Startseite lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
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lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation

  • Liting Wu , Bingjing Gao , Mengyuan Shen , Lu Wei , Zhumeng Li und Wenfang Zhuang EMAIL logo
Veröffentlicht/Copyright: 14. November 2023

Abstract

miR-378 is known to suppress myocardial fibrosis, while its upstream regulators have not been identified. lncRNA LENGA is a recently identified lncRNA in cancer biology. We observed the altered expression of LENGA in atrial fibrillation (AF) patients and predicted its interaction with miR-378. We then explored the interaction between LENGA and miR-378 in AF. Angiotensin-II (Ang-II)-induced human atrial cardiac fibroblasts and human atrial muscle tissues were collected and the expression of LENGA and miR-378 was determined by RT-qPCR. The interaction between LENGA and miR-378 was analyzed through bioinformatics analysis and confirmed by RNA pulldown assay. Cell proliferation and collagen production were analyzed through in vitro assay to analyze the role of LENGA and miR-378 in MF. AF patients showed increased expression of LENGA and deceased expression of miR-378 compared to the sinus rhythm group. LENGA and miR-378 interacted with each other, while they are not closely correlated with each other. Overexpression assay showed that LENGA and miR-378 overexpression failed to affect each other’s expression. LENGA promoted collagen production and proliferation of Ang-II-induced atrial fibroblasts, while miR-378 played opposite roles. Moreover, LENGA suppressed the function of miR-378. Therefore, LENGA may sponge miR-378 to promote MF in AF.

1 Introduction

Atrial fibrillation (AF), also called AF or AFib, is an upper ventricular rapid arrhythmia, accompanied by uncoordinated atrial electrical activity and the resulting ineffective atrial contraction [1,2]. Without proper control and treatment, AF often causes the formation of blood clots in the heart [3]. It is estimated that AF is affecting about 1% of the population worldwide, and its incidence is predicted to be significantly increased by 2050 [4,5,6]. The crude mortality of AF is about 70.7 per 100,000 person per year [7,8]. Patients with AF are usually treated with certain therapies to reset the heart rhythm, medications to prevent and treat blood clots, and catheter procedures [9]. However, treatment outcomes in many cases are still unsatisfactory and the mortality is unacceptably high [9]. Therefore, novel therapies are still needed.

Understanding the molecular mechanism underlying the initiation and development of AF is the key for the development of AF. Patients with AF experience pathological changes in atrial myocardium, such as glycogen accumulation, mitochondrial abnormalities, loss of sarcomeres, and increased cardiomyocyte volume [10,11]. Atrial structural remodeling in AF patients is characterized by atrial fibrosis, which is caused by dysregulated atrial fibroblast proliferation and the increased extracellular matrix deposition [10,11]. Therefore, regulating the proliferation of atrial fibroblast may contribute to the recovery of AF.

Previous studies have characterized a big number of non-coding RNAs involved in the development of AF [12,13,14], and some of these RNAs are potential targets to treat AF [14,15,16]. For example, lncRNA PVT1 regulates atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in AF [17]. lncRNA-LINC00472 contributes to the pathogenesis of AF by reducing the expression of JP2 and RyR2 via miR-24 [18]. Moreover, microRNAs (miRNAs) are endogenous ∼23-nt RNAs that can complementarily bind to messenger RNAs (mRNAs) of protein-coding genes and lead to their regulation post-transcriptionally [19,20]. Most published studies have focussed on their effect on the immune system or in cancer, while only a few reported their role in cardiovascular disease [21,22,23,24]. For instance, miR-378 has been reported to suppress myocardial fibrosis [25]. However, upstream regulators of miR-378 in this process are unknown. lncRNA LENGA is a recently identified lncRNA in cancer biology [26], which acts as a tumor suppressor in gastric cancer through BRD7/TP53 signaling [26]. We observed the altered expression of LENGA in AF patients and predicted its interaction with miR-378. We then explored the interaction between LENGA and miR-378 in AF.

