Home Circular RNAs as potential biomarkers for male severe sepsis
Article Open Access

Circular RNAs as potential biomarkers for male severe sepsis

  • Liang Jun , Zhonghua Wang , Shouhong Wang , Xiaolong Liao , Tiehe Qin and Weixin Guo EMAIL logo
Published/Copyright: July 24, 2024

Abstract

Circular RNAs (circRNAs) play important roles in many human diseases. However, their role in the development of severe sepsis, a condition that remains one of the main causes of death in intensive care units, has not yet been defined. In this study, we interrogated the molecular mechanisms of circRNAs in severe sepsis. We profiled the expression levels of 5,680 circRNAs in plasma extracted from blood samples of 9 severe sepsis cases or 9 controls (male, age 78 ± 7) using the Human circRNA Array. To enrich protein-coding genes hosting severe sepsis-related circRNAs, we conducted gene ontology and pathways analyses. Out of the identified 760 differentially expressed circRNAs, 404 were upregulated while 356 were downregulated (fold change [FC] ≥2 or ≤−2, and false discovery ratio <0.05). Circ-0008285 (located in exons of CDYL), showed significant upregulation in severe sepsis with an FC of 13.7, and Bonferroni-corrected P < 0.05/5. In silico analysis identified Circ-0008285 interacting microRNAs as well as protein-coding genes. We systematically investigated the differential expression pattern of circRNAs in severe sepsis. The circRNAs we identified might serve as potential biomarkers for diagnosis and prognosis of sepsis.

1 Introduction

Sepsis is a life-threatening complication caused by the body’s extreme immune response to an infection [1]. Severe sepsis is triggered by infection combined with organ failure and hemodynamic instability. Severe sepsis occurs when there are incidences of organ failure, and remains one of the main causes of death in intensive care units [2,3]. Furthermore, a combination of severe sepsis and extreme hypotension leads to septic shock. Recently, genetic studies identify genetic loci and candidate genes associated with sepsis susceptibility. For example, rs5743708 in TLR2, rs1800629 in TNFα, and rs2569190 in CD14 increase susceptibility to sepsis or septic shock [4,5,6].

Accumulating evidence suggests that severe sepsis induces changes in many protein-coding genes [7,8] or non-coding genes [9] in human genome, such as circular RNAs (circRNAs). circRNAs are considered single-stranded RNA molecules whose 5′ and 3′ ends are covalently closed as “backsplice” to form a continuous loop [10,11,12]. Whereas circRNAs were at first identified in the cytoplasm [13], thousands of circRNAs have been shown to be expressed in many types of human cells and tissues [10,11]. Most of the circRNAs come from the exons of protein-coding genes, while relatively small proportion come from either introns or intergenic regions [14,15,16,17,18]. The circular nature of the circRNA makes them notably stable even in the presence of RNase. Accumulating evidence suggests that circRNAs play pivotal roles in many human diseases, including sepsis. For instance, Ng et al. showed that RasGEF1B could regulate the stability of mature ICAM-1 mRNAs, thus fine-tuning the immune response and protecting host cells against infection, suggesting that circRNAs play a critical role in fine-tuning immune responses [19]. An abnormal immune system is one of the crucial triggers of sepsis. Therefore, circRNAs may potentially contribute to the effective treatment of sepsis. At present, an increasing number of circRNAs have been identified as potential markers in the diagnosis and treatment of sepsis [20], such as circRNA_0075723 [21], circRNA circFADS2 [22], and exosomal hsa_circRNA_104484 and hsa_circRNA_104670 [23].

To better understand the roles of circRNAs in the pathophysiology of severe sepsis, we profiled the expression levels of 5,680 circRNAs in 9 severe sepsis cases or 9 controls using high-throughput circRNA arrays and identified differentially expressed circRNAs. Then, gene ontology (GO) and pathway analyses were performed to identify novel pathways mediating the actions of circRNAs in sepsis. In addition, we created gene interaction networks using computational tools.

