (liver cancer, colorectal adenocarcinoma, and colorectal cancer liver metastases). Activity, protein levels, and mRNA levels were determined for SOD isoenzymes and Sig1R. Additionally, markers of oxidative stress (glutathione, lipid peroxidation) were measured. The results showed significant changes in the antioxidant system activity in all examined types of tumors. SOD changed both in healthy cells and in neoplastic cells. The activity and expression of all studied enzymes significantly changed due to the advancement of tumor development. The Sig1R might be an additional regulator of the antioxidant system on which activity might depend on the survival and proliferation of cancer cells. Overall, the study shows that SOD1 and SOD2 are involved not only in the formation of neoplastic changes in the human gastrointestinal tissues (healthy intestine – colon tumor; healthy liver – liver cirrhosis – liver cancer) but also in the development of tumors in the sequence: benign tumor – malignant tumor – metastasis.

Taeniids, consisting of two genera Echinococcus and Taenia , are obligatory tapeworms of mammals, and their pathogenicity was due to infection with larval stages. Hydatid (the larval stage of Echinococcus granulosus ) and coenurus (the larval stage of Taenia multiceps ) cysts are prevalent in domestic, wild ruminants, livestock, swine, and dogs, and accidentally they could also be found in humans. They lead to different clinical manifestations that cause economic loss in livestock and human morbidity. In Saudi Arabia, few studies were performed on hydatid and coenurus cyst genetic variations. The main goal of the present study was to identify E. granulosus and T. multiceps cyst isolates collected from slaughtered Harri sheep in Saudi Arabia by partial sequencing with PCR amplification of the cytochrome C oxidase 1 ( COX 1) gene. Molecular and phylogenetic evaluation based on COX 1 sequences indicated that cyst isolates belong to E. granulosus and T. multiceps , respectively, successfully submitted in NCBI Genbank. Molecular characterization showed a low nucleotide diversity with two submitted isolates of coenurus with related isolates of Genbank. Conversely, E. granulosus isolates showed higher nucleotide diversity. The reported data could serve as a foundation for future molecular epidemiological and biological studies.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal-dominant genetic disorder, and mutations in the forkhead box L2 ( FOXL2 ) gene are one of the major genetic causes. As this study shows, there are many patients with BPES who do not have FOXL2 mutations, as the screening results in all family members were negative. Using whole-exome sequence analysis, we discovered another possible mutational cause of BPES in integrin subunit beta 5 ( ITGB5 ). The ITGB5 mutation (c.608T>C, p.Ile203Thr) appears in the base sequence of all BPES + patients in this family, and it appears to be a three-generation-inherited mutation. It can cause changes in base sequence and protein function, and there may be cosegregation of disease phenotypes. ITGB5 is located on the long arm of chromosome three (3q21.2) and is close to the known pathogenic gene FOXL2 (3q23). This study is the first to report ITGB5 mutations in BPES, and we speculate that it may be directly involved in the pathogenesis of BPES or indirectly through the regulation of FOXL2 .

We performed polyacrylamide gel electrophoresis of human proteins with sodium dodecyl sulfate, isolated proteins at multiple positions, and then used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to determine the protein identities. Although beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are 41.7 and 36 kDa proteins, respectively, LC-MS/MS identified their peptides at all the positions studied. The National Center for Biotechnology Information (USA) database lists only one ACTB mRNA but five GAPDH mRNAs and one noncoding RNA. The five GAPDH mRNAs encode three protein isoforms, while our bioinformatics analysis identified a 17.6 kDa isoform encoded by the noncoding RNA. All LC-MS/MS-identified GAPDH peptides at all positions studied are unique, but some of the identified ACTB peptides are shared by ACTC1, ACTBL2, POTEF, POTEE, POTEI, and POTEJ. ACTC1 and ACTBL2 belong to the ACT family with significant similarities to ACTB in protein sequence, whereas the four POTEs are ACTB-containing chimeric genes with the C-terminus of their proteins highly similar to the ACTB. These data lead us to conclude that GAPDH and ACTB are poor reference genes for determining the protein loading in such techniques as Western blotting, a leading role these two genes have been playing for decades in biomedical research.

Multiple methodologies have been reported to facilitate skin-derived precursor (SKP) growth, but the impact of plating density on SKP growth has not been studied. To determine the optimal plating density, we used six plating densities and two types of flasks for mouse SKP (mSKP) culture. On the 14th day, the number, diameter, and viability of mSKP spheres were compared by morphological assessment and cell counting kit 8, and we found the optimal plating density was 2.5 × 10 5 –5 × 10 5  cells/mL. In addition, we investigated the correlation between the SKP spheres and the adherent cell colonies in the serum-free culture system. We treated the adherent cell colonies with two culture conditions and characterized the cells generated from two conditions by immunocytochemistry and induced differentiation, respectively. The results elucidated that the adherent cell colonies differentiated into either mSKPs or dermal mesenchymal stem cells under appropriate culture conditions. In conclusion, mSKP spheres differentiated from the adherent cell colonies. The optimal plating density significantly promoted and advanced the proliferation of adherent cell colonies, which optimized mSKP growth and yield. The adherent cell colonies possessed the capacity of differentiating into different types of cells under appropriate culture conditions.

3,4-Dihydroxyphenylethanol (DOPET) is a polyphenol found in olive oil. The present study evaluated the protective role of DOPET on LPS provoked septic cardiac injury in a murine model. Four groups were used in the study ( n = 3): control, LPS, DOPET alone, and DOPET + LPS. LPS (15 mg/kg; i.p.); they were used to induce cardiac sepsis. The cardiac markers like LDH, CK-MB, and troponin-T, as well as inflammatory cytokines like TNF-α and IL-6 were measured in the serum. The antioxidants and oxidative stress parameters were measured in cardiac tissues. RT-PCR and western blot methods were done to evaluate the expression of inflammatory mediators and apoptotic markers. DOPET significantly decreased the cardiac markers (LDH, CK-MB, and troponin-T) and TNF-α and IL-6 level in the serum. DOPET effectively reduced the levels of MDA and NO in LPS intoxicated rats. DOPET also increased the levels of antioxidants like SOD, CAT, GPx, and GSH in LPS intoxicated rats. The mRNA levels of TNF-α, IL-6, and NF-κB were significantly downregulated by DOPET in cardiac tissues of LPS rats. The protein expression of Bcl-2 was upregulated, and Bax and caspase-3 were downregulated by DOPET. DOPET effectively attenuates LPS-induced cardiac dysfunction through its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Paired-like homeodomain 2 (PITX2) functions as a transcription factor to participate in vertebrate embryogenesis, and dysregulated PITX2 expression was associated with the progression of various cancers. The functional role of PITX2 in tumorigenesis of liver cancer remains unknown. Western blot analysis showed that expression levels of PITX2 were enhanced in the liver cancer tissues and cells. siRNAs targeting PITX2 induced downregulation of PITX2 in liver cancer cells. siRNA-induced knockdown of PITX2 decreased liver cancer cell viability and proliferation, while promoting cell apoptosis by increasing cleaved-PARP, cleaved caspase 3, and cleaved caspase 9. The knockdown of PITX2 repressed liver cancer cell migration and invasion. In conclusion, elevated PITX2 expression was associated with liver cancer progression through repression of cell apoptosis and promoting cell proliferation and metastasis, and silencing of PITX2 might serve as a potential therapeutic strategy for the treatment of liver cancer.

