Hereditas最新文献

{"title":"A pathogenic NR2F1 gene variant disrupts transcriptional activity and causes severe neurodevelopmental delay in Bosch-Boonstra-Schaaf syndrome.","authors":"Juan Liu, Jihong Hu, Pingqiu Zhou, Yaqin Duan, Shuigui Yin","doi":"10.1186/s41065-025-00394-8","DOIUrl":"10.1186/s41065-025-00394-8","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear receptor subfamily 2, group F, member 1 (NR2F1) gene variations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome. The NR2F1 genotype correlates with its phenotype; variants within the DNA-binding domain may cause severe psychomotor developmental disorders. However, the mechanisms underlying these phenotypes remain unclear.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed on the proband and her parents DNA. Candidate variants were verified by Sanger sequencing and bioinformatics analyses. Molecular dynamics simulations were performed to predict structural changes in the mutant NR2F1 protein. A dual-luciferase assay was used to analyze the variant's effect on transcriptional activation.</p><p><strong>Results: </strong>The proband was a 10-month-old girl with severe motor and cognitive developmental delays accompanied by bilateral optic nerve pallor. Genetic testing revealed a novel NR2F1 gene variant, NM_005654.6: c.452T > A (p.Met151Lys). Bioinformatics analysis suggested that this variant alters the protein structure or function. The molecular dynamics analysis showed that this variant might affect the stability of the zinc finger structure within the NR2F1 DNA-binding domain. Dual-luciferase assays indicated this variant affects transcriptional activation.</p><p><strong>Conclusions: </strong>The NR2F1 variant c.452T > A (p.Met151Lys) may genetically cause the severe clinical phenotypes observed in this patient. This finding expands the spectrum of NR2F1 variants.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"30"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIN1 inhibited tumor growth, metastasis and stemness by ALDH1/NOTCH pathway in bladder carcinoma.","authors":"Si-Yu Chen, Ya-Long Zhang, Xiao-Ran Li, Ji-Rong Wang, Kun-Peng Li, Shun Wan, Jian-Wei Yang, Hao Wang, Jin-Long Cao, Chen-Yang Wang, Xin-Peng Fan, Sheng-Jun Fu, Li-Yun Ding, Tuan-Jie Che, Li Yang","doi":"10.1186/s41065-025-00384-w","DOIUrl":"10.1186/s41065-025-00384-w","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BLCA) represents one of the most prevalent urological malignancies worldwide. Bridging integrator 1 (BIN1), a well-characterized tumor suppressor that interacts with and inhibits oncogenic Myc transcription factors, has demonstrated crucial roles in various cancer types. However, its specific functions and underlying molecular mechanisms in BLCA development and progression remain poorly understood. This study aims to elucidate the role of BIN1 in regulating BLCA cell proliferation, metastasis, and cancer stem cell properties.</p><p><strong>Methods: </strong>Using urinary proteomics analysis, we identified BIN1 as a significantly dysregulated protein in BLCA. The clinical significance of BIN1 was further validated through comprehensive analyses of public databases. BIN1 expression levels defined distinct molecular and immunological subtypes of BLCA. Through proteomic profiling of BIN1-overexpressing UMUC3 cells and corresponding controls, we identified ALDH1 as a key downstream effector in the BIN1-regulated ALDH1/NOTCH signaling axis. We employed multiple experimental approaches, including Western blot analysis, quantitative RT-PCR, immunofluorescence staining, wound healing assays, transwell migration assays, colony formation assays, tumor sphere formation assays, flow cytometry, CCK8 proliferation assays, and cell transfection experiments.</p><p><strong>Results: </strong>We observed significant downregulation of BIN1 in both BLCA tissues and cell lines compared to normal adjacent tissues and SV-HUC-1 cells, respectively. BIN1 overexpression inhibited cancer cell proliferation by promoting apoptosis and suppressed epithelial-mesenchymal transition (EMT), thereby reducing local invasion and distant metastasis. Additionally, BIN1 regulated cancer stem cell properties through modulation of ALDH1 expression, with NOTCH2 acting as a crucial downstream mediator of ALDH1 signaling.