2 Methods

2.1 Clinical samples

Nine severe sepsis male patients and nine age-matched controls were used initial set. The patients’ blood samples were extracted within 24 h following the diagnosis of severe sepsis. The selected patients all meet the criteria of the 2016 guidelines for severe sepsis and are over 65 years old, while excluding patients with tumors or rheumatic diseases [2]. Three blood samples were merged randomly into one testing sample. Six circRNA arrays, i.e., three for the patient sample and three for the controls were performed. For the verification of differential circRNAs, 30 severe sepsis cases and 20 controls were used to validate the highly differentially expressed circRNAs by quantitative real-time PCR (qPCR).

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration and has been approved by the Clinical Research Ethics Committee of the Guangdong General Hospital.

2.2 Plasma collection

EDTA anticoagulant tubes were used to collect blood samples. The samples were then centrifuged in an Eppendorf centrifuge at 4°C and 3,000 rpm for 15 min. The plasma was separated into 1.5 mL RNA-free EP tubes and centrifuged at 13,000 rpm for 30 min to remove cell fragments. The collected plasma was transferred into new 1.5 mL RNA-free EP tubes and stored in −80°C liquid nitrogen.

2.3 Expression of circRNA and data normalization

We analyzed the expression of 5,396 human circRNAs by Arraystar Human circRNA Array (Kangcheng Inc). Total RNA from each of the samples was quantified using a NanoDrop ND-1000 at OD260 while the quality of the RNA was assessed by electrophoresis on a denaturing agarose gel. The sample preparation and microarray hybridization were performed following Arraystar’s standard protocols. Briefly, the total RNAs were digested with Rnase R (Epicentre, Inc.) to remove linear RNAs and enrich circRNAs. Then, the enriched circRNAs were amplified and transcribed into fluorescent cRNA (Arraystar Super RNA Labeling Kit; Arraystar). The labelled circRNAs were hybridized onto the Arraystar Human circRNA Arrays (8 × 15K, Arraystar) and incubated for 17 h at 65°C in an Agilent Hybridization Oven. The slides were washed and, then, the arrays were scanned by the Agilent Scanner G2505C. Raw data were extracted and analyzed using the Agilent Feature Extraction software (version 11.0.1.1). We then normalized (Quantile) the data using GeneSpring software. Thereafter, low-intensity filtering was performed, and the circRNAs that had flags in “P” or “M” (“All Targets Value”) in at least 1 sample were retained for further analyses.

2.4 Identification of differentially expressed circRNAs

Student T-test was used to identify differentially expressed circRNAs from severe sepsis cases versus controls. The false discovery ratio (FDR) was calculated by the Benjamini–Hochberg method [24]. The differentially expressed circRNAs with FDR < 0.05 were selected as significant. Hierarchical clustering [25] was performed to show the expression pattern of significant circRNAs.

2.5 qPCR

qPCR was used to validate the expression levels of differentially expressed circRNAs. The specific primers designed for backsplice junctions of each circRNA (divergent primer) are listed in Table S1. The GAPDH gene was used as an internal control. The Ct (cycle threshold, the number of cycles required for the fluorescent signals to cross the threshold of qPCR) value of each circRNA in each sample was measured. The expression levels of circRNAs were calculated as 2−ΔCt. △Ct was defined as CtcircRNA – CtInter_ctrl. Student T-test was used to test the differential expression levels of circRNAs. Bonferroni-corrected P < 0.05 was considered significant.

2.6 GO and pathway analysis

For the differentially expressed circRNAs, topGO software [26] was used to perform GO [27], while the Kyoto Encyclopedia of Genes and Genomes (KEGG) [28] was used for pathway enrichment analysis. Fisher’s exact tests were used to find any overlap between the differentially expressed circRNAs sets and the GO terms/KEGG pathways. Benjamini-corrected FDR was set at <0.05 for the numbers of GO terms and pathways.