Endometrial cancer (EC) is one of the most common malignant tumors in the female reproductive system, which has been threatening the life and health of many women. Its incidence and mortality rate remain high, resulting in a low survival rate. In this study, the expression of cyclin-dependent kinase 9 (CDK9) in EC tissues was investigated, and its effect on the proliferation of EC cell line HEC-1B was preliminarily analyzed. RT-qPCR and Western blotting showed that CDK9 mRNA and protein were significantly reduced in the small interfering (si)RNA interference group compared with the siRNA control and blank control groups. MTT assay showed that the EC cell proliferative ability was significantly decreased, and phosphorylated-phosphatidylinositol 3 kinase (p-PI3K)/PI3K and phosphorylated-protein kinase B (p-AKT)/AKT were significantly reduced in the siRNA interference group compared with the siRNA control and blank control groups. In conclusion, the high expression of CDK9 is a factor of poor prognosis in EC, and the reduction of CDK9 can inhibit HEC-1B cell proliferation, which may be related to the inhibition on the activation of the PI3K/AKT signaling pathway.

The role of inflammation has been identified in the pathogenesis of diabetic ketoacidosis (DKA). The neutrophil/lymphocyte ratio (NLR) and white blood cells (WBC) can be used to predict a systemic inflammatory response. Changes in NLR and WBC levels have never been explored in type 1 diabetes mellitus (T1DM) patients with DKA and an uninfected state. This retrospective study included a total of 644 participants. NLR and WBC were measured in the control group ( n = 316) and in T1DM patients with mild-DKA ( n = 92), severe-DKA ( n = 52), and non-DKA ( n = 184) in an uninfected state. Then, we assessed the independent predictors of DKA occurrence in T1DM patients in an uninfected state. The diagnostic performance of variables was determined by receiver operating characteristic curve analysis. Serum NLR of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, NLR increases further and increases with the severity of DKA. In addition to diastolic blood pressure, blood urea nitrogen, glycated hemoglobin (HbA1c), and WBC, NLR was also independently associated with DKA in T1DM patients with an uninfected state (OR = 1.386, 95% CI: 1.127–1.705, p = 0.002). Furthermore, the diagnosis analysis showed that except for NLR and WBC, the area under the curve (AUC) of indicators with a statistical difference in patients with and without DKA were 0.747 for DKA diagnosis, and after the addition of NLR and WBC, the AUC was 0.806. The increased NLR level represents a low-cost and highly accessible predictor for DKA in T1DM patients with an uninfected state. The addition of inflammation indicators can play a statistically significant role in the prediction model of the DKA occurrence.

This study aimed to investigate the molecular mechanism under the pathophysiology of subarachnoid hemorrhage (SAH) and identify the potential biomarkers for predicting the risk of SAH. Differentially expressed mRNAs (DEGs), microRNAs, and lncRNAs were screened. Protein–protein interaction (PPI), drug–gene, and competing endogenous RNA (ceRNA) networks were constructed to determine candidate RNAs. The optimized RNAs signature was established using least absolute shrinkage and selection operator and recursive feature elimination algorithms. A total of 124 SAH-related DEGs were identified, and were enriched in inflammatory response, TNF signaling pathway, and others. PPI network revealed 118 hub genes such as TNF , MMP9 , and TLR4 . Drug–gene network revealed that chrysin targeted more genes, such as TNF and MMP9 . JMJD1C - AS - hsa - miR - 204 - HDAC4 / SIRT1 and LINC01144 - hsa - miR - 128 - ADRB2 / TGFBR3 regulatory axes were found from ceRNA network. From these networks, 125 candidate RNAs were obtained. Of which, an optimal 38 RNAs signatures (2 lncRNAs, 1 miRNA, and 35 genes) were identified to construct a Support Vector Machine classifier. The predictive value of 38 biomarkers had an AUC of 0.990. Similar predictive performance was found in external validation dataset (AUC of 0.845). Our findings provided the potential for 38 RNAs to serve as biomarkers for predicting the risk of SAH. However, their application values should be further validated in clinical.

Renal ischemia-reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI). So far, there have been many studies on renal IRI, although an effective treatment method has not been developed. In recent years, growing evidence has shown that small noncoding RNAs play an important regulatory role in renal IRI. This article aims to explore whether microRNA-25-3p (miR-25-3p) plays a role in the molecular mechanism of renal IRI. The results showed that the expression level of miR-25-3p was significantly downregulated in a rat renal IRI model, and this result was confirmed with in vitro experiments. After the hypoxia-reoxygenation treatment, the apoptosis level of NRK-52E cells transfected with miR-25-3p mimics decreased significantly, and this antiapoptotic effect was antagonized by miR-25-3p inhibitors. In addition, we confirmed that DKK3 is a target of miR-25-3p. miR-25-3p exerts its protective effect against apoptosis on NRK-52E cells by inhibiting the expression of DKK3, and downregulating the expression level of miR-25-3p could disrupt this protective effect. In addition, we reconfirmed the role of miR-25-3p in rats. Therefore, we confirmed that miR-25-3p may target DKK3 to reduce renal cell damage caused by hypoxia and that miR-25-3p may be a new potential treatment for renal IRI.

Nanotechnology is the fabrication, characterization, and potential application of various materials at the nanoscale. Over the past few decades, nanomaterials have attracted researchers from different fields because of their high surface-to-volume ratio and other unique and remarkable properties. Cobalt and cobalt oxide nanoparticles (NPs) have various biomedical applications because of their distinctive antioxidant, antimicrobial, antifungal, anticancer, larvicidal, antileishmanial, anticholinergic, wound healing, and antidiabetic properties. In addition to biomedical applications, cobalt and cobalt oxide NPs have been widely used in lithium-ion batteries, pigments and dyes, electronic thin film, capacitors, gas sensors, heterogeneous catalysis, and for environmental remediation purposes. Different chemical and physical approaches have been used to synthesize cobalt and cobalt oxide NPs; however, these methods could be associated with eco-toxicity, cost-effectiveness, high energy, and time consumption. Recently, an eco-friendly, safe, easy, and simple method has been developed by researchers, which uses biotic resources such as plant extract, microorganisms, algae, and other biomolecules such as starch and gelatin. Such biogenic cobalt and cobalt oxide NPs offer more advantages over other physicochemically synthesized methods. In this review, we have summarized the recent literature for the understanding of green synthesis of cobalt and cobalt oxide NPs, their characterization, and various biomedical applications. Graphical abstract

This study aims to investigate the effects of different selenium (Se) sources on the growth performance of Chinese broilers and provide a scientific rationale for adding Se additives to broiler feed. Relevant studies that meet standard inclusion criteria were identified and extracted from China National Knowledge Infrastructure and Wanfang and Chinese Scientific Journal (VIP) databases. A total of 9 studies with 539 subjects were included. A meta-analysis was performed with STATA15.0 to estimate the combined standardized mean difference (SMD) with a 95% confidence interval (95% CI). Heterogeneity test of articles was examined by Q-test, and the results showed that P values of feed conversion ratio, average daily gain (ADG), and average daily intake were all less than 0.05, suggesting a strong heterogeneity among the selected literature. Therefore, the random effect model is selected to calculate the SMD of the three indexes. The combined SMDs (95% CI) of feed:gain, ADG, and average daily feed intake (ADFI) were −0.39 (−1.03, 0.25), 0.26 (−0.29, 0.81), and −1.45 (−3.09, 0.20), respectively, and the P values were all less than 0.05. This study shows that the absolute differences in the growth performance (feed:gain, ADG, and ADFI) of broilers fed with either organic or inorganic Se supplements at the same dose were quite small. The P values of Egger’s test were 0.770, 0.089, and 0.426, respectively, for the above indexes, showing no significant publication bias. Sensitivity analysis ensured the stability and reliability of the results. In summary, the effects of organic and inorganic Se in feed on the growth performance of broilers are statistically equal.

