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bioinformatics analysis and experimental validation of potential targets and pathways in chronic kidney disease associated with renal fibrosis

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JOURNAL OF TRANSLATIONAL MEDICINE 2025年第1期23卷 1-18页

作者： Cui, Huimin Zhao, Yuxin Wang, Peng Gong, Wei Lin, Hong Li, Na Yang, Jianjun Ningxia Med Univ Sch Publ Hlth 1160 Shengli St Yinchuan 750004 Peoples R China Ningxia Key Lab Environm Factors & Chron Dis Contr Yinchuan 750004 Peoples R China Ningxia Med Univ Gen Hosp Emergency Ctr Yinchuan 750004 Peoples R China Ningxia Med Univ Sch Nursing Yinchuan 750004 Peoples R China

Background Chronic kidney disease (CKD) has emerged as a major health problem worldwide. Previous studies have shown that specific miRNA expression profiles of patients with CKD are significantly changed. In this study, we aim to elucidate the role of miRNAs as potential biomarkers in CKD progression by integrating bioinformatics analysis with experimental validation, thereby providing medical evidence for the prevention and treatment of CKD. Method bioinformatics analysis was used to identify potential targets and pathways in CKD-associated renal fibrosis through randomly obtaining miRNA microarray data related to CKD patients in the Gene Expression Omnibus (GEO) database according to the inclusion and exclusion criteria, conducting pathway enrichment analysis and constructing protein-protein interaction (PPI) networks and miRNA-mRNA network by Cytoscape 3.8.0. In vitro experiments were employed to verify the role and mechanism of miR-223-3p in human renal tubular epithelial cells (HK2) through Quantitative real-time PCR assays, Western blot, Immunofluorescence analysis and Double luciferase reporter gene experiment. Multi-group one-way analysis of variance (ANOVA) and the Dunnett-t test were uesd to analyze the results by SPSS24.0. Results 10 up-regulated and 11 down-regulated miRNAs of CKD patients were screened out. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was the first pathway of pathway enrichment analysis. MiR-223-3p (logFC=-2.047, p = 0.002) was one of the four hub miRNAs. Furthermore, we observed a reduction in alpha-smooth muscle actin (alpha-SMA) (p = 0.001) and Collagen type I alpha 1 (Col1-a1) (p = 0.023) levels upon miR-223-3p overexpression, which aligned with our bioinformatics predictions. This downregulation was attributed to the inhibition of nuclear factor kappa-B (NF-kappa B) nuclear translocation and subsequent decrease in the secretion of inflammatory cytokines, such as interleukin-6 (IL-6) (p = 0.005). Conversely, when CHUK w

关键词： Chronic kidney disease bioinformatics analysis miR-223-3p Epithelial-mesenchymal transition PI3K/Akt pathway

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bioinformatics analysis of miR-2861 and miR-5011-5p that function as potential tumor suppressors in colorectal carcinogenesis

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BMC MEDICAL GENOMICS 2025年第1期18卷 1-12页

作者： Aytekin, Alper Kadakal, Hikmet Mihcioglu, Deniz Gurer, Turkan Gaziantep Univ Fac Med Dept Gen Surg TR-27310 Gaziantep Turkiye Gaziantep Univ Fac Art & Sci Dept Biol TR-27310 Gaziantep Turkiye SANKO Univ Fac Hlth Sci Dept Nutr & Dietet TR-27090 Gaziantep Turkiye