</p><p><strong>Conclusion: </strong>Our findings demonstrate that BIN1 functions as a tumor suppressor in BLCA and suggest its potential utility as both a diagnostic biomarker and therapeutic target for BLCA treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"29"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the association between rheumatoid arthritis and non-small cell lung cancer risk: a transcriptomic and drug target-based analysis.","authors":"Lyubo Wang, Yuxian Dong, Qingcheng Yang, Siyun Liu, Bencheng Wu, Dahang Zhang, Shuai Shen, Chenjun Xin, Zurui Liu, Qiuyang Wu, Guojian Huang, Lincan Duan","doi":"10.1186/s41065-025-00396-6","DOIUrl":"10.1186/s41065-025-00396-6","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) is a common subtype of lung cancer that has received considerable attention for its potential association with rheumatoid arthritis (RA). However, current understanding of the relationship between RA and NSCLC risk remains limited and in-depth studies of molecular mechanisms are lacking.</p><p><strong>Methods: </strong>We obtained transcriptomic data of NSCLC from the Gene Expression Omnibus (GEO) database and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differential genes. We then used Mendelian randomisation (MR) analysis to explore the causal relationship between RA and NSCLC, but the results showed no direct causal relationship between RA and NSCLC. In light of this finding, we shifted our research focus to investigate the effect of RA therapeutics on NSCLC risk. A drug-targeted MR analysis of drugs available for the treatment of RA was performed by searching for drugs that target NSCLC differential genes associated with RA.</p><p><strong>Results: </strong>We found that several of the drugs corresponding to NSCLC differential genes associated with RA are used to treat RA. By drug-targeted MR analysis of drugs, we found that some drugs do have an effect on the risk of developing NSCLC, increasing the risk of developing NSCLC.</p><p><strong>Conclusion: </strong>This study employed transcriptomic analysis and MR of drug targets to elucidate the potential correlation between RA and the risk of developing NSCLC. The identification of NSCLC differentially expressed genes associated with RA and their drug targets has provided new perspectives for an in-depth understanding of the pathogenesis of NSCLC. Furthermore, an additional immune infiltration analysis demonstrated that, in NSCLC tissues, the infiltration levels of specific immune cell subpopulations, including regulatory T cells (Tregs), activated natural killer cells (NK cells) and unpolarised macrophages (M0), exhibited notable differences. These findings emphasise the significant role that immune cell interactions between RA and NSCLC may play in disease progression. Furthermore, through the analysis of validation histology, we have further confirmed the potential role of differential genes associated with RA in the development of NSCLC. The expression levels of these genes demonstrated significant differences in NSCLC samples, providing a basis for possible future therapeutic targets and biomarkers.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"28"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of subtypes and biomarkers associated with disulfidptosis-related ferroptosis in ulcerative colitis.","authors":"Yinghao Jiang, Hongyan Meng, Xin Zhang, Jinguang Yang, Chengxin Sun, Xiaoyan Wang","doi":"10.1186/s41065-025-00390-y","DOIUrl":"10.1186/s41065-025-00390-y","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis and ferroptosis are different programmed cell death modes, which are closely related to the development of a variety of diseases, but the relationship between them and ulcerative colitis (UC) is still unclear. Therefore, our study aimed to explore the molecular subtypes and biomarkers associated with disulfidptosis-related ferroptosis (DRF) in UC.</p><p><strong>Methods: </strong>We used Pearson analysis to identify DRF genes. Then, we classified 140 UC samples into different subtypes based on the DRF genes and explored the biological and clinical characteristics between them. Next, the hub genes were identified by differential analysis and WGCNA algorithms, and three machine learning algorithms were used to screen biomarkers for UC from hub genes. In addition, we analyzed the relationship between biomarkers of immune cells and transcription factors and predicted natural compounds that might be used to treat UC. Finally, we further verified the reliability of the markers by RT-qPCR experiments.