2.7 Data access

We deposited circRNA expression data to NCBI Gene Expression Omnibus with accession number GSE244903.

2.8 Statistical analysis for sequencing data

Agilent Feature Extraction software was used for raw data extraction. Statistical analysis of raw data was performed using the R software package. T-test was used for the differential analysis of circRNA expression. circRNAs having fold changes (FC) >2 and P-values <0.05 are selected as the significantly differentially expressed.

3 Results

3.1 Clinical characteristics

All participants included in this study were male, aged between 65 and 90 years. The initial samples included nine severe sepsis cases (age, 75 ± 8 years) and nine controls (age, 80 ± 8). The validation samples included 30 cases (age, 75 ± 7 years) and 20 controls (age, 76 ± 6). The age difference was not as significant at P > 0.05. Acute physiologic assessment and chronic health evaluation scores for the sepsis samples ranged between 23 and 35 (Table S2).

3.2 Identification of differentially expressed circRNAs in relation to severe sepsis

There were 760 differentially expressed circRNAs in sepsis versus control cases at FC ≥ 2 or ≤ −2 and FDR < 0.05. Out of the 760, 404 circRNAs were upregulated while the rest were downregulated in severe sepsis (Figure 1). The upregulated circRNAs included 364 exonic, 20 intronic, 16 intragenic, and 4 antisense circRNAs. On the other hand, the downregulated circRNAs included 306 exotic, 33 intronic, 7 intragenic, and 10 antisense circRNAs. Figure 2 shows the expression pattern for the top 40 differentially expressed circRNAs.

Figure 1 
                  Volcano plot of differentially expressed circRNAs for severe sepsis. The x-axis showed the fold changes. The positive values indicated the upregulation and the negative values indicated the downregulation of genes in severe sepsis cases. The y-axis showed the log-10 transformed P values. The red rectangle indicated the differentially expressed circRNAs at P < 0.05. The vertical lines correspond to 2-fold change up and down respectively, and the horizontal line represented a P value of 0.05.
Figure 1

Volcano plot of differentially expressed circRNAs for severe sepsis. The x-axis showed the fold changes. The positive values indicated the upregulation and the negative values indicated the downregulation of genes in severe sepsis cases. The y-axis showed the log-10 transformed P values. The red rectangle indicated the differentially expressed circRNAs at P < 0.05. The vertical lines correspond to 2-fold change up and down respectively, and the horizontal line represented a P value of 0.05.

Figure 2 
                  Heatmap of the top differentially expressed circRNAs for severe sepsis. Clustering analysis of differentially expressed circRNAs with 40 higher expression levels. circRNAs and samples were reordered by two-dimensional hierarchical clustering method, and the tree plots were the graphic representation of this process. Red color indicated upregulation and green color indicated downregulation.
Figure 2

Heatmap of the top differentially expressed circRNAs for severe sepsis. Clustering analysis of differentially expressed circRNAs with 40 higher expression levels. circRNAs and samples were reordered by two-dimensional hierarchical clustering method, and the tree plots were the graphic representation of this process. Red color indicated upregulation and green color indicated downregulation.

3.3 GO and pathway enrichment analysis

To understand biological pathways underlying the differentially expressed circRNAs in severe sepsis, we performed GO and pathway enrichment analysis. The top enriched GO terms and pathways are shown in Table 1. At FDR < 0.05, the upregulated circRNAs were enriched for genes involved in many biological processes (GO-BP terms), such as intracellular transport, primary metabolic process, and immune systems process. Besides, there was an enrichment of upregulated circRNAs involved in pathways such as insulin signally pathway and B-cell receptor signaling. On the other hand, the downregulated circRNAs were enriched for genes involved in the regulation of gene expression and many other metabolic processes. The top GO-CC terms for the upregulated circRNAs were cytoplasm, intracellular organelle part, or intracellular, while the terms for the downregulated circRNAs were nucleus or intracellular. The top GO-MF terms for the upregulated circRNAs were protein binding, ployA RNA binding, or enzyme binding, while those for the downregulated circRNAs were DNA binding, nucleic acid binding, or nucleic acid binding transcription factor activity.