BackgroundThe study aimed to was to investigate the relationship between miR-2861, miR-5011-5p, and colorectal *** the present study, it was isolated RNA from both the tumor and non-tumor tissue of a total of 80 CRC patients and after synthesizing the cDNA, it was performed qRT-PCR to determine the expression levels of miR-2861 and miR-5011-5p. In addition, it was predicted that dysregulated miRNAs targets, pathways and functional gene annotations that may be important in colorectal carcinogenesis using KEGG pathway and GO *** resulting data revealed that both expression levels of miR-2861 and miR-5011-5p were significantly decreased in tumor tissues compared with non-tumor tissues of CRC patients. The GO and KEGG pathway analysis showed that miR-2861 and miR-5011-5p may participate in multiple the biological process, cellular components, and molecular function subcategories such as mitotic cell cycle, regulation of small GTPase mediated signal transduction, cell death, and acid binding transcription factor activity. It was also revealed that target genes of miRNAs can be found in signaling pathways such as TGF-beta, Rap1, Ras, cAMP, Wnt, mTOR and, PI3K-Akt signaling *** findings imply that miR-2861 and miR-5011-5p might function as tumor suppressors in the development of CRC.

关键词： bioinformatics analysis Colorectal cancer microRNA microRNA expression RT-qPCR

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bioinformatics analysis to identify environmental endocrine chemicals that target endometriosis genes

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025年 295卷 118136页

作者： Du, Kaile Xiong, Haiwei Zhang, Xiangcheng Luo, Ruihang Zhou, Boxuan Nanchang Univ Affiliated Hosp 1 Clin Med Coll 1 Jiangxi Med CollDept Breast Dis CtrGen Surg Nanchang 330006 Peoples R China Nanchang Univ Affiliated Hosp 1 Clin Med Coll 1 Dept GynecolJiangxi Med Coll Nanchang 330006 Peoples R China Nanchang Univ Affiliated Hosp 1 Jiangxi Med Coll Postdoctoral Innovat Practice Base Nanchang 330006 Peoples R China Nanchang Univ Affiliated Hosp 1 Jiangxi Med Coll Key Lab Jiangxi Prov Transfus Med Nanchang 330006 Peoples R China

Endometriosis (EMS) significantly impacts women's health and is influenced by genetic factors and environmental endocrine-disrupting chemicals (EDCs), which interfere with hormonal balance. Using the Gene Expression Omnibus database, we identified differentially expressed genes and applied analytical methods, including WGCNA, GO, KEGG, and LASSO regression, to predict six key genes associated with EMS: ADAMS, IRAK3, NTRK3, PIK3CG, STK38, and TLR4. By integrating the Comparative Toxicogenomics Database and Endocrine Disruption Exchange Database, we identified 35 EDCs potentially linked to these genes. This study highlights the relationship between EMS and EDCs, offering insights into its pathogenesis and potential therapeutic targets for improved treatment.

关键词： bioinformatics analysis Endometriosis (EMS) Endocrine-disrupting chemicals (EDCs) Key gene prediction Pathogenesis prediction

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bioinformatics analysis of coronary microvascular dysfunction in rats based on single-cell RNA sequencing

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SCIENTIFIC REPORTS 2025年第1期15卷 1-13页

作者： Li, Hao Jia, Yiding Chen, Zelin Yang, Luqun Ni, Lin Cao, Yuchen Fan, Rong Yuan, Zitong Zhu, Kaiyi Zhang, Zhijun Zuo, Lin Wu, Ping Gao, Yuping Lin, Yuanyuan Linfen Cent Hosp Dept Cardiol Linfen 041000 Peoples R China Shanxi Med Univ Tongji Shanxi Hosp Shanxi Bethune Hosp Shanxi Acad Med SciHosp 3Dept Cardiol 99 Longcheng St Taiyuan 030032 Shanxi Peoples R China Shanxi Med Univ Dept Cardiol Hosp 1 Taiyuan 030012 Peoples R China Shanxi Med Univ Lab Cell Physiol Jinzhong 030600 Peoples R China