Domestic and international crops and livestock trade remain fragile among Zimbabwean smallholder farmers. Commercial crop-livestock integration in climate change vulnerable areas is low and sparsely documented. Practice, knowledge, and attitude indicators influencing participation of smallholder farmers in crop-livestock integrated platforms as a hedge against climate change-induced risks and uncertainties were assessed. A survey with 240 farmers in Insiza district, Matabeleland province, Zimbabwe was conducted. A modified knowledge, attitude, and perception framework was used to analyze data from six wards supported by World Vision through supplementary livelihood programs on crop-livestock integration. Conventional crop-livestock (63%), mixed crops-livestock (25%), and traditional grains-livestock (12%) options were dominant. There was a thin presence of stakeholders with a limited number of local buyers, contracting companies, and agro-dealers who participate on these platforms. Farmers have the knowledge, positive attitude, and motivated perceptions about the potential of traditional grains-livestock mechanisms to reduce climate change welfare compromising factors. Unbalanced policies, limited financing, and uncompetitive marketing channels limit the uptake of this option. Traditional grains-livestock alternatives should be supported in semi-arid environments to reduce food, income, and nutrition insecurity. Public-private partnerships should establish value addition systems to increase the market size of traditional grains-livestock products and enhance commercialization.

Polygonatum odoratum (Mill.) Druce (POD) is a natural plant widely used for food and medicine, thanks to its rich content of a strong antioxidant agent called homoisoflavones. However, food processing methods could affect the stability of POD flavones, resulting in changes to their antioxidant activity. This study attempts to evaluate the antioxidant activity of POD flavones subject to different processing methods and determines which method could preserve the antioxidant activity of POD flavones. Therefore, flavones were extracted from POD samples, which had been treated separately with one of the four processing methods: extrusion, baking, high-pressure treatment, and yeast fermentation. After that, the antioxidant activity of the flavones was subject to in vivo tests in zebrafish embryos. The results show that yeast fermentation had the least disruption to the antioxidant activity of POD flavones, making it the most suitable food processing method for POD. By contrast, extrusion and high-pressure treatment both slightly weakened the antioxidant activity of the flavones and should be avoided in food processing. The research results provide a reference for the development and utilization of POD and the protection of its biological activity.

The purpose of this study was to assess the relationship between 25-hydroxyvitamin D (25(OH)D), urinary iodine concentration (UIC), and type 2 diabetes mellitus (T2DM) risk and complications and to establish a model to predict T2DM in the general population. A total of 567 adults (389 T2DM patients and 178 controls) were enrolled, and the levels of 25(OH)D, iodine, and blood biochemical parameters were measured. Pearson’s correlation analysis showed an inverse correlation between 25(OH)D level, UIC, and T2DM risk. Low 25(OH)D level was a risk factor for developing T2DM (OR, 0.81; 95% CI, 1.90–2.63; P = 0.043) after adjustment for multiple risk factors. 25(OH)D level and UIC were inversely correlated with short-term and long-term glucose levels. 25(OH)D deficiency was also associated with a high incidence of T2DM complicated with thyroid dysfunction. A prediction model based on 25(OH)D, iodine status, and other risk factors was established and recommended to screen high-risk T2DM in the general population and provide early screening and timely treatment for them.

“Bryndza” cheese is an important Slovak traditional regional product. New knowledge on the role of microorganisms involved the “Bryndza” ripening process may provide valuable data on its quality and safety. In our study, the “Bryndza” made from pasteurized ewes milk was studied towards total count of bacteria, coliforms bacteria, enterococci, lactic acid bacteria, and microscopic filamentous fungi. All those groups of microbiota were detected using classical microbiological methods and identified using mass spectrometry. A total of 3,758 isolates were identified with score higher than 2.00. Altogether, 13 families, 24 genus, and 44 species of microbiota were identified in Slovak cheese “Bryndza.” The most often isolated species were yeasts Yarrowia lipolitica and Dipodascus geotrichum and the lactic acid bacteria Lactobacillus paracasei subsp. paracasei .

This article attempts to determine the most accurate classification method for different abalone-flavoring liquids. Three common voltammetric detection methods, namely, linear sweep voltammetry (LSV), cyclic voltammetry (CV), and square-wave voltammetry (SWV), were considered. To compare their classification accuracies of abalone-flavoring liquids, three methods were separately adopted to classify five different abalone-flavoring liquids, using a four-electrode (Au, Pt, Pd, and W) sensor array. Then the data acquired by each method were subject to the principal component analysis (PCA): the first three principal components whose eigenvalues were greater than 1 were extracted from each set of data; the cumulative variance contribution rate and the principal component scores of each method were obtained. The PCA results show that the first three principal components obtained by the CV had the highest cumulative variance contribution rate (91.307%), indicating that the CV can more comprehensively characterize the information of abalone-flavoring liquid samples than the other two methods. According to the principal component scores, compared with those of LSV and SWV, the same kind of samples detected by the CV were highly clustered and the different kinds of samples detected by the CV were greatly dispersed. This indicates that the CV can effectively distinguish between the five abalone-flavoring liquids. Finally, the detection data were further verified through probabilistic neural network and a support vector machine algorithm optimized by genetic algorithm. The results further confirm that the CV is more accurate than the other two methods in the classification of abalone-flavoring liquids. Therefore, the CV was recommended for the classification of abalone-flavoring liquids.

The main purpose of this research was the identification and characterization of low-molecular-weight glutenin subunit (LMW-GS) composition in common wheat and the determination of the effect of these proteins on the rheological properties of dough. The use of capillary zone electrophoresis and reverse-phase high-performance liquid chromatography has made it possible to identify four alleles in the Glu-A3 and Glu-D3 loci and seven alleles in the Glu-B3 locus, encoding LMW-GSs in 70 varieties and breeding lines of wheat tested. To determine the technological quality of dough, analyses were performed at the microscale using a TA.XT Plus Texture Analyzer. Wheat varieties containing the Glu-3 loci scheme ( Glu-A3b , Glu-A3f at the Glu-A3 locus; Glu-B3a , Glu-B3b , Glu-B3d , Glu-B3h at the Glu-B3 locus; Glu-D3a , Glu-D3c at the Glu-D3 locus) determined the most beneficial quality parameters.

Mastitis is a cow disease usually signalized by irritation, swelling, and soreness of the udder. It is characterized by physical, chemical, and biological changes in the udder and milk. The aim of this study was to detect and characterize pathogens causing subclinical mastitis (SCM) from the milk of dairy cows of small-scale farmers through culture and molecular techniques. Milk was collected from 32 cows belonging to 8 small-scale farmers around Harrismith District, South Africa. The results showed that screening of SCM by California mastitis test and somatic cell counts (SCC) was 21.87 and 25%, respectively. Culture methods revealed the presence of Staphylococcus aureus at 93% followed by Streptococci spp. and Escherichia coli at 36.4 and 13.3%, respectively. The PCR could only detect E. coli , while single-molecule real-time sequencing showed a total of 2 phyla, 5 families, 7 genera, and 131 species. Clostridiaceae was the most abundant family, while Romboutsia was the most abundant genus followed by Turicibacter spp. The present study has documented the occurrence of SCM causing pathogens in milk collected from cows of small-scale farmers in Harrismith, indicating that SCM may be present at higher levels than expected.