Table 1

Top GO terms and pathways for differentially expressed circRNAs in sepsis

GO term/pathway Resource Fold change P value FDR
Upregulated circRNAs
Intracellular transport GO-BP 1.45 1.72 × 10−26 3.50 × 10−23
Primary metabolic process GO-BP 1.10 1.20 × 10−20 6.11 × 10−18
Immune system process GO-BP 1.31 1.98 × 10−20 8.64 × 10−18
Cytoplasm GO-CC 1.22 1.41 × 10−80 1.04 × 10−77
Intracellular organelle part GO-CC 1.30 6.63 × 10−79 2.09 × 10−76
Intracellular GO-CC 1.13 2.18 × 10−74 2.69 × 10−72
Protein binding GO-MF 1.16 3.15 × 10−49 3.50 × 10−46
Poly(A) RNA binding GO-MF 1.53 5.75 × 10−23 2.13 × 10−20
Enzyme binding GO-MF 1.39 5.08 × 10−19 1.13 × 10−16
Lysosome KEGG 11.29 5.13 × 10−12 1.51 × 10−9
Insulin signaling pathway KEGG 8.17 6.77 × 10−9 9.95 × 10−7
Regulation of actin cytoskeleton KEGG 5.67 2.13 × 10−6 8.97 × 10−5
B-cell receptor signaling pathway KEGG 5.47 3.40 × 10−6 1.11 × 10−4
Endocytosis KEGG 5.26 5.55 × 10−6 1.63 × 10−4
Downregulated circRNAs
Regulation of gene expression GO-BP 1.20 7.25 × 10−13 2.27 × 10−9
Regulation of nitrogen compound metabolic process GO-BP 1.16 7.64 × 10−10 2.02 × 10−7
RNA metabolic process GO-BP 1.16 7.95 × 10−10 2.02 × 10−7
Nucleus GO-CC 1.11 1.11 × 10−8 8.18 × 10−6
Intracellular GO-CC 1.03 2.92 × 10−5 1.08 × 10−2
DNA binding GO-MF 1.28 3.83 × 10−13 4.26 × 10−10
Nucleic acid binding GO-MF 1.17 9.64 × 10−10 5.37 × 10−7
Nucleic acid binding transcription factor activity GO-MF 1.20 3.29 × 10−4 3.66 × 10−2

3.4 Validation of the top differentially expressed circRNAs

Through reference review, we selected 9 (hsa-circ-0000267, hsa-circ-0001173, hsa-circ-0006758, hsa-circ-0008285, hsa-circ-0014879, hsa-circ-0024604, hsa-circ-0035796, hsa-circ-0001811, and hsa-circ-0084615) of the top 40 circRNAs for qPCR validation. As shown in Figure 3, the difference in circ-0008285 expression was significant.

Figure 3 
                  The expression levels of circRNAs in the replication samples. The expression levels of hsa-circ-0000267 (a), hsa-circ-0001173 (b), hsa-circ-0006758 (c), hsa-circ-0008285 (d), hsa-circ-0014879 (e), hsa-circ-0024604 (f), hsa-circ-0035796 (g), hsa-circ-0001811 (h), and hsa-circ-0084615 (i) were detected using qPCR assay. *P < 0.05.
Figure 3

The expression levels of circRNAs in the replication samples. The expression levels of hsa-circ-0000267 (a), hsa-circ-0001173 (b), hsa-circ-0006758 (c), hsa-circ-0008285 (d), hsa-circ-0014879 (e), hsa-circ-0024604 (f), hsa-circ-0035796 (g), hsa-circ-0001811 (h), and hsa-circ-0084615 (i) were detected using qPCR assay. *P < 0.05.