2 Materials and methods

2.1 Patients and tissue samples

Research subjects of the present study included the (AF, n = 37) group and sinus rhythm group (SR, n  =  32). All these patients received surgeries of heart valve replacement between May 2020 and May 2022 at Shidong Hospital Affiliated to University of Shanghai for Science and Technology after Ethics Committee of this hospital approved this study. Subsequently, peripheral blood samples were collected from all subjects to measure their expression of Collagen I, Collagen III, miR-378 and LENGA. In addition, cardiac tissue samples were collected from the left atrial free wall near the interatrial septum in both AF patients (the AF group, N = 37) and healthy subjects (the control group, N = 32) to measure the expression of Collagen I, Collagen III, miR-378, and LENGA in tissue samples. All of these patients signed informed consent. Research subjects of this study excluded the ones with a history of hyperthyroidism, infective endocarditis, coronary atherosclerotic heart disease, liver and kidney dysfunction, and chronic pulmonary heart disease. During surgery, patients’ atrial muscle tissues were collected and stored in liquid nitrogen. Clinical data of SR and AF groups are presented in Table 1.

Table 1

Clinical data of AF and SR groups

AF (n = 37) SR (n = 32)
Age 52.3 ± 10.8 53.1 ± 13.1
Male gender 18 16
NYHA classification
I/II 4 3
III 25 24
IV 8 5
SBP (mm Hg) 120.19 ± 11.12 115.19 ± 11.09
DBP (mm Hg) 75.82 ± 11.11 72.12 ± 8.37
LAD (cm) 4.67 ± 0.29* 3.12 ± 0.11
RAD (cm) 3.66 ± 0.31 3.50 ± 0.31
LVEF (%) 55.21 ± 2.99 57.03 ± 3.11

*P < 0.05.

2.2 Human atrial cardiac fibroblasts and cell culture

Human atrial cardiac fibroblasts, which were cryopreserved at passage one, were purchased from Innoprot (Biscay, Spain). Cells were cultivated in Fibroblast Medium-2 (P60108-2, Innoprot) at 37°C (95% humidity and 5% CO2). Cells were collected from passage three to five for further applications.

2.3 Cell transfection

Overexpression vector of LENGA was established with pcDNA3.1 as a backbone. Mimic of miR-378 (5′ACUGGACUUGGAGUCAGAAGGC-3′) and negative control (NC) miRNA were designed and synthesized by Sangon (Shanghai, China). Human atrial cardiac fibroblasts collected from passage three to five were used to prepare single cell suspensions, which were transfected with the vector-expressing LENGA and/or miR-378 mimic using Lipofectamine™ 2000 Transfection Reagent (Invitrogen). Transfections were conducted following manufacturer’s instruction. Cells were harvested at 48 h post-transfection to isolate total RNA samples, which were used in RT-qPCR to check the efficiency of transfections.

2.4 RNA isolation

Human atrial cardiac fibroblasts and atrial muscle tissues were subjected to RNA isolation using TRIzol reagent (Invitrogen). Briefly, cells were harvested and tissue samples were used to prepare tissue powder in liquid nitrogen. Then, TRIzol reagent was mixed with the harvested cells or tissue samples to a ratio of 10 to 1. Chloroform purification was performed twice to remove protein contamination. Phenol precipitation was down to collect RNA. RNA samples were analyzed using Bioanalyzer. DNase I digestion was performed to completely remove DNA contamination.

2.5 RT-qPCR

SSRT IV kit (Invitrogen) was used to prepare cDNA samples with total RNA samples as template. SYBR Green PCR Mix (TaKaRa) was then used to prepare qPCR mixture. qPCR was performed on CFX Opus 96 Real-Time PCR System (Bio-Rad) to determine the expression levels of Collagen I, Collagen III, LENGA and miR-378. The method of 2−ΔΔCt was used to analyze Ct values to calculate the fold changes of gene expression levels.