Microplastics (MPs) have been documented in different foodstuffs and beverages, that could affect human health due to their ingestion. Furthermore, seafood contamination with MPs puts pillars of food availability and utilization at risk. The present study investigates MPs and toxic elements pollution in commercially canned fishes from Taif governorate markets. Seven different canned fishes’ brands were used in the present study from different manufacturer countries and purchased from Taif markets. Tissue samples were digested by 10% of KOH; then, dry filters were analyzed by Fourier-transform infrared spectroscopy to detect MPs. Filtrates were used to detect any potentially toxic elements by inductively coupled plasma. Different MPs were detected in edible tissue, such as canned Tuna contaminated with nylon, 1,2-polybutadiene, and ethylene vinyl alcohol. Sardines contain ethylene vinyl alcohol and poly(vinyl stearate), but Salmon does not have any MPs. Different elements were present in the selected samples in the decreasing order of Al > Se > Zn and traces of As and Sb. Canned fishes were contaminated with MPs and potentially toxic elements. This contamination could be a warning of the potential health risks with the long-term exposure. Therefore, it is recommended to include micro-, meso-, and even nanoplastics in the guidelines of testing food safety management systems.

Vitally essential red fluids like packed cells and red wine are seriously influenced in quality when stored over prolonged periods. In the case of red cell concentrates, the resulting storage lesion has particular significance in perioperative medicine. We hypothesized that, in contrast, aging rather improves the properties of red wine in several ways. A translational approach, including (I) in vitro experiments, (II) a randomized, blinded crossover trial of acute clinical effects, and (III) a standardized red wine blind tasting was used. Three monovarietal wines (Cabernet Sauvignon, Chianti, Shiraz) in three different vintages (range 2004–2016), each 5 years different, were assessed. Assessments were performed at a German university hospital (I, II) and on a garden terrace during a mild summer evening (III). Young wines induced cell stress and damage while significantly reducing cytoprotective proteins in HepG2 hepatoma cells. Sympathetic activity and multitasking skills were altered depending on wines’ ages. Hangovers tended to be aggravated by young red wine. Aged variants performed better in terms of aroma and overall quality but worse in optical appearance. We found no evidence for a red wine storage lesion . However, we plead for consensus-based guidelines for proper storage, as it is common in clinical medicine.

This study aims to explore the relationship between the iodine status and thyroid dysfunction (TD) in pregnant women and establish a model to guide them to prevent excessive iodine intake. A total of 515 pregnant women were enrolled in the study. Urinary iodine concentration (UIC), thyroid hormones, and thyroid autoantibodies were measured, and then a logistic regression model was established. The median UIC of pregnant women was 174 ± 120 μg/L. Multivariate logistic regression analysis indicated that multivitamin supplements containing iodine and frequent seafood consumption were risk factors for excessive iodine (UIC ≥500 μg/L). Besides, excessive iodine was a risk factor for TD. Iodine excess was associated with a high prevalence of TD in pregnant women, especially TPOAb-positive women ( P < 0.05). A logistic regression model based on potential risk factors was established to predict the risk of excessive iodine intake among pregnant women and provide guidance to minimize the risk of excessive iodine intake, thus reducing the risk of TD.

Dendrobium huoshanense has been used for centuries in China and its polysaccharides are the main active components in treating loss of body fluids resulting from fever and asthenic symptoms. However, the biosynthetic pathway of polysaccharides in D. huoshanense remains to be elucidated. In this study, we obtained a guanosine diphosphate (GDP)-mannose pyrophosphorylase (DhGMPP) from D. huoshanense and characterized its function to catalyze the conversion of α-D-mannose-phosphate to GDP-D-mannose involved in the production of polysaccharides. DhGMPP , with the open reading frame of 1,245 bp, was isolated from RNA-Seq data of D. huoshanense . Phylogenetic analysis as well as sequence characterization suggested its involvement in the biosynthesis of GDP-D-mannose. In vitro enzyme assay demonstrated that GMPP encoded a pyrophosphorylase that converted α -D-mannose-phosphate and GTP into GDP-D-mannose. Identification of DhGMPP could provide more insights into the mechanism concerning polysaccharide biosynthesis in D. huoshanense and be utilized for enhancing polysaccharide accumulation through metabolic engineering.

SQUAMOSA promoter-binding protein-like (SPL) transcription factors are very important for the plant growth and development. Here 15 RoSPLs were identified in Rubus occidentalis . The conserved domains and motifs, phylogenetic relationships, posttranscriptional regulation, and physiological function of the 92 SPL family genes in Fragaria vesca , Malus domestica , Prunus persica , R. occidentalis , and Pyrus pyrifolia were analyzed. Sequence alignment and phylogenetic analysis showed the SPL proteins had sequence conservation, some FvSPLs could be lost or developed, and there was a closer relationship between M. domestica and P. pyrifolia , F. vesca and R. occidentalis , respectively. Genes with similar motifs clustering together in the same group had their functional redundancy. Based on the function of SPLs in Arabidopsis thaliana , these SPLs could be involved in vegetative transition from juvenile to adult, morphological change in the reproductive phase, anthocyanin biosynthesis, and defense stress. Forty-eight SPLs had complementary sequences of miR156, of which nine PrpSPLs in P. persica and eight RoSPLs in R. occidentalis as the potential targets of miR156 were reported for the first time, suggesting the conservative regulatory effects of miR156 and indicating the roles of miR156-SPL modules in plant growth, development, and defense response. It provides a basic understanding of SPLs in Rosaceae plants.

Leaf rust caused by the fungus Puccinia recondita f. sp. tritici is one of the most dangerous diseases of common wheat. Infections caused by fungal pathogens reduce the quantity and quality of yields of many cereal species. The most effective method to limit plant infection is to use cultivars that show rust resistance. Genetically conditioned horizontal-type resistance (racial-nonspecific) is a desirable trait because it is characterized by more stable expression compared to major (R) genes that induce racially specific resistance, often overcome by pathogens. Horizontal resistance is conditioned by the presence of slow rust genes, which include genes Lr34 and Lr46 . This study aimed to identify markers linked to both genes in 64 common wheat lines and to develop multiplex PCR reaction conditions that were applied to identify both genes simultaneously. The degree of infestation of the analyzed lines was also assessed in field conditions during the growing season of 2017 and 2018. Simple sequence repeat anchored-polymerase chain reaction (SSR-PCR) marker csLV was identified during analysis in line PHR 4947. The presence of a specific sequence has also been confirmed in multiplex PCR analyses. In addition to gene Lr34 , gene Lr46 was identified in this genotype. Lines PHR 4947 and PHR 4819 were characterized by the highest leaf rust resistance in field conditions. During STS-PCR analyses, the marker wmc44 of gene Lr46 was identified in most of the analyzed lines. This marker was not present in the following genotypes: PHR 4670, PHR 4800, PHR 4859, PHR 4907, PHR 4922, PHR 4949, PHR 4957, PHR 4995, and PHR 4997. The presence of a specific sequence has also been confirmed in multiplex PCR analyses. Genotypes carrying the markers of the analyzed gene showed good resistance to leaf rust in field conditions in both 2017 and 2018. Research has demonstrated that marker assisted selection (MAS) and multiplex PCR techniques are excellent tools for selecting genotypes resistant to leaf rust.