3.5 Construction of the hsa-circ-0008285 gene interaction networks

To better understand the role of hsa-circ-0008285, we used computational tools to predict hsa-circ-0008285-interacting mRNAs, miRNAs, or other circRNAs. From the same sample as the circRNA chip, we carried out whole transcriptome detection of mRNA, micro-RNA as well as mRNA related to circ-0008285 as shown in Figure 4. There were a total of 117 miRNAs, 60 mRNA, and 39 circ-RNAs.

Figure 4 
                  A hsa-circ-0008285-derived gene network. hsa-circ-0008285 targeted mRNAs (n = 60, green circular), circRNAs (n = 39, blue circular), and miRNAs (n = 117, red circular) were predicted by bioinformatics, luciferase reporting system, CHIRP, and RNA sequencing.
Figure 4

A hsa-circ-0008285-derived gene network. hsa-circ-0008285 targeted mRNAs (n = 60, green circular), circRNAs (n = 39, blue circular), and miRNAs (n = 117, red circular) were predicted by bioinformatics, luciferase reporting system, CHIRP, and RNA sequencing.

4 Discussion

circRNAs are in low abundance but notably stable and widespread in human tissues and cells [29,30]. Recently, thousands of circRNAs have been identified in various tissues and organs, and most of the circRNAs were associated with many diseases [30,31,32,33,34].

In this study, we systematically analyzed shifts in the expression of 5,680 circRNAs in severe sepsis using high-throughput circRNA arrays. The analysis identified 760 differentially expressed circRNAs. The differentially expressed circRNAs suggested many novel biological processes or pathways that are involved in the pathophysiology of severe sepsis. We have, for the first time, systematically identified circRNAs on a genome-wide scale for severe sepsis. We identified hundreds of circRNAs that were differentially expressed in severe sepsis. According to the qPCR results, we validated circRNAs such as hsa-circ-0008285 (exons of CDYL) and hsa-circ-0001811 (exons of STAU2) as potential biomarkers for severe sepsis.

In recent studies, hsa-circ-0008285 has been shown to adsorb Let-7c and inhibit the entry of interferon regulatory factor 4 into the nucleus, thereby promoting the expression of C/EBP-δ, promoting vascular inflammation, and inducing M1 polarization in macrophages [35]. Although hsa-circ-0008285 has been confirmed to be involved in inflammation, its expression and role in severe sepsis have not been reported. In addition, hsa_circ_0001811 was low expressed in gastric cancer [36], and targeted the miR-589/CAPZA1 axis to inhibit the progression of gastric cancer [37]. However, most of the circRNAs are still less studied in severe sepsis. More comprehensive functional studies in the future are needed to validate their roles and molecular mechanisms in severe sepsis.

GO and pathway analysis studies showed that sepsis-related circRNAs were localized in exons of protein-coding genes. These circRNAs were enriched for genes involved in many metabolic processes or immune functions. These results supported the pathology of sepsis as a systemic inflammation in response to infection. circRNAs may interact with their hosting genes or miRNAs to regulate such processes or pathways.

However, this study only performed six high-throughput circRNA arrays. The small sample size reduced the confidence of the initial results defining the differentially expressed circRNAs. In addition, both the patients and control samples included in this study were male, which led to reduced reliability of the research results. We plan to conduct further follow-up validation studies for the top results to provide more reliable results.

Acknowledgment

The present study was supported by the Guangdong Provincial People’s Hospital.

  1. Funding information: This study was supported by the National Clinical Key Subject Construction Project (2012-649), Stability support for provincial scientific research institutions (KD032023004) and the Clinical Specialty Technology Construction Project of Guangzhou (2023P-TS19).