Coronary microvascular dysfunction serves as one of the etiological factors for ischemic heart disease and represents a novel therapeutic direction for coronary artery diseases;however, the research on its pathogenesis remains inconsistent. This study aims to explore the single-cell gene expression profiles in rats with coronary microvascular dysfunction using single-cell RNA sequencing, with a particular focus on the in-depth analysis of endothelial cell gene expression characteristics. By establishing a rat model of coronary microvascular dysfunction, we collected cardiac apical tissue to prepare single-cell suspensions and further analyzed them using bioinformatics methods. From a total of 55,419 cells, we identified 28 distinct cell clusters, with endothelial cells and fibroblasts being the predominant cell types. Compared to the NC group, the proportion of endothelial cells in the CMD group was significantly reduced, while the number of fibroblasts was significantly increased. Through further analysis of the endothelial cells, we classified them into normal phenotype endothelial cells, mesenchymal phenotype endothelial cells, proliferative phenotype endothelial cells, and lymphatic endothelial cells, with mesenchymal and proliferative endothelial cells originating from normal phenotype endothelial cells. Additionally, the CMD group exhibited an increase in immune cells, enhanced inflammatory response, and increased oxidative stress. These findings may provide novel potential therapeutic targets for the treatment of Coronary microvascular dysfunction.

关键词： Coronary microvascular dysfunction Single-cell RNA sequencing bioinformatics analysis Endothelial cells Endothelial-to-mesenchymal transition

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bioinformatics analysis of potential pathogenesis and risk genes of neuroinflammation-promoted brain injury in intracerebral hemorrhage

BRAIN HEMORRHAGES

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BRAIN HEMORRHAGES 2025年第1期6卷 1-13页

作者： Gareev, Ilgiz Beylerli, Ozal Musaev, Elmar Wang, Chunlei Pavlov, Valentin Bashkir State Med Univ Ufa 450008 Russia Sechenov First Moscow State Med Univ Moscow Russia Harbin Med Univ Affiliated Hosp 1 Dept Neurosurg Harbin Heilongjiang Peoples R China

Objective: Spontaneous (non-traumatic) intracerebral hemorrhage (ICH) is one of the major causes of global death. The purpose of our bioinformatics analysis was to detect viable pathophysiological targets and small-molecule drug candidates and to identify the precise secondary mechanisms of brain injury in ICH. Methods: The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH. Online analysis tool GEO2R and Drug Susceptibility Assessment Module within the ACBI Bioinformation tool was used for data differential expression analysis. TargetScan, miRDB, and RNA22 were used to investigate the miRNAs regulating the DEGs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). DAVID is used to perform GO function enrichment analysis and KEGG pathway analysis of candidate target genes. Enrichment analysis was performed for delving the molecular mechanism of DEGs, and protein-protein interaction (PPI) networks and microRNA (miRNA)-messenger RNA (mRNA) networks were used to reveal the hub nodes and the related interaction relationships. Hub genes and miRNA-mRNA interaction of PPI network were identified by STRING version 12.0 online software and Cytoscape. Next, the DEGs were analyzed using the L1000CDS2 database to identify small-molecule compounds with potential therapeutic effects. Results: A total of 325 upregulated genes and 103 downregulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to cytokine-

关键词： Intracerebral hemorrhage bioinformatics analysis miRNA-mRNA network Neuroinflammation Signaling pathways Therapy Prognosis

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bioinformatics analysis of the Expression and Prognostic Significance of Transcription Factor YY1 in Gastric Cancer

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CANCER REPORTS 2025年第3期8卷 e70181页

作者： Chen, Wenliang Wang, Huanhuan Achi, Ntiak Hao, Jinjin Gong, Rui Zhao, Qiang Shanxi Med Univ Dept Gen Surg Affiliated Hosp 2 Taiyuan Shanxi Peoples R China Jincheng Peoples Hosp Dept Gen Surg Jincheng Shanxi Peoples R China Shanxi Med Univ Grad Dept Taiyuan Shanxi Peoples R China