</p><p><strong>Results: </strong>118 DRF genes were identified using Pearson analysis. Based on the expression level of the DRF genes, we classified UC patients into C1 and C2 subtypes, with significant differences in the abundance of immune infiltration and disease activity between the two subtypes. The machine learning algorithms identified three biomarkers, including XBP1, FH, and MAP3K5. Further analyses revealed that the three biomarkers were closely associated with a variety of immune cells and transcription factors. In addition, six natural compounds corresponding to the biomarkers were predicted, which may contribute to the effective treatment of UC. Finally, the expression trends of XBP1, FH, and MAP3K5 in animal experiments were consistent with the results of bioinformatics analysis.</p><p><strong>Conclusion: </strong>In this study, we systematically elucidated the role of DRF genes in the development of UC, and identified three potential biomarkers, providing a new idea for the diagnosis and treatment of UC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"27"},"PeriodicalIF":2.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfidptosis classification of pancreatic carcinoma reveals correlation with clinical prognosis and immune profile.","authors":"Jiangmin Shi, Liang Zhao, Kai Wang, Jieqiong Lin, Jianwei Shen","doi":"10.1186/s41065-025-00381-z","DOIUrl":"10.1186/s41065-025-00381-z","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis, a novel form of metabolism-related regulated cell death, is a promising intervention for cancer therapeutic intervention. Although aberrant expression of long-chain noncoding RNAs (lncRNAs) expression has been associated with pancreatic carcinoma (PC) development, the biological properties and prognostic potential of disulfidptosis-related lncRNAs (DRLs) remain unclear.</p><p><strong>Methods: </strong>We obtained RNA-seq data, clinical data, and genomic mutations of PC from the TCGA database, and then determined DRLs. We developed a risk score model and analyzed the role of risk score in the predictive ability, immune cell infiltration, immunotherapy response, and drug sensitivity.</p><p><strong>Results: </strong>We finally established a prognostic model including three DRLs (AP005233.2, FAM83A-AS1, and TRAF3IP2-AS1). According to Kaplan-Meier curve analysis, the survival time of patients in the low-risk group was significantly longer than that in the high-risk group. Based on enrichment analysis, significant associations between metabolic processes and differentially expressed genes were assessed in two risk groups. In addition, we observed significant differences in the tumor immune microenvironment landscape. Tumor Immune Dysfunction and Rejection (TIDE) analysis showed no statistically significant likelihood of immune evasion in both risk groups. Patients exhibiting both high risk and high tumor mutation burden (TMB) had the poorest survival times, while those falling into the low risk and low TMB categories showed the best prognosis. Moreover, the risk group identified by the 3-DRLs profile showed significant drug sensitivity.</p><p><strong>Conclusions: </strong>Our proposed 3-DRLs-based feature could serve as a promising tool for predicting the prognosis, immune landscape, and treatment response of PC patients, thus facilitating optimal clinical decision-making.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"26"},"PeriodicalIF":2.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The causal relationships between gut microbiota and venous thromboembolism: a Mendelian randomization study.","authors":"Pin Huang, Ying Xiao, Ye He","doi":"10.1186/s41065-025-00389-5","DOIUrl":"10.1186/s41065-025-00389-5","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is still one of the most severe health issues, increasing mortality and lengthening hospital stays. Different abundances of gut microbiota have been clinically linked to VTE and coagulopathy. However, whether gut microbiota affected VTE formation remained uncertain.