2.6 BrdU assay analysis of cell proliferation

A BrdU kit (Abcam, Cambridge, MA, USA) was applied to determine the proliferation of human atrial cardiac fibroblasts. Cells were collected at 48 h post-transfection and further cultivated in fresh medium containing 1 μM Angiotensin-II (Ang-II) (Sigma-Aldrich, St. Louis, MO, USA) for 24 h. After that, cells were stained with BrdU for 1 h, followed by incubation with anti-BrdU antibody for 1 h. To quantify cell proliferation, OD values at 450 nm were measured.

2.7 RNA pulldown assay

RNA transcripts of LENGA and NC were prepared using HiScribe T7 In Vitro Transcription Kit (E2030, NEB). Biotin labeling at the 3′ end was performed using Pierce™ RNA 3′ End Biotinylation Kit. Cell lysates were prepared using human atrial cardiac fibroblasts and incubated with Biotin labeled LENGA and NC RNAs at 25°C for 1 h. Streptavidin agarose beads (Invitrogen) were then used to pulldown RNA complexes. RNA complexes were purified using TRIzol (Invitrogen), followed by RT-qPCR to determine the expression of miR-378.

2.8 Statistical analysis

GraphPad Prism 6 software was used to perform all statistical analyses. Data were expressed as mean ± standard deviation values of three biological replicates or average values of three technical replicates and were compared by unpaired t test and One-way analysis of variance, respectively. Correlations were analyzed using Pearson’s correlation coefficient. p  <  0.05 was statistically significant.

  1. Ethics approval and consent to participate: This study was approved by Ethics Committee of the Shidong Hospital Affiliated to University of Shanghai For Science and Technology. The study followed the tenets of the Declaration of Helsinki, and informed written consent was obtained from all patients and controls after we explained the nature and possible consequences of the study.

3 Results

3.1 Analysis of Collagen I, Collagen III, LENGA, and miR-378 expression in AF and SR groups

Expression of Collagen I and Collagen III mRNA, as well as LENGA and miR-378 was determined through RT-qPCR in both AF and SR groups. Compared to SR group. The AF group showed significantly increased expression of both Collagen I (Figure 1a, p < 0.01) and Collagen III (Figure 1b, p < 0.01) mRNAs. Moreover, AF patients showed increased expression of LENGA (Figure 1c, p < 0.01) and deceased expression of miR-378 (Figure 1d, p < 0.01) compared to the SR group. Therefore, altered expression of Collagen I, Collagen III, LENGA, and miR-378 are likely participate in AF.

Figure 1 
                  Analysis of Collagen I, Collagen III, LENGA, and miR-378 expression in AF and SR groups. Expression of Collagen I (a) and Collagen III (b) mRNA, as well as LENGA (c) and miR-378 (d), was determined through RT-qPCR in both AF and SR groups. Data were expressed as average values of three qPCR replicates. **p < 0.01.
Figure 1

Analysis of Collagen I, Collagen III, LENGA, and miR-378 expression in AF and SR groups. Expression of Collagen I (a) and Collagen III (b) mRNA, as well as LENGA (c) and miR-378 (d), was determined through RT-qPCR in both AF and SR groups. Data were expressed as average values of three qPCR replicates. **p < 0.01.

3.2 LENGA showed a negative correlation to Collagen I and Collagen III mRNA in AF samples, but not in SR samples

The correlations of LENGA to Collagen I and Collagen III mRNA across AF samples and SR samples were analyzed by Pearson’s correlation coefficient. Across AF samples, LENGA was positively and significantly correlated with both Collagen I mRNA (Figure 2a) and Collagen III mRNA (Figure 2b). Across SR samples, LENGA showed no close correlation to Collagen I (Figure 2c) and Collagen III mRNA (Figure 2d). And we also detected that COL1A1 and MM9 (they are fibrotic marker) expression level was increased in the AF groups comparing to the SR groups (Figure 2e). In addition, the collagen volume fraction is more augmented in the AF groups than in the SR groups (Figure 2f). Therefore, LENGA may affect Collagen I and Collagen III in AF to affect disease progression.