Background: Emerging evidence indicates that the transcription factor Yin Yang 1 (YY1) plays a critical role in the carcinogenesis and progression of various human malignancies. YY1 is highly expressed in gastric cancer (GC), raising interest in its role in GC. Aims: This study aims to analyze the role of YY1 in gastric cancer, investigate its effect on the tumor microenvironment, and assess its potential as a prognostic marker. Methods and Results: Transcriptomic data and clinical information from GC patients were obtained from the TCGA and UCSC databases. YY1 expression was analyzed using the R "limma" package. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed with the online tool clusterProfiler. The relationship between YY1 expression levels and the tumor microenvironment was examined in different risk groups of GC patients. Additionally, YY1-positive staining in 26 clinical GC samples was measured using ImageJ software. Co-expression analysis was used to identify prognostic genes associated with YY1, and a prognostic risk model was built and optimized. Results showed that YY1 was significantly overexpressed in 415 GC (p < 0.001) and was associated with poorer survival outcomes (p = 0.043). GO and KEGG showed that YY1 was involved in key biological processes of the disease. Higher YY1 expression was correlated with lower stromal and immune cell content in the tumor microenvironment. Immunohistochemical staining confirmed YY1 overexpression in GC tissues compared to normal tissues (p = 0.0293). Positive correlations were observed between YY1 and the genes MTA1, TTL15, HNRNPU, WDR20, and PPP4R3A. The prognostic model, which included genes significantly associated with YY1 (risk score AUC = 0.690), predicted patient survival better than other clinical variables. Conclusion: These findings suggest that YY1 plays an important role in the development of GC. Targeting the YY1 pathway may be a potential trea

关键词： bioinformatics analysis gastric cancer immune cell infiltration Yin Yang 1

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Identification of Key Genes Mediated by N6-Methyladenosine Methyltransferase METTL3 in Ischemic Stroke via bioinformatics analysis and Experiments

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MOLECULAR BIOTECHNOLOGY 2025年第1期67卷 160-174页

作者： Liang, Tian Zhu, Lulu Yang, Jialei Huang, Xiaolan Lv, Miao Liu, Shengying Wen, Zheng Su, Li Zhou, Lifang Guangxi Med Univ Sch Publ Hlth 22 Shuangyong Rd Nanning 530021 Guangxi Peoples R China Liuzhou Ctr Dis Control & Prevent Liuzhou 545005 Guangxi Peoples R China

The N6-methyladenosine (m6A) methyltransferase METTL3 has been demonstrated to function in mediating m6A modification, but its role in ischemic stroke (IS) has not been fully elucidated. This study aimed to explore the downstream mechanism of METTL3-mediated m6A modification in IS. GSE16561 and GSE22255 were downloaded from the Gene Expression Omnibus database for analysis of differentially expressed genes (DEGs), and it was found that METTL3 mRNA was downregulated in IS. Then quantitative real-time polymerase chain reaction was used to verify the downregulation of METTL3 mRNA in the peripheral blood of IS patients and the cortexes of transient middle cerebral artery occlusion mice. By combining DEGs with the m6A-downregulated genes in GSE142386 which performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) on METTL3-deficient and control endothelial cells, a total of 131 genes were identified as the METTL3-mediated m6A-modified genes in IS. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the genes were mainly involved in cytokine-cytokine receptor interaction, MAPK signaling pathway and NF-kappa B signaling pathway. CTSS and SBK1 were further screened as the key METTL3-mediated m6A-modified genes by random forest model and PCR validation. The ROC curve analysis showed that the combination with CTSS and SBK1 was of good diagnostic value for IS, with the AUC of 0.810, sensitivity of 0.780, and specificity of 0.773. Overall, we found that METTL3-mediated m6A modification may influence the occurrence and development of IS by participating in inflammation-related biological processes, and two key m6A-modified genes mediated by METTL3 (CTSS and SBK1) can be used as diagnostic biomarkers for IS.