</p><p><strong>Methods: </strong>The causative links between VTE and 211 gut microbiota at phylum, class, order, family and genus level were separately investigated using two-sample Mendelian Randomization (MR) analysis. Firstly, single nucleotide polymorphisms (SNPs) locus-wide significantly (P < 1.0 × 10^- 5) related with gut microbiome abundance were extracted from large genome-wide analysis (GWAS) meta-analysis summary data. Instrumental variables (IVs) without pleiotropy were selected using the PhenoScanner and MR PRESSO test. Then, the MR analysis was implemented using the inverse variance weighted (IVW) method. Moreover, weighted median method, MR Egger method, simple median method and MR PRESSO were conducted to validate the causal associations. The reliability of the results was also assessed utilizing various sensitivity analyses, reverse MR analysis and multivariate Mendelian Randomization analysis (MVMR).</p><p><strong>Results: </strong>We found the phylum Firmicutes was robustly protective against VTE with MR analysis. Moreover, five taxa of Actinobacteria phylum (Bifidobacteriales order, Actinomycetales order, Bifidobacteriaceae family, Actinomycetaceae family, Slackia genus) and two taxa of Firmicutes phylum (Bacillales order, Lachnospiraceae UCG-010 genus) were suggestively protective for VTE. While three taxa of Firmicutes phylum (Bacilli class, Lactobacillales order and Lactococcus genus) might suggestively increase the risk of VTE. Sensitivity analyses indicated no significant horizontal pleiotropy, heterogeneity, or reverse causal associations. Furthermore, MVMR analysis unveiled independently positive causal association of Firmicutes phylum and Lachnospiraceae UCG-010 genus with risk of VTE.</p><p><strong>Conclusion: </strong>Two taxa of gut microbes (Firmicutes phylum and Lachnospiraceae UCG-010 genus) were independently protective against VTE, which suggests a potential avenue for developing new cost-effective strategies with minor side effects for VTE prevention and treatment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"25"},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of biomarkers and mechanism exploration of ferroptosis related genes regulated by m6A in type 2 diabetes mellitus.","authors":"Jing Wang, Xuying Li, Juan Geng, Ruiduo Wang, Gang Ma, Pan Liu","doi":"10.1186/s41065-025-00385-9","DOIUrl":"10.1186/s41065-025-00385-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study is aims to explore the role of ferroptosis genes regulated by N6-methyladenosine (m6A) in Type 2 diabetes mellitus (T2DM).</p><p><strong>Material and methods: </strong>Firstly, differentially expressed m6A-FRGs (DEm6A-FRGs) were obtained by intersecting the differentially expressed genes (DEGs) and the m6A-related ferroptosis genes (m6A-FRGs). After enrichment analysis of DEm6A-FRGs, artificial neural network (ANN) and nomogram models were constructed using 4 biomarkers. Moreover, the gene set enrichment analysis of biomarkers was performed. Furthermore, the transcription factors (TF)-mRNA and competing endogenous RNAs (ceRNA) regulatory networks were constructed to reveal the potential regulation of biomarkers at molecular level. In addition, the targeted drugs of biomarkers were predicted, and the molecular docking was used to study the inter-molecular interactions between biomarkers and targeted drugs by \"AutoDockvina\".</p><p><strong>Results: </strong>Totals of 10 DEm6A-FRGs were obtained by intersecting the 402 DEGs and 299 m6A-FRGs. Moreover, the ANN model and nomogram model were constructed with 4 biomarkers including CDKN1A, MIOX, MYCN and CD82, among them, CDKN1A was the most important biomarker for forecasting T2DM. Notably, the function of extracellular matrix structural constituent was low expression in CD82 and MIOX, the function of mitochondrial protein-containing complex was high expression in CD82 and CDKN1A. Furthermore, TP63 could regulate CD82, CDKN1A and MIOX, GATA3 could regulate CD82, CDKN1A and MYCN at the same time. The ceRNA network was constructed with 4 mRNAs, 51 miRNAs and 37 lncRNAs, among them, XIST was a key lncRNA that associated with 12 miRNAs, which could influence CDKN1A. In addition, bisphenol A was associated with CD82 and MYCN, CGP 25608 was associated with CDKN1A and MIOX.</p><p><strong>Conclusion: </strong>This study revealed the potential molecular mechanisms of m6A-related ferroptosis genes in T2DM, which could provide novel insights for the clinical diagnosis and treatment of T2DM.