Figure 2 
                  LENGA showed a negative correlation to Collagen I and Collagen III mRNA in AF samples, but not in SR samples. The correlations of LENGA with Collagen I (a) and Collagen III (b) mRNA across AF samples were analyzed by Pearson’s correlation coefficient. The same method was applied to analyze the correlations of LENGA with Collagen I (c) and Collagen III (d) mRNA across SR samples. Western blot analysis showed protein expression of MMP9 and COL1A1 in the AF and SR groups (e). Histopathological changes and the collagen volume fraction in left atrium after staining with Masson’s trichrome stain in the AF and SR groups (f). **p < 0.01.
Figure 2

LENGA showed a negative correlation to Collagen I and Collagen III mRNA in AF samples, but not in SR samples. The correlations of LENGA with Collagen I (a) and Collagen III (b) mRNA across AF samples were analyzed by Pearson’s correlation coefficient. The same method was applied to analyze the correlations of LENGA with Collagen I (c) and Collagen III (d) mRNA across SR samples. Western blot analysis showed protein expression of MMP9 and COL1A1 in the AF and SR groups (e). Histopathological changes and the collagen volume fraction in left atrium after staining with Masson’s trichrome stain in the AF and SR groups (f). **p < 0.01.

3.3 LENGA and miR-378 interacted with each other, but showed no role in each other’s expression

Based on intaRNA 2.0 prediction, the sequences of LENGA and miR-378 may form multiple base pairs (Figure 3a). RNA pulldown assay was performed to verify this interaction. Compared to the Bio-NC pulldown group, the Bio-LENGA pulldown group showed significantly increased levels of miR-378 RNA accumulation, further confirming the interaction between them (Figure 3b, p < 0.01). The correlations between LENGA and miR-378 across AF (Figure 3c) and SR (Figure 3d) samples were analyzed by Pearson’s correlation coefficient. Interestingly, they are not closely correlated with each other across these samples. LENGA and miR-378 were overexpressed in human atrial cardiac fibroblasts (Figure 3e). Overexpression and knock down assay showed that LENGA and miR-378 overexpression failed to affect each other’s expression (Figure 3f and g).

Figure 3 
                  LENGA and miR-378 interacted with each other but showed no role in each other’s expression. IntaRNA 2.0 was used to predict the interaction between LENGA and miR-378 (a), which was confirmed by RNA pulldown assay (b). The correlations between LENGA and miR-378 across AF (c) and SR (d) samples were analyzed by Pearson’s correlation coefficient. LENGA and miR-378 were overexpressed in human atrial cardiac fibroblasts (e), and the role of LENGA and miR-378 in each other’s expression was also analyzed by RT-qPCR (f). Knocked down LENGA in human atrial cardiac fibroblasts first, then check the expression of miR-378 (g). **p < 0.01.
Figure 3

LENGA and miR-378 interacted with each other but showed no role in each other’s expression. IntaRNA 2.0 was used to predict the interaction between LENGA and miR-378 (a), which was confirmed by RNA pulldown assay (b). The correlations between LENGA and miR-378 across AF (c) and SR (d) samples were analyzed by Pearson’s correlation coefficient. LENGA and miR-378 were overexpressed in human atrial cardiac fibroblasts (e), and the role of LENGA and miR-378 in each other’s expression was also analyzed by RT-qPCR (f). Knocked down LENGA in human atrial cardiac fibroblasts first, then check the expression of miR-378 (g). **p < 0.01.

3.4 The role of LENGA in collagen production and cell proliferation was affected by miR-378

The roles of LENGA and miR-378 in regulating the expression of Collagen I and Collagen III mRNA as well as the proliferation of Ang-II-induced atrial fibroblasts were analyzed by RT-qPCR and BrdU assays, respectively. LENGA promoted collagen production (Figure 4a, p < 0.01) and proliferation of Ang-II-induced atrial fibroblasts (Figure 4b, p < 0.01), while miR-378 played opposite roles. Moreover, LENGA suppressed the function of miR-378.