关键词： Ischemic stroke METTL3 bioinformatics analysis qRT-PCR

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Pesticide exposures and 10-year atherosclerotic cardiovascular disease risk: Integrated epidemiological and bioinformatics analysis

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JOURNAL OF HAZARDOUS MATERIALS 2025年 485卷 136835页

作者： Wu, Xueyan Wei, Dandan Zhou, Yilin Cao, Qingqing Han, Guozhen Han, Erbao Chen, Zhiwei Guo, Yao Huo, Wenqian Wang, Chongjian Huang, Shan Zeng, Xin Wang, Xinlu Mao, Zhenxing Zhengzhou Univ Coll Publ Hlth Dept Epidemiol & Biostat 100 Kexue Ave Zhengzhou 450001 Henan Peoples R China Zhengzhou Univ Coll Publ Hlth Dept Occupat & Environm Hlth Sci Zhengzhou Henan Peoples R China Henan Inst Food & Salt Ind Inspect Technol Zhengzhou Henan Peoples R China Zhengzhou Univ Sch Publ Hlth Zhengzhou Henan Peoples R China Collaborat Innovat Ctr Prevent & Treatment Major D Zhengzhou Henan Peoples R China

Background and purpose: Recent studies link pesticide exposures to cardiovascular disease risk factors. However, research on the combined effects of multiple pesticides on atherosclerotic cardiovascular disease (ASCVD) is limited, particularly in rural areas. Despite advances in toxicogenomics, the mechanisms underlying these effects remain unclear. This study aims to investigate the combined effects and mechanisms of pesticide exposures on ASCVD. Methods: In the cross-sectional study section, 2291 participants were included. Variables were filtered using machine learning models, and associations between mixed exposure to multiple pesticides and ASCVD were explored using environmental mixed exposure models (weighted quartile sum (WQS) regression and quantilebased g-computation (QGC)). In the bioinformatics analysis section, the GEO, CTD, Malacards, and GeneCards databases were used to retrieve target genes for pesticide exposure and atherosclerotic diseases. Enrichment analysis was then performed to identify the biological pathways associated with these genes. Results: Three machine models screened 34 pesticides. Single pesticide exposures, such as atrazine, oxadiazon, p, p '-DDE, alpha-BHC, beta-BHC, fenitrothion, malathion, fenitrothion, cypermethrin, cypermethrin, and cypermethrin might increase the 10-year ASCVD risk (all P < 0.05). Total mixed pesticide exposure was positively associated with 10-year ASCVD risk in both the QGC (3.223(2.196, 4.730)) and WQS models (4.642(3.070, 7.020)). Notably, there was a linear relationship between totalQGC (P_ overal < 0.001;P_ nonlinearity = 0.864) and high 10- year ASCVD risk. In toxicogenomic bioinformatics analysis, we identified 112 potential atherosclerosis target genes affected by pesticide exposure. Pathway enrichment analysis suggests pesticide-induced atherosclerosis is linked to pathways such as metabolic pathways, lipid metabolism, MAPK, AMPK, FoxO signaling, apoptosis, fluid shear stress, endocrine resistance, T

关键词： Pesticides, Mixed exposure 10-year ASCVD risk bioinformatics analysis Rural population

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Identification of high-risk non-synonymous SNPs (nsSNPs) in DNAH1 and DNAH17 genes associated with male infertility: a bioinformatics analysis

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JOURNAL OF APPLIED GENETICS 2025年第2期66卷 333-346页

作者： Navapour, Leila Mogharrab, Navid Parvin, Ali Arablouydareh, Sahar Rezaei Movahedpour, Ahmad Jebraeily, Mohamad Taheri-Anganeh, Mortaza Ghasemnejad-Berenji, Hojat Urmia Univ Med Sci Clin Res Inst Reprod Hlth Res Ctr Orumiyeh Iran Shiraz Univ Coll Sci Dept Biol Biophys & Computat Biol Lab BCBL Shiraz Iran Urmia Univ Med Sci Student Res Comm Orumiyeh Iran Mashhad Univ Med Sci Fac Med Dept Clin Biochem Mashhad Iran Behbahan Fac Med Sci Behbahan Iran Urmia Univ Med Sci Sch Allied Med Sci Dept Hlth Informat Technol Orumiyeh Iran Urmia Univ Med Sci Cellular & Mol Med Res Inst Cellular & Mol Res Ctr Orumiyeh Iran