Taxus species have attracted much attention for their potency in cancer treatment. However, investigating the bioactivities of Taxus species is a complex task, due to their diversity, slow growth, and endangered state. The most important Taxus species in China are Taxus chinensis ( T. chinensis ), Taxus cuspidata ( T. cuspidata ), and Taxus × media ( T. media ), which mainly grow in the northeastern region. This article probes deep into the differences among the leaves of T. chinensis , T. cuspidata , and T. media , with the aid of gas chromatography-mass spectrometry (GC-MS). Through GC-MS, 162 compounds were detected in the samples and found to contain 35 bioactive metabolites. On this basis, 20 metabolites with significant bioactivities (antibiotic, antioxidant, anticancer, and antiaging effects) were identified via unsupervised learning of principal component analysis and supervised learning of partial least squares-discriminant analysis. The results show that T. media has the most prominent antibiotic, antioxidant, and anticancer effects, while T. cuspidata has the most diverse and abundant metabolites that slow down aging.

Myricaria laxiflora (Tamaricaceae) is an endangered plant that is narrowly distributed in the riparian zone of the Three Gorges, along the Yangtze River, China. Using bright-field and epifluorescence microscopy, we investigated the anatomical and histochemical features that allow this species to tolerate both submerged and terrestrial environments. The adventitious roots of Myr. laxiflora had an endodermis with Casparian bands and suberin lamellae; the cortex and hypodermal walls had lignified thickenings in the primary structure. In the mature roots, the secondary structure had cork. The apoplastic barriers in stems consisted of a lignified fiber ring and a cuticle at the young stage and cork at the mature stage. The leaves had two layers of palisade tissue, a hyaline epidermis, sunken stomata, and a thick, papillose cuticle. Aerenchyma presented in the roots and shoots. Several Myr. laxiflora structures, including aerenchyma, apoplastic barriers in the roots and shoots, were adapted to riparian habitats. In addition, shoots had typical xerophyte features, including small leaves, bilayer palisade tissues, sunken stomata, a thick, papillose cuticle, and a hyaline epidermis. Thus, our study identified several anatomical features that may permit Myr. laxiflora to thrive in the riparian zone of the Three Gorges, China.

To understand the molecular mechanism of the resistance to potato wart disease, we used the potato cultivar Qingshu 9 as the experimental material and prepared potato samples with different levels of disease through inoculation. The RNAs of the samples were extracted, and transcriptome analysis was performed on the samples not infected by the disease (control group) and also on the samples with different levels of disease, with the aid of high-throughput sequencing. Next, the differentially expressed genes (DEGs) associated with the resistance to potato wart disease were identified based on the analysis results. Using bioinformatic tools, the DEGs were functionally annotated, classified, and enriched in related metabolic pathways. The main results are as follows: Compared with the control group, 4 DEGs were identified in the samples with light disease, 52 were found in the samples with medium disease, and 214 were discovered in the samples with heavy disease. Potato mainly resists the wart disease by suppressing its gene expression, and the degree of suppression depends on the level of the disease; the disease resistance might be dominated by cellular nucleic acid-binding protein, AP2-like transcription factor, and E3 ubiquitin-protein ligase. This research provides new insights into the molecular mechanism of potato resistance against wart disease.

Plant glycosyltransferase 2 (GT2) family genes are involved in plant abiotic stress tolerance. However, the roles of GT2 genes in the abiotic resistance in freshwater plants are largely unknown. We identified seven GT2 genes in duckweed, remarkably more than those in the genomes of Arabidopsis thaliana , Oryza sativa , Amborella trichopoda , Nymphaea tetragona , Persea americana , Zostera marina , and Ginkgo biloba , suggesting a significant expansion of this family in the duckweed genome. Phylogeny resolved the GT2 family into two major clades. Six duckweed genes formed an independent subclade in Clade I, and the other was clustered in Clade II. Gene structure and protein domain analysis showed that the lengths of the seven duckweed GT2 genes were varied, and the majority of GT2 genes harbored two conserved domains, PF04722.12 and PF00535.25. The expression of all Clade I duckweed GT2 genes was elevated at 0 h after salt treatment, suggesting a common role of these genes in rapid response to salt stress. The gene Sp01g00794 was highly expressed at 12 and 24 h after salt treatment, indicating its association with salt stress resilience. Overall, these results are essential for studies on the molecular mechanisms in stress response and resistance in aquatic plants.

Salt stress affects plant physiology, development, and growth. This research investigated varied salinity levels on growth traits and ions accumulation of four zoysiagrasses and aimed to identify phenotypic traits associated with variability in salinity tolerance. In this study, “S001” zoysiagrass ( Zoysia sinica ), “Diamond” zoysiagrass ( Zoysia matrella ), “J026” zoysiagrass ( Zoysia japonica ), and “M001” zoysiagrass ( Zoysia macrostachya ) were grown in plastic pots and exposed to 1/2 Hoagland nutrient solution amended with different amounts of NaCl for 120 days. At the end of the experiment, growth traits and ion contents were determined. The results showed that the salt-tolerance of four zoysiagrasses ranked as “M001” > “Diamond” > “J026” > “S001” according to percent green leaf canopy area (GLCA) after 120 days of salinity treatment. Although dry leaf weight, leaf length/width, and shoot height were significantly decreased by salinity treatments for all turfgrasses, the salt-tolerant species had a smaller drop. Besides, ions secretion capacity and Na + concentration in leaf and root increased, but K + concentration together with leaf and root K + /Na + ratios decreased with the increasing concentration of the salinity. However, the salt-tolerant species exhibited strong K + absorption and transportation ability and a high salt secretion capacity. The results indicated that growth traits and ions regulation were related to variability in tolerance of diverse zoysiagrasses to salt stress.

The sterile line is the basis of crop heterosis utilization. To broaden the sources of male sterility in tobacco, the Ntms1 (Nicotiana tabacum L. ms1) gene was cloned from the tobacco variety K326 by homologous cloning based on the Cams1 ( Capsicum annuum L. ms1 ) gene sequence of male-sterility genes in pepper. The protein structure and physicochemical properties of the two genes were determined by bioinformatics analysis, and the function of the Ntms1 gene was verified by the CRISPR/Cas9 system. The results showed that the sequences of Ntms1 and Cams1 were 85.25% similar, and plant homeodomains were found in both genes; the physical and chemical properties were also very similar. It is speculated that the Ntms1 gene had the same function as the Cams1 gene in controlling male sterility. Compared to the wild-type plants, the filaments of the Ntms1 knockout mutant plants were shorter, and the stamen was shorter than the pistil. The anthers did not develop fully and had few viable pollen grains; the tapetum and the anther wall had developed abnormally, and the anther chamber was severely squeezed. The malondialdehyde content in the mutant plants was significantly higher than that in the wild-type plants, while self-fertility was significantly lower in the mutant plants. The results showed that the Ntms1 gene plays an important role in regulating fertility in tobacco.

In recent years, the pathogen that causes leaf blast on Amomum tsao-ko repeatedly infected the plants in a large area of Luchun County, Honghe Prefecture, Yunnan Province, China. The disease is caused by the pathogen Pyricularia variabilis . The effects of light, temperature, pH, carbon, and nitrogen sources on the growth of the pathogen were determined, and its sensitivity to six fungicides was determined using the mycelial growth rate method. The optimal conditions for mycelial growth were as follows: temperature: 20–25°C; carbon source: maltose, nitrogen source beef extract, media corn flour, and potato dextrose agar. The mycelia could grow under four types of light conditions: 24 h light, 24 h dark, 12 h light/12 h dark, and 16 h light/8 h dark. In addition, Propiconazole was the most effective inhibitor, with an EC 50 value of 0.030 μg/mL, and prochloraz was the second most effective, with an EC 50 value of 0.076 μg/mL. It is suggested that the two fungicides should be alternated when used in production. Carbendazim and chlorothalonil were ineffective in inhibiting the fungus, with EC 50 values of 6.137 and 3.765 μg/mL, respectively.