Figure 4 
                  The role of LENGA in collagen production and cell proliferation was affected by miR-378. The roles of LENGA and miR-378 in regulating the expression of Collagen I and Collagen III mRNA (a and b) were analyzed by RT-qPCR as well as the proliferation of Ang-II-induced atrial fibroblasts were detected by BrdU assays (c), respectively. **p < 0.01.
Figure 4

The role of LENGA in collagen production and cell proliferation was affected by miR-378. The roles of LENGA and miR-378 in regulating the expression of Collagen I and Collagen III mRNA (a and b) were analyzed by RT-qPCR as well as the proliferation of Ang-II-induced atrial fibroblasts were detected by BrdU assays (c), respectively. **p < 0.01.

4 Discussion

The present study explored the involvement of LENGA and miR-378 in AF. We reported the altered expression of LENGA and miR-378 in AF, and their roles in regulating the expression of Collagen I and Collagen III and the proliferation of Ang-II-induced atrial fibroblasts. The potential interaction between these two ncRNAs has also been explored.

In a recent study, LENGA has been characterized as an lncRNA with tumor suppressor in gastric cancer, in which LENGA was downregulated and its overexpression interacts with BRD7/TP53 signaling to suppress tumor metastasis and growth [26]. To our best knowledge, the involvement of LENGA in other diseases has not been explored. The present study reported the increased expression of LENGA in AF. Moreover, LENGA shows a close correlation to Collagen I and Collagen III. Collagen turnover is involved in the perpetuation and generation of AF [27]. In the present study, overexpression of LENGA resulted in the increased expression of both Collagen I and Collagen III at mRNA level in atrial fibroblasts. Meanwhile, overexpression of LENGA also promoted the proliferation of Ang-II-induced atrial fibroblasts. Therefore, LENGA may affect collagen turnover and the proliferation of atrial fibroblasts to induce AF.

miRNAs have been reported to regulate many cell biological functions. In respect to AF, many miRNAs including miR-21, miR-29, miR-106b-25, miR-126, miR-409-3p, and miR-432 were reported to be involved in the pathogenesis of AF [18]. Moreover, miR-378 is known to inhibit myocardial fibrosis by a paracrine mechanism in mouse model [25]. However, its involvement in AF is unknown. Hence, in this study, miR-378 was found to be downregulated in patients with AF, and its overexpression suppressed the expression of both Collagen I and Collagen III in atrial fibroblasts. In addition, miR-378 also suppress the proliferation of Ang-II-induced atrial fibroblasts. Our study indicated the protective role of miR-378 in patients with AF.

Interestingly, LENGA was found to direct interact with miR-378, while they are not closely correlated with each other. Moreover, overexpression experiments showed that miR-378 and LENGA failed to affect the expression of each other. Interestingly, LENGA suppressed the role of miR-378 in the proliferation of Ang-II-induced atrial fibroblasts and the production of Collagen I and Collagen III mRNA in atrial fibroblasts. Therefore, LENGA may serve as an endogenous competing RNA for miR-378 to suppress its protective role in AF.

In summary, LENGA is overexpressed in AF and miR-378 is downregulated in AF. LENGA sponges miR-378 to promote the proliferation of Collagen I and Collagen III and increased the proliferation of Ang-II-induced atrial fibroblasts, thereby promoting the development of AF. LENGA and miR-378 are dysregulated in AF patients, thus leading to the conclusion that they can be used as potential biomarkers or therapeutic targets of AF.

Acknowledgements

Not applicable.

  1. Funding information: We thank the financial support from Key Disciplines in Yangpu District (No. 22YPZB03).

  2. Conflict of interest: The authors reported no potential conflict of interest.

  3. Data availability statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-05-24
Revised: 2023-09-07
Accepted: 2023-09-29
Published Online: 2023-11-14

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
Heruntergeladen am 9.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0831/html
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