  2. Author contributions: L.J. analyzed the data and wrote manuscripts. W.G. was responsible for doing experiments and writing manuscripts. Z.W. and T.Q. assisted in the experiment. Z.W., S.W., and X.L. assisted in the analysis of experimental data. L.J., S.W., and X.L. revised the manuscript. All authors have read and agreed to the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

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

References

[1] Zhang YY, Ning BT. Signaling pathways and intervention therapies in sepsis. Signal Transduct Target Ther. 2021;6(1):407.Search in Google Scholar

[2] Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486–552.Search in Google Scholar

[3] Rhee C, Chiotos K, Cosgrove SE, Heil EL, Kadri SS, Kalil AC, et al. Infectious diseases society of america position paper: recommended revisions to the national severe sepsis and septic shock early management bundle (SEP-1) sepsis quality measure. Clin Infect Dis. 2021;72(4):541–52.Search in Google Scholar

[4] Jiang S, Ma J, Ye S, Meaney C, Moore TE, Pan S, et al. Associations among disseminated intravascular coagulation, thrombocytopenia cytokines/chemokines and genetic polymorphisms of toll-like receptor 2/4 in Chinese patients with sepsis. J Inflamm Res. 2022;15:1–15.Search in Google Scholar

[5] Djuric O, Andjelkovic M, Vreca M, Skakic A, Pavlovic S, Novakovic I, et al. Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA. Injury. 2021;52(3):419–25.Search in Google Scholar

[6] Mustarim M, Yanwirasti Y, Jamsari J, Rukmono R, Nindrea RD. Association of gene polymorphism of bactericidal permeability increasing protein Rs4358188, cluster of differentiation 14 Rs2569190, interleukin 1β Rs1143643 and matrix metalloproteinase-16 Rs2664349 with neonatal sepsis. Open Access Maced J Med Sci. 2019;7(17):2728–33.Search in Google Scholar

[7] Severino P, Silva E, Baggio-Zappia GL, Brunialti MKC, Nucci LA, Junior OR, et al. Gene expression profiling of mononuclear cells from patients with sepsis secondary to community-acquired pneumonia. Genomics Data. 2014;2:332–4.Search in Google Scholar

[8] Severino P, Silva E, Baggio-Zappia GL, Brunialti MKC, Nucci LA, Rigato Jr O, et al. Patterns of gene expression in peripheral blood mononuclear cells and outcomes from patients with sepsis secondary to community acquired pneumonia. PLoS One. 2014;9(3):e91886.Search in Google Scholar

[9] Zhang T-N, Da Li JX, Wu Q-J, Wen R, Yang N, Liu C-F. Non-coding RNA: a potential biomarker and therapeutic target for sepsis. Oncotarget. 2017;8(53):91765.Search in Google Scholar

[10] Liu CX, Chen LL. Circular RNAs: Characterization, cellular roles, and applications. Cell. 2022;185(12):2016–34.Search in Google Scholar

[11] Yang L, Wilusz JE, Chen LL. Biogenesis and regulatory roles of circular RNAs. Annu Rev Cell Dev Biol. 2022;38:263–89.Search in Google Scholar

[12] Chen LL. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol. 2020;21(8):475–90.Search in Google Scholar

[13] Hsu M-T, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280(5720):339.Search in Google Scholar

[14] Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE, et al. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 6(12):e1001233.Search in Google Scholar

[15] Ghosal S, Das S, Sen R, Basak P, Chakrabarti J. Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits. Front Genet. 2013;4:68415.Search in Google Scholar

[16] Li F, Zhang L, Li W, Deng J, Zheng J, An M, et al. Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway. Oncotarget. 6(8):6001–13.Search in Google Scholar

[17] Nair AA, Niu N, Tang X, Thompson KJ, Wang L. Circular RNAs and their associations with breast cancer subtypes. Oncotarget. 2016;7(49):80967.Search in Google Scholar

[18] Qu S, Yang X, Li X, Wang J, Li H. Circular RNA: a new star of noncoding RNAs. Cancer Lett. 2015;365(2):141–8.Search in Google Scholar

[19] Ng WL, Marinov GK, Liau ES, Lam YL, Lim Y-Y, Ea C-K. Inducible RasGEF1B circular RNA is a positive regulator of ICAM-1 in the TLR4/LPS pathway. RNA Biol. 2016;13(9):861–71.Search in Google Scholar