Mevalonate pyrophosphate decarboxylase ( MPD ) is a key enzyme in terpenoid biosynthesis. MPD plays an important role in the upstream regulation of secondary plant metabolism. However, studies on the MPD gene are relatively very few despite its importance in plant metabolism. Currently, no systematic analysis has been conducted on the MPD gene in plants under the order Apiales, which comprises important medicinal plants such as Panax ginseng and Panax notoginseng. This study sought to explore the structural characteristics of the MPD gene and the effect of adaptive evolution on the gene by comparing and analyzing MPD gene sequences of different campanulids species. For that, phylogenetic and adaptive evolution analyses were carried out using sequences for 11 Campanulids species. MPD sequence characteristics of each species were then analyzed, and the collinearity analysis of the genes was performed. As a result, a total of 21 MPD proteins were identified in 11 Campanulids species through BLAST analysis. Phylogenetic analysis, physical and chemical properties prediction, gene family analysis, and gene structure prediction showed that the MPD gene has undergone purifying selection and exhibited highly conserved structure. Analysis of physicochemical properties further showed that the MPD protein was a hydrophilic protein without a transmembrane region. Moreover, collinearity analysis in Apiales showed that MPD gene on chromosome 2 of D. carota and chromosome 1 of C. sativum were collinear. The findings showed that MPD gene is highly conserved. This may be a common characteristic of all essential enzymes in the biosynthesis pathways of medicinal plants. Notably, MPD gene is significantly affected by environmental factors which subsequently modulate its expression. The current study’s findings provide a basis for follow-up studies on MPD gene and key enzymes in other medicinal plants.

Drought is among the most important natural disasters with severe effects on animals and plants. MicroRNAs are a class of noncoding RNAs that play a crucial role in plant growth, development, and response to stress factors, including drought. However, the microRNAs in drought responses in common vetch ( Vicia sativa ), an annual herbaceous leguminous plant commonly used for forage by including it in mixed seeding during winter and spring, have not been characterized. To explore the microRNAs’ response to drought in common vetch, we sequenced 10 small RNA (sRNA) libraries by the next-generation sequencing technology. We obtained 379 known miRNAs belonging to 38 families and 47 novel miRNAs. The two groups had varying numbers of differentially expressed miRNAs: 85 in the comparison group D5 vs C5 and 38 in the comparison group D3 vs C3. Combined analysis of mRNA and miRNA in the same samples under drought treatment identified 318 different target genes of 123 miRNAs. Functional annotation of the target genes revealed that the miRNAs regulate drought-responsive genes, such as leucine-rich repeat receptor-like kinase-encoding genes (LRR-RLKs), ABC transporter G family member 1 (ABCG1), and MAG2-interacting protein 2 (MIP2). The genes were involved in various pathways, including cell wall biosynthesis, reactive oxygen removal, and protein transport. The findings in this study provide new insights into the miRNA-mediated regulatory networks of drought stress response in common vetch.

The effects of ventilation and sucrose concentration on proliferation and organogenesis of pistachio cutting and photosynthetic performance of two in vitro cultures of pistachio rootstocks have been assessed. The apical leaf buds (Qazvini and UCB1 cultivars) were cultured in filter vessels containing Murashige and Skoog medium supplemented with 0, 10, 15, and 30 g L − 1 of sucrose. The plants treated with 10, 15, and 30 g L − 1 sucrose showed no significant differences regarding the measured traits; therefore, this treatment was set aside from the final statistical analyses. Use of different ventilation systems showed to be suitable for increasing the growth of pistachio. Referring to root production difficulties under in vitro cultivation of pistachio, ventilation increased the root production and length. However, the full ventilation system was more effective in improving the growth properties. Regression between fluorescence feature vs root length showed that F v / F m had a significant positive relationship with root length. Stomata of cell parameters under ventilation systems improved compared to no ventilation, which was highly similar to the trend in the greenhouse. The overall results indicated that low concentrations of sucrose (e.g., 10 g L − 1 ) and full ventilation are recommended for producing high quality and vigorous pistachio plantlets under in vitro conditions.

We used brightfield and epifluorescence microscopy, as well as permeability tests, to investigate the apoplastic histochemical features of plant roots associated with ion hyperaccumulation, invasion, and tolerance of oligotrophic conditions. In hyperaccumulator species with a hypodermis (exodermis absent), ions penetrated the root apex, including the root cap. By contrast, in non-hyperaccumulator species possessing an exodermis, ions did not penetrate the root cap. In vivo , the lignified hypodermis blocked the entry of ions into the cortex, while root exodermis absorbed ions and restricted them to the cortex. The roots of the hyperaccumulators Pteris vittata and Cardamine hupingshanensis , as well as the aquatic invasives Alternanthera philoxeroides , Eichhornia crassipes , and Pistia stratiotes, contained lignin and pectins. These compounds may trap and store ions before hypodermis maturation, facilitating ion hyperaccumulation and retention in the apoplastic spaces of the roots. These apoplastic histochemical features were consistent with certain species-specific characters, including ion hyperaccumulation, invasive behaviors in aquatic environments, or tolerance of oligotrophic conditions. We suggest that apoplastic histochemical features of the root may act as invasion mechanisms, allowing these invasive aquatic plants to outcompete indigenous plants for ions.

Current problems with sewage sludge (SS) disposal could be solved by application to agricultural land considering its fertilizer properties and ability to improve soil condition. However, SS may contain heavy metals as well as pathogenic microorganisms. In this study, molecular analysis of partial 18S rRNA gene was used to study the impact of SS application into the soil on the genetic diversity of fungal communities, especially arbuscular mycorrhizal fungi in the rhizosphere and roots of barley. These samples were collected on three dates from the control soil without SS and from the soil with the addition of SS at the concentrations of 5 and 15 t ha −1 . Fungal alpha diversity in the rhizosphere of barley was affected by SS differently than in barley roots. In addition, principal component analysis and cluster analysis revealed that fungal communities were strongly influenced by the SS addition into the soil, sample type, and the sampling date. This approach was complemented by an evaluation of the basic parameters of barley production and the response of these parameters to the presence of SS in the soil. The plant height increased with increasing SS concentration and the thousand seed weight significantly increased at the concentration of 5 t ha −1 SS but significantly decreased in 15 t ha −1 .

Coronaviruses have spread widely among humans and other animals, but not all coronaviruses carried by specific animals can directly infect other kinds of animals. Viruses from most animal hosts need an intermediate host before they can spread widely among humans. Under natural conditions, coronaviruses do not rapidly change from infecting wild animals as intermediate hosts and to spreading widely among humans. The intermediate host might be the animals captured or bred for the purpose of cross-breeding with domesticated species for improvement of the breed. These animals differ from wild animals at the environmental and genetic levels. It is an important direction to study the semi-wild animals domesticated by humans in search for intermediate hosts of viruses widely spread among humans.