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"24"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SREBF1, a target gene of multiple sclerosis and coronary heart disease: based on mendelian randomization study.","authors":"Linqin Du, Yangyang Cui, Yang Zhou, Ofe Eugene Kwaku, Xuefeng Ding, Lang Zeng, Shikang Li, Lijuan Xiong, Yonghong Zhang, Peng Zhou, Kun Wang, Rongchuan Yue","doi":"10.1186/s41065-025-00388-6","DOIUrl":"10.1186/s41065-025-00388-6","url":null,"abstract":"<p><strong>Background and purpose: </strong>Research shows that people with multiple sclerosis (MS) are more likely to experience cardiovascular complications. However, the precise mechanisms underlying this association remain unclear. This study investigated the causal relationship between MS and coronary heart disease (CHD) using Mendelian randomization (MR) techniques to clarify direct effects and identify relevant target genes.</p><p><strong>Methods: </strong>We conducted various methods, including two-sample MR. method, reverse, and multivariable MR analyses, to examine the causal relationship between MS and CHD. These. methodologies effectively mitigate confounding variables and neutralize adverse causal effects. Additionally, the study explored the involvement of social factors through a two-step MR analysis. The research team performed a thorough screening of differentially expressed genes in MS based on GEO database, identifying potential target genes that may be associated with genetic risk of CHD. Enrichment analyses and protein-protein interaction studies were used to elucidate biological functions associated with these genes. We included colocalization analysis and summary data-based Mendelian randomization (SMR) method for further screening of core genes to obtain target genes.Finally, we investigated how these genes might affect health by conducting a phenome-wide MR analysis.</p><p><strong>Results: </strong>Our findings revealed that genetic predisposition to MS significantly increases the risk of CHD, with an IVW-MR analysis yielding an odds ratio of 1.091 (95% CI: 1.030, 1.155, P = 0.0029). Mediation analysis revealed that frailty mediated 20.2% of the effect of MS on CHD (P = 0.026), suggesting that frailty is a critical pathway in this relationship. Additionally, low-density lipoprotein (LDL) is associated with an increased risk of developing both MS and CHD. We identified 3025 differentially expressed genes and 130 genes causally linked to CHD. Protein-protein interaction network analysis identified 77 interacting genes, with core genes such as SREBF1 involved in organelle regulation and nucleic acid metabolism. Colocalization analysis further supported the presence of shared genetic variants between IL6R and SREBF1 associated with CHD, with posterior probabilities (PPH4) of 90.2% and 92.3%, respectively. Interestingly, summary mendelian randomization (SMR) analysis revealed that SREBF1 may be a target gene for MS(bSMR=-0.174,PSMR = 0.0218, PHEIDI = 0.2806, topSNP: rs12951376). Further analysis of the phenome-wide MR did not find significant evidence of side effect associated with targeted therapy against SREBF1.</p><p><strong>Conclusion: </strong>This study provided genetic evidence indicating that indivduals with MS face higher risk of coronary heart disease. Furthermore, SREBF1 maybe a critical target gene which would significantly contribute to drug development.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"22"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the shared genetic structure between rheumatoid arthritis and stroke.","authors":"Qian Qin, Yong'An Jiang, Hengyi Fan, Raorao Yuan, Bo Zhong, Yichen Zhang, Zile Zhang, Xin Lei, Jianhui Cai, Shiqi Cheng","doi":"10.1186/s41065-025-00386-8","DOIUrl":"10.1186/s41065-025-00386-8","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) increases the risk of stroke. However, the relationship between RA and stroke remains unclear. This study aimed to explore the shared genetics architecture (i.e., common genetic basis between different traits, diseases, or phenotypes) of RA and stroke, aiming to improve the intervention and management of patients with RA and stroke.