[20] Qi L, Yan Y, Chen B, Cao J, Liang G, Xu P, et al. Research progress of circRNA as a biomarker of sepsis: a narrative review. Ann Transl Med. 2021;9(8):720.Search in Google Scholar

[21] Yang D, Zhao D, Ji J, Wang C, Liu N, Bao X, et al. CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression. Front Immunol. 2023;14:1095457.Search in Google Scholar

[22] Niu F, Liang X, Ni J, Xia Z, Jiang L, Wang H, et al. CircRNA circFADS2 is under-expressed in sepsis and protects lung cells from LPS-induced apoptosis by downregulating miR-133a. J Inflamm (Lond). 2022;19(1):4.Search in Google Scholar

[23] Tian C, Liu J, Di X, Cong S, Zhao M, Wang K. Exosomal hsa_circRNA_104484 and hsa_circRNA_104670 may serve as potential novel biomarkers and therapeutic targets for sepsis. Sci Rep. 2021;11(1):14141.Search in Google Scholar

[24] Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol). 1995;57(1):289–300.Search in Google Scholar

[25] Rokach L, Maimon O. Clustering methods. Data mining and knowledge discovery. 2005. p. 321–52.Search in Google Scholar

[26] Alexa A, Rahnenfuhrer J. topGO: enrichment analysis for gene ontology. R package version. 2010;2- bioconductor.uib.no.Search in Google Scholar

[27] Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25(1):25.Search in Google Scholar

[28] Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30.Search in Google Scholar

[29] Bejugam PR, Das A, Panda AC. Seeing is believing: Visualizing circular RNAs. Noncoding RNA. 2020;6(4):45.Search in Google Scholar

[30] Verduci L, Tarcitano E, Strano S, Yarden Y, Blandino G. CircRNAs: role in human diseases and potential use as biomarkers. Cell Death Dis. 2021;12(5):468.Search in Google Scholar

[31] Wei L, Liu L, Bai M, Ning X, Sun S. CircRNAs: versatile players and new targets in organ fibrosis. Cell Commun Signal. 2023;21(1):90.Search in Google Scholar

[32] Li J, Sun C, Cui H, Sun J, Zhou P. Role of circRNAs in neurodevelopment and neurodegenerative diseases. J Mol Neurosci. 2021;71(9):1743–51.Search in Google Scholar

[33] Mo Y, Liu Y, Lu A, Zhang H, Tang L. Role of circRNAs in viral infection and their significance for diagnosis and treatment (Review). Int J Mol Med. 2021;47(5):88.Search in Google Scholar

[34] Guo X, Tan W, Wang C. The emerging roles of exosomal circRNAs in diseases. Clin Transl Oncol. 2021;23(6):1020–33.Search in Google Scholar

[35] Song H, Yang Y, Sun Y, Wei G, Zheng H, Chen Y, et al. Circular RNA Cdyl promotes abdominal aortic aneurysm formation by inducing M1 macrophage polarization and M1-type inflammation. Mol Ther. 2022;30(2):915–31.Search in Google Scholar

[36] Zhang H, Li Z, Ruan Y, Sun W, Yu R. Low expression of hsa_circ_0001811 in gastric cancer and its role in clinical diagnosis. J Clin Lab Anal. 2021;35(2):e23642.Search in Google Scholar

[37] Zhang C, Wei G, Zhu X, Chen X, Ma X, Hu P, et al. Exosome-delivered circSTAU2 inhibits the progression of gastric cancer by targeting the miR-589/CAPZA1 axis. Int J Nanomed. 2023;18:127–42.Search in Google Scholar

Received: 2023-10-18
Revised: 2024-06-03
Accepted: 2024-06-03
Published Online: 2024-07-24

© 2024 the author(s), published by De Gruyter

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

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
Downloaded on 27.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0900/html
Scroll to top button