Aquatic macro-invertebrates play a vital role in the food chain of river ecosystem at several trophic guilds and consumer levels, and are used as biomonitoring tools for aquatic ecosystem health. However, hydrologic conditions of these ecosystems have been severely altered because of the increase in urban development and agricultural expansion. This study examined benthic invertebrate response to processes that structure their community in the Wewe River, segmented into intact, medium, and severe condition zones. We sampled in 100 stations in a period of 4 months in the wet (June–September, 2019) and 3 months in the dry (January–March, 2020) seasons. Geometric series, rarefaction, and Hill numbers models were used to quantify invertebrate assemblages, while ordination technique, canonical correspondence analysis, was used to evaluate the influence of predictive factors on their assemblages. A total of 2,075 individuals belonging to 20 family taxa were registered. There was no significant difference in benthic assemblages between the dry and wet seasons. Predictive factors accounted for 47.04 and 50.84% variances, respectively. Taxa distribution patterns differed significantly only in the severely disturbed zone during the wet season. Neptidae, Libellulidae, and Chironomidae were the most abundant taxa, indicating their broad range habitat preference and their ability to adapt to seasonal changes. Asellidae and Perlidae were the least detected, suggesting their sensitivity to elevated levels of some water quality parameters. The findings highlight the threats to the benthic community and overall functional state of the Wewe River, with the need to consider the proposed conservation interventions indicated in this study.

The entomopathogenic fungus T011, parasitizing on nymph of Cicada, collected in the coffee garden in Dak Lak Province, Vietnam, was preliminarily morphologically identified as Isaria cicadae , belonged to order Hypocreales and family Clavicipitaceae. To ensure the authenticity of T011, phylogenetic analysis of the concatenated set of multiple genes including ITS , nrLSU , nrSSU , Rpb1 , and Tef1 was applied to support the identification. Genomic DNA was isolated from dried sample T011. The PCR assay sequencing was applied to amplify ITS , nrLSU , nrSSU , Rpb1 , and Tef1 gene. For phylogenetic analysis, the concatenated data of both target gens were constructed with MEGAX with a 1,000 replicate bootstrap based on the neighbor-joining, maximum likelihood, maximum parsimony method. As the result, the concatenated data containing 62 sequences belonged to order Hypocreales, families Clavicipitaceae, and 2 outgroup sequences belonged to order Hypocreales, genus Verticillium . The phylogenetic analysis results indicated that T011 was accepted at subclade Cordyceps and significantly formed the monophyletic group with referent Cordyceps cicadae (Telemorph of Isaria cicadae ) with high bootstrap value. The phylogenetically analyzed result was strongly supported by our morphological analysis described as the Isaria cicadae . In summary, phylogenetic analyses based on the concatenated dataset were successfully applied to strengthen the identification of T011 as Isaria cicadae .

Understanding the response of biomass allocation in current-year twigs is crucial for elucidating the plant life-history strategies under heterogeneous volcanic habitats. We aimed to test whether twig biomass allocation, within-leaf biomass allocation, and the size-number trade-off of Betula platyphylla would be influenced. We measured twig traits of B. platyphylla in Wudalianchi volcanic kipuka, the lava platform, and Shankou lake in northeastern China using standardized major axis analyses. The results showed that the leaf number, total lamina mass (TLAM), stem mass (SM), and twig mass (TM) were significantly different between the three habitats and were greatest in kipuka with abundant soil nutrients. TLAM and SM scaled allometrically with respect to TM, while the normalization constants of the lava platform differ significantly between kipuka and Shankou lake, which showed that under certain TM, leaves gain more biomass in the lava platform. However, within the leaf, individual lamina mass (ILM) scaled isometrically with respect to individual petiole mass (IPM) in kipuka and the lava platform, but ILM scaled allometrically to IPM in Shankou lake. Our results indicated that inhabitats influenced the twig traits and biomass allocation and within-leaf biomass allocation are strategies for plants to adapt to volcanic heterogeneous habitats.

This study aims to investigate the effects of commercial probiotic supplementation in water on the performance parameters, carcass traits, immune function, and antioxidant capacity of broiler chicks. In the experiment, 120 Arbor Acres (AA) broilers (60 male and 60 female) were randomly allocated into four groups (G) – G1: basal diet and G2, G3, and G4: basal diet with 1% Lactobacillus casei , 1% L. acidophilus , and 1% Bifidobacterium in the water, lasting 42 days. The experimental results revealed that probiotic additives produced positive impacts on body weight, average daily feed intake (ADFI), and average daily weight gain for female chicks, whereas these probiotics significantly reduced ADFI and the feed conversion ratio of male chicks ( P < 0.05). Probiotics efficiently improved eviscerated yield and breast yield while reducing the abdominal fat ( P < 0.05) for the male broiler chicks. A marked increase was observed in the weight of the spleen, bursa of Fabricius, and thymus in the treatment group ( P < 0.05). Besides, probiotics produced a significant effect on the concentrations of immune-related proteins ( P < 0.05) and markedly increased the concentrations of antioxidase and digestive enzymes when compared with the control ( P < 0.05). The addition of probiotics dramatically reduced the total counts of Escherichia coli and Salmonella and increased the quantity of Lactobacilli ( P < 0.05). The results of the present study demonstrated an increase in growth performance, carcass traits, immune function, gut microbial population, and antioxidant capacity by supplementing 1% probiotics ( L. casei , L. acidophilus , and Bifidobacterium ) in the water for broilers.

Marchalina hellenica is a sap sucking scale insect endemic to the Aegean basin and it has been introduced to several regions in Greece and Turkey to increase pine honey production. It is also considered as a pest since heavy infestation may leave the host trees vulnerable to secondary pests. An understanding of its natural predators would facilitate planning biocontrol programs. Although there are several studies reporting the predators of M. hellenica in its native range, there is no study identifying those in its introduced range. We aimed to determine predators of M. hellenica in Burdur, one of its introduced sites in Turkey. We carried out sampling through regular visits in an M. hellenica -infested locality nearby Burdur Lake. Through field and laboratory observations, we identified 19 species predating upon M. hellenica . Comparing predators reported in previous studies in its native range and those we found in the present study showed that 12 of the species that we found are new reports for the species predating upon M. hellenica . The highest number of predator individuals belonged to the monophagous Neoleucopis kartliana . Myrrha octodecimguttata , Chilocorus bipustulatus and Harmonia quadripunctata were also the most frequently observed predators.

Wound healing is a complex process with many interdependent pathophysiological and immunological mediators to restore the cellular integrity of damaged tissue. Cutaneous wound healing is the repair response to a multitude of pathologies induced by trauma, surgery, and burn leading to the restoration and functionality of the compromised cells. Many different methods have been employed to treat acute and chronic wounds, such as antimicrobial therapy, as most wounds are susceptible to infection from microbes and are difficult to treat. However, many antimicrobial agents have become ineffective in wound treatment due to the emergence of multiple drug-resistant bacteria, and failures in current wound treatment methods have been widely reported. For this reason, alternative therapies have been sought, one of which is the use of honey as a wound treatment agent. The use of honey has recently gained clinical popularity for possible use in wound treatment and regenerative medicine. With this high demand, a better delivery and application procedure is required, as well as research aiming at its bioactivity. Honey is a safe natural substance, effective in the inhibition of bacterial growth and the treatment of a broad range of wound types, including burns, scratches, diabetic boils (Skin abscesses associated with diabetic), malignancies, leprosy, fistulas, leg ulcers, traumatic boils, cervical and varicose ulcers, amputation, burst abdominal wounds, septic and surgical wounds, cracked nipples, and wounds in the abdominal wall. Honey comprises a wide variety of active compounds, including flavonoids, phenolic acid, organic acids, enzymes, and vitamins, that may act to improve the wound healing process. Tissue-engineered scaffolds have recently attracted a great deal of attention, and various scaffold fabrication techniques are being researched. Some incorporate honey to improve their delivery during wound treatment. Hence, the aim of this review is to summarize recent studies on the wound healing properties of honey.