</p><p><strong>Methods: </strong>Pooled statistics from publicly available genome-wide association studies for RA (8,255 cases and 409,001 controls) and stroke (43,132 cases and 43,132 controls) were used. A genome-wide positive association was conducted to (examine the comprehensive effects of genetic variants on a particular trait, disease, or phenotype at the genome-wide scale). Local genetic correlation studies used linkage disequilibrium score regression and super genetic covariance analyzer. Single nucleotide polymorphisms (SNPs) at risk were identified using genome-wide association study multiple trait analysis and PLINK software (P_snp <5e-08), followed by functional localization and annotation using Functional Mapping and Annotation of Genome-Wide Association Studies to identify specific genes and genetic variants that may contribute to the disease. Finally, a transcriptome-wide association study explored the relationship between genes and their association with RA risk.</p><p><strong>Results: </strong>A genome-wide significant positive correlation was evident between RA and stroke (genetic correlation = 0.3756). Among the localized genomic regions, the correlation between RA and stroke in the region of chr2:201572564-202,829,668 was the most significant (p = 0.0015). We identified 179 significant SNPs and five common risk genes for RA and stroke (IRF5, RNASET2, ZNF438, UBE2LS, and SYNGR1). These genes are involved in the immune-inflammatory pathway.</p><p><strong>Conclusions: </strong>The findings suggest a shared genetic structure between RA and stroke. These findings may provide new insights into RA and stroke pathogenesis, and contribute to the development of new diagnostic markers and therapeutic targeted drugs to improve the clinical outcomes of patients with RA and stroke.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"23"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of endoplasmic reticulum stress and mitochondrial dysfunction related biomarkers in osteoporosis.","authors":"Yuxi Chen, Ke Bi, Chunzhi Zhang, Jiaao Gu, Zhange Yu, Jianping Lu, Lei Yu","doi":"10.1186/s41065-025-00387-7","DOIUrl":"10.1186/s41065-025-00387-7","url":null,"abstract":"<p><strong>Background: </strong>Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction (MD) involved in bone metabolism disorders. However, the particular mechanisms of ERS and MD related genes (ERS&MDRGs) in osteoporosis (OP) have not been elucidated. In present study, biomarkers related to ERS and MD in OP were identified.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were obtained based on GEO dataset. ERS&MDRGs were derived from Genecard database. Initially, ERS&MD related DEGs (ERS&MDRDEGs) were obtained by overlapping DEGs and ERS&MDRGs. The key module was screened by WGCNA. The intersection of ERS&MDRDEGs and key module was screened by machine learning to obtain key genes. Then, receiver operating characteristic curve (ROC) was drawn to calculated diagnostic accuracy of key genes. The ssGSEA and Cibersort algorithms were performed to analyze immune cell infiltration. The miRNA-mRNA-TF network were draw by cytoscape software. Moleculaer docking and DGIdb database were employed for screening potential drugs. Finally, the expression of key genes was verified by qRT-PCR.</p><p><strong>Results: </strong>The 122 ERS&MDRDEGs were obtained by preliminary screening. ERS&MDRDEGs were mainly enriched in lipid metabolism, calcium ion transport, and ossification. The 5 key genes were identified, including AAAS, ESR1, SLC12A2, TAF15, and VAMP2. Immune infiltration analysis showed monocyte and macrophage were different between OP and control groups. The miRNA-mRNA-TF regulatory network indicated has-miR-625-5p, has-miR-296-3p, CTCT and EP300 as potential regulatory targets. The 2 potential small molecule drugs, namely bumetanide and elacestrant were screened. The expression of AAAS, ESR1, VAMP2 were higher, and SLC12A2 and TAF15 were lower in OP than control group.</p><p><strong>Conclusion: </strong>This research identified 5 key genes AAAS, ESR1, SLC12A2, TAF15 and VAMP2. Bumetanide and elacestrant were potential drugs. These findings provided valuable insights into the pathophysiology of OP and the development of new therapeutic strategies.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"21"},"PeriodicalIF":2.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}