Hereditas最新文献

{"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":"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":"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":"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}

{"title":"Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study.","authors":"Chao Zhang, Tao Yang, Yuan Yu, Qian Jia, Wan-Meng Xiao, Sha Liu, Ze-Hui Yu, Cheng-Li Wen, Yan Wei, Hao Li, Mu-Han Lü","doi":"10.1186/s41065-025-00378-8","DOIUrl":"10.1186/s41065-025-00378-8","url":null,"abstract":"<p><strong>Background: </strong>Previous research has established a correlation between immune cells and an increased likelihood of Chronic pancreatitis (CP). However, studies investigating the causal relationship remain limited.</p><p><strong>Methods: </strong>This study utilized publicly available genome-wide association study (GWAS) databases and conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationships (CRs) among 731 immune cells, 1,400 metabolites, and CP. Mediation MR analysis was also performed to assess whether metabolites serve as mediators in the relationship between immune cells and CP.</p><p><strong>Results: </strong>Our study identified four immune cell types that act as risk factors for CP, with odds ratios (OR) ranging between 1.076 and 1.177. In contrast, three immune cell types were found to serve as protective factors, exhibiting OR values between 0.846 and 0.913. Additionally, four metabolites were implicated as risk factors for CP, with OR values ranging from 1.243 to 1.334. On the other hand, eight metabolites were discovered to have a protective effect, with OR values between 0.580 and 0.871. Mediation analysis revealed that cholesterol levels mediate the causal relationship between immune cell cells and CP, with a mediation effect of 0.00918, accounting for 9.18% of the total effect.</p><p><strong>Conclusions: </strong>Our findings provide valuable insights into the genetic underpinnings of CP, highlighting the role of immune cells and plasma metabolites in its pathogenesis. The mediation analysis further suggests that the presence of CD25 on IgD-CD38-B cells may facilitate CP development through the elevation of cholesterol levels. These results not only deepen our understanding of CP but also suggest potential biological targets for therapeutic intervention. Future clinical research should focus on these mediators to develop more effective treatment strategies for CP.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"20"},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407116","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":"CDCA genes as prognostic and therapeutic targets in Colon adenocarcinoma.","authors":"Zongquan Zhao, Xinwei Feng, Bo Chen, Yihong Wu, Xiaohong Wang, Zhenyuan Tang, Min Huang, Xiaohua Guo","doi":"10.1186/s41065-025-00368-w","DOIUrl":"10.1186/s41065-025-00368-w","url":null,"abstract":"<p><strong>Objectives: </strong>The study investigates the role of Cell Division Cycle Associated (CDCA) genes in colorectal cancer (COAD) by analyzing their differential expression, epigenetic alterations, prognostic significance, and functional associations.</p><p><strong>Methodology: </strong>This study employed a detailed in silico and in vitro experiments-based methodology.</p><p><strong>Results: </strong>RT-qPCR assays reveal significantly elevated mRNA levels of CDCA2, CDCA3, CDCA4, CDCA5, CDCA7, and CDCA8 genes in COAD cell lines compared to controls. Bisulfite sequencing indicates reduced promoter methylation of CDCA gene promoters in COAD cell lines, suggesting an epigenetic regulatory mechanism. Analysis of large TCGA datasets confirms increased CDCA gene expression in COAD tissues. Survival analysis using cSurvival database demonstrates negative correlations between CDCA gene expression and patient overall survival. Additionally, Lasso regression-based models of CDCA genes predict survival outcomes in COAD patients. Investigating immune modulation, CDCA gene expression inversely correlates with immune cell infiltration and immune modulators. miRNA-mRNA network analysis identifies regulatory miRNAs targeting CDCA genes, validated by RT-qPCR showing up-regulation of has-mir-10a-5p and has-mir-20a-5p in COAD cell lines and tissues. Drug sensitivity analysis suggests resistance to specific drugs in COAD patients with elevated CDCA gene expression. Furthermore, CDCA gene expression correlates with crucial functional states in COAD, including \"angiogenesis, apoptosis, differentiation, hypoxia, inflammation, and metastasis.