Male infertility is a significant reproductive issue affecting a considerable number of couples worldwide. While there are various causes of male infertility, genetic factors play a crucial role in its development. We focused on identifying and analyzing the high-risk nsSNPs in DNAH1 and DNAH17 genes, which encode proteins involved in sperm motility. A total of 20 nsSNPs for DNAH1 and 10 nsSNPs for DNAH17 were analyzed using various bioinformatics tools including SIFT, PolyPhen-2, CADD, PhD-SNPg, VEST-4, and MutPred2. As a result, V1287G, L2071R, R2356W, R3169C, R3229C, E3284K, R4096L, R4133C, and A4174T in DNAH1 gene and C1803Y, C1829Y, R1903C, and L3595P in DNAH17 gene were identified as high-risk nsSNPs. These nsSNPs were predicted to decrease protein stability, and almost all were found in highly conserved amino acid positions. Additionally, 4 nsSNPs were observed to alter post-translational modification status. Furthermore, the interaction network analysis revealed that DNAH1 and DNAH17 interact with DNAH2, DNAH3, DNAH5, DNAH7, DNAH8, DNAI2, DNAL1, CFAP70, DNAI3, DNAI4, ODAD1, and DNAI7, demonstrating the importance of DNAH1 and DNAH17 proteins in the overall functioning of the sperm motility machinery. Taken together, these findings revealed the detrimental effects of identified high-risk nsSNPs on protein structure and function and highlighted their potential relevance to male infertility. Further studies are warranted to validate these findings and to elucidate the underlying mechanisms.

关键词： Male infertility DNAH1 DNAH17 nsSNPs bioinformatics analysis Sperm motility

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Machine learning-based characterization of PANoptosis-related biomarkers and immune infiltration in ulcerative colitis: A comprehensive bioinformatics analysis and experimental validation

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INTERNATIONAL IMMUNOPHARMACOLOGY 2025年 151卷 114298页

作者： Wan, Changshan Wu, Qiuyan Wang, Yali Sun, Yan Ji, Tao Gu, Yu Wang, Liwei Chen, Qiuyu Yang, Zhen Wang, Yao Wang, Bangmao Zhong, Weilong Tianjin Med Univ Gen Hosp Tianjin Inst Digest Dis Dept Gastroenterol & Hepatol Tianjin Key Lab Digest Dis Tianjin 300052 Peoples R China Tianjin Med Univ Gen Hosp Dept Obstet & Gynecol Tianjin 300052 Peoples R China Tianjin Univ Tradit Chinese Med Sch Integrat Med Tianjin 301617 Peoples R China Heilongjiang Univ Chinese Med Sch Basic Med Sci Harbin 150040 Peoples R China Linyi Peoples Hosp Dept Digest Gastroenterol & Hepatol Shandong 276000 Peoples R China Tianjin Med Univ Tianjin Cent Hosp 1 Dept Gastroenterol Tianjin 300192 Peoples R China Nankai Univ Tianjin Canc Inst Integrat Tradit Chinese & Wester Tianjin Union Med Ctr Dept Clin Lab Tianjin Peoples R China

Ulcerative colitis (UC) is a heterogeneous autoimmune condition. PANoptosis, a new form of programmed cell death, plays a role in inflammatory diseases. This study aimed to identify differentially expressed PANoptosisrelated genes (PRGs) involved in immune dysregulation in UC. Three key PRGs-BIRC3, MAGED1, and PSME2 were found using weighted gene co-expression network analysis (WGCNA) and machine learning. Immune infiltration analysis revealed that these key PRGs were associated with neutrophils, CD8+ T cells, activated CD4 T cells, and NK cells. Moreover, these key PRGs were significantly enriched in pathways related to inflammatory bowel disease, the IL-17 signaling pathway, and NOD-like receptor signaling pathway. The expression levels of the key PRGs were validated in various datasets, animal models, and UC intestinal tissue samples. Our findings confirmed the involvement of PANoptosis in UC and predict hub genes and immune characteristics, providing new insights for further investigations into UC pathogenic mechanisms and therapeutic strategies.

关键词： Ulcerative colitis PANoptosis bioinformatics analysis Machin learning Immune cell

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