We intended to explore the potential molecular mechanisms underlying the cardiac conduction block inducted by urea transporter (UT)-B deletion at the transcriptome level. The heart tissues were harvested from UT-B null mice and age-matched wild-type mice for lncRNA sequencing analysis. Based on the sequencing data, the differentially expressed mRNAs (DEMs) and lncRNAs (DELs) between UT-B knockout and control groups were identified, followed by function analysis and mRNA–lncRNA co-expression analysis. The miRNAs were predicted, and then the competing endogenous RNA (ceRNA) network was constructed. UT-B deletion results in the aberrant expression of 588 lncRNAs and 194 mRNAs. These DEMs were significantly enriched in the inflammation-related pathway. A lncRNA–mRNA co-expression network and a ceRNA network were constructed on the basis of the DEMs and DELs. The complement 7 (C7)–NONMMUT137216.1 co-expression pair had the highest correlation coefficient in the co-expression network. NONMMUT140591.1 had the highest degree in the ceRNA network and was involved in the ceRNA of NONMMUT140591.1-mmu-miR-298-5p- Gata5 (GATA binding protein 5). UT-B deletion may promote cardiac conduction block via inflammatory process. The ceRNA NONMMUT140591.1-mmu-miR-298-5p- Gata5 may be a potential molecular mechanism of UT-B knockout-induced cardiac conduction block. Graphical abstract

Hydatidosis is an endemic disease causing a severe threat to public health. Drugs and surgery have been utilized for treatment, but their efficiency is not adequate. Therefore, new methods are required for treating such diseases. In this study, we attempt to evaluate the efficiency of radiotherapy for hydatidosis in sheep. The sheep naturally infected with pulmonary hydatid were randomly divided into four groups, including the control group subjected to no irradiation and the other three groups subjected to 30, 45, and 60 Gy irradiation, respectively. Gene expression of caspase-3 and gadd45a and protein expression of BCL-2 and BAX in the lung tissues were evaluated after treatment. Our data showed that the irradiation with a dose of 30, 45, and 60 Gy significantly induced the expression of caspase-3 and gadd45a . Immunohistochemical staining showed that the BCL-2 protein was downregulated after exposure to 45 Gy of irradiation, whereas the BAX expression was downregulated after irradiation at a dose of 45 and 60 Gy, respectively. On this basis, we speculated that 45 Gy might be a safe and effective dose for treating pulmonary hydatidosis in sheep, which induced lower expression of caspase-3 and gadd45a in the cyst and a downregulation of BCL-2 and BAX in the adjacent lung tissues.

This study demonstrated the effect of positional isomerism of benzoic acid derivatives against E. coli ATCC 700728 with the serotype O157. The addition of hydroxyl and methoxyl substituents weakened the effect of acids against E. coli with respect to benzoic acid (except 2-hydroxybenzoic). The connection of the hydroxyl group at the second carbon atom in the benzoic ring reduced the time needed to kill bacterial cells. Phenolic acids with methoxyl substitutes limited the biofilm formation by E. coli to a greater extent than hydroxyl derivatives. The most significant influence on the antibacterial activity of phenolic acids has the type of substituent attached to the benzoic ring, their number, and finally the number of carbon atoms at which the functional group is located.

Background This study aimed to find the correlation of Gensini score with retinal vessel diameter and arteriovenous ratio in elderly patients with coronary heart disease (CHD). Methods This study included 120 senile CHD patients as the CHD group and 100 healthy individuals as the normal group (NG). Gensini score was used to evaluate the severity of coronary artery lesions. Central retinal artery equivalents (CRAE), central retinal venular equivalents (CRVE), and arteriovenous ratio (AVR) were measured. Results CHD group has lower CRAE and AVR than NG, while higher CRVE was observed in NG. CRAE and AVR in UAP (unstable angina pectoris) and AMI (acute myocardial infarction) groups showed reduction (stable angina pectoris); however, enhanced CRVE and Gensini scores in UA and AMI groups were observed as compared to the SAP group. CRAE and AVR in moderate and severe groups were reduced to a greater extent compared to the mild groups, while enhanced CRVE and Gensini scores were observed more often in the severe group than the mild group. CRAE and AVR were negatively correlated with the Gensini score; however, CRVE was positively correlated with the Gensini score. Conclusion AVR is expected to be a noninvasive index to diagnose and predict senile CHD, which has a certain evaluation value. Diabetes, smoking history, and TC are independent risk factors of senile CHD.

This research aimed to describe the functions of vascular endothelial cells (VECs) in protecting target organs and the anti-atherosclerotic effects of different enantiomers of amlodipine on a rabbit model of atherosclerosis. Thirty male New Zealand white rabbits were randomly allocated to four groups (nA = 9, nB = 7, nC = 7, and nD = 7 rabbits): rabbits in group-A (control group) were fed a high-fat diet, group-B rabbits were fed a high-fat diet plus 2.5 mg/kg/day S-amlodipine, group-C rabbits were fed a high-fat diet plus 2.5 mg/kg/day R-amlodipine, and group-D rabbits were fed a high-fat diet plus 5 mg/kg/day racemic amlodipine. Different enantiomers of amlodipine did not influence lipid profiles and serum level of eNOS in the rabbit atherosclerosis model but decreased ET-1 expression to some extent. The serum NO and iNOS levels in the drug intervention groups were significantly reduced. No significant differences in the rabbits’ body weights were observed. At the 4th and 8th weeks, the serum lipid profiles significantly increased in high cholesterol diet groups. The serum ET-1 level was significantly increased in each group of rabbits at the 8th week. Both S-amlodipine and R-amlodipine may protect the endothelium by reducing the serum ET-1 level, downregulating iNOS expression.

The term fatty keratopathy is used to describe the phenomenon of fat deposition caused by corneal neovascularization, which will severely affect the eye’s beauty and vision. The purpose of this study was to establish a New Zealand white rabbit animal model of fatty keratopathy, that is, the establishment of an animal model of fatty keratopathy. The goal was achieved by the combination of a corneal neovascularization animal model and a hyperlipidemia animal model. Two groups were created according to the experimental sequence. The first group initially induced a corneal neovascularization pattern and later induced a hyperlipidemia pattern, and the second group followed the opposite sequence. The results of the two groups showed that all the significant crystalline deposits of the cornea were visible. So the animal models of fatty keratopathy were successfully established in both groups.

The purpose of this study is to observe the potential value and underlying mechanism of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-143 axis in ISR. A total of 150 participants were enrolled, including 100 patients (observation group) with coronary heart disease who underwent stent implantation in the Department of Cardiology of our hospital between January 2018 and January 2020, and 50 healthy people (control group) concurrently underwent a physical examination. Serum MALAT1 and miR-143 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Tumor necrosis factor-α (TNF-α; 10 ng/mL) induced human vascular smooth muscle cells (HVSMCs). MALAT1 increased while miR-143 decreased in the observation group versus the control group ( P < 0.001). The non-restenosis group had significantly elevated MALAT1 expression while decreased miR-143 expression than the restenosis group ( P < 0.001). The areas under the curves of the expression of MALAT1 and miR-143 in predicting restenosis were 0.917 and 0.881, respectively. Following si-MALAT1 transfection, HVSMC multiplication and invasiveness decreased significantly ( P < 0.05). miR-143-inhibitor was observed to upregulate the luciferase activity of MALAT1-WT ( P < 0.05). MALAT1 is highly expressed in patients with ISR while miR-143 is decreased, and the MALAT1/miR-143 axis is a potential pathway to modulate the multiplication and invasiveness of HVSMCs.