\" Additional in vitro experiments revealed that CDCA2 and CDCA3 knockdown in SW480 and SW629 cells significantly reduced cell proliferation and colony formation while enhancing cell migration.</p><p><strong>Conclusion: </strong>Overall, the study elucidates the multifaceted role of CDCA genes in COAD progression, providing insights into potential diagnostic, prognostic, and therapeutic implications.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"19"},"PeriodicalIF":2.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382247","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 effects between low back pain and cerebrospinal fluid metabolites: a two-sample Mendelian randomization study.","authors":"Run Peng, Xiaoxin Wang, Wei Wang, Zeqin Li, Yuze Sun, Mingliang Yang","doi":"10.1186/s41065-025-00374-y","DOIUrl":"10.1186/s41065-025-00374-y","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have shown an association between cerebrospinal fluid (CSF) metabolites and low back pain (LBP), but the causal relationship between these factors remains unclear.</p><p><strong>Methods: </strong>We performed a two-sample Mendelian randomization (MR) analysis to examine whether there is a causal relationship between CSF metabolites and LBP. We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald ratio, and MR-PRESSO, to test the causal relationship and conducted a sensitivity analysis to assess the robustness of the results.</p><p><strong>Results: </strong>We identified a total of 12 CSF metabolites significantly associated with LBP, of which Bilirubin, 5,6-dihydrothymine, Erythronate, Mannitol/sorbitol, and Butyrate have a potential inhibitory causal effect on LBP risk (p < 0.05). Meanwhile, 2-hydroxyadipate, Gamma-glutamyl-alpha-lysine, Indoleacetate, N-acetylputrescine, Palmitoyl dihydrosphingomyelin, S-methylcysteine, and 2,3-dihydroxy-5-methylthio-4-pentenoate play a causal role in increasing the risk of LBP (p < 0.05). No significant estimates of heterogeneity or pleiotropy were detected.</p><p><strong>Conclusion: </strong>Our study emphasizes the causal relationship between CSF metabolites and LBP risk, providing reference for clinical treatment and prognosis of LBP.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"18"},"PeriodicalIF":2.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364549","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":"Multiple machine learning-based integrations of multi-omics data to identify molecular subtypes and construct a prognostic model for HNSCC.","authors":"Xiaoqin Luo, Chao Li, Gang Qin","doi":"10.1186/s41065-025-00380-0","DOIUrl":"10.1186/s41065-025-00380-0","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has introduced new breakthroughs in improving the survival of head and neck squamous cell carcinoma (HNSCC) patients, yet drug resistance remains a critical challenge. Developing personalized treatment strategies based on the molecular heterogeneity of HNSCC is essential to enhance therapeutic efficacy and prognosis.</p><p><strong>Methods: </strong>We integrated four HNSCC datasets (TCGA-HNSCC, GSE27020, GSE41613, and GSE65858) from TCGA and GEO databases. Using 10 multi-omics consensus clustering algorithms via the MOVICS package, we identified two molecular subtypes (CS1 and CS2) and validated their stability. A machine learning-driven prognostic signature was constructed by combining 101 algorithms, ultimately selecting 30 prognosis-related genes (PRGs) with the Elastic Net model. This signature was further linked to immune infiltration, functional pathways, and therapeutic sensitivity.</p><p><strong>Results: </strong>CS1 exhibited superior survival outcomes in both TCGA and META-HNSCC cohorts. The PRG-based signature stratified patients into low- and high-risk groups, with the low-risk group showing prolonged survival, enhanced immune cell infiltration (B cells, T cells, monocytes), and activated immune functions (cytolytic activity, T cell co-stimulation). High-risk patients were more sensitive to radiotherapy and chemotherapy (e.g., Cisplatin, 5-Fluorouracil), while low-risk patients responded better to immunotherapy and targeted therapies.</p><p><strong>Conclusion: </strong>Our study delineates two molecular subtypes of HNSCC and establishes a robust prognostic model using multi-omics data and machine learning. These findings provide a framework for personalized treatment selection, offering clinical insights to optimize therapeutic strategies for HNSCC patients.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"17"},"PeriodicalIF":2.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255593","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}