Hereditas最新文献

{"title":"Hypermethylation of the sodium channel beta subunit gene promoter is associated with colorectal cancer.","authors":"Yabin Liu, Ya Duan, Tianliang Bai, Dexian Kong","doi":"10.1186/s41065-024-00340-0","DOIUrl":"https://doi.org/10.1186/s41065-024-00340-0","url":null,"abstract":"<p><strong>Aims: </strong>To better understand the role of sodium channel beta subunit (SCNN1B) in the initiation and progression of colorectal cancer (CRC) and to identify potential biomarkers for the early detection and prognosis of CRC.</p><p><strong>Methods: </strong>A total of 74 pairs of CRC tissues and their adjacent normal tissues were collected between October 2016 and November 2017. The methylation levels of the SCNN1B promoter region in CRC tissues and their adjacent normal tissues were investigated by pyrosequencing. The expression of both SCNN1B mRNA and protein were detected by RT‒qPCR and immunohistochemistry, respectively.</p><p><strong>Results: </strong>The results showed that the methylation levels of the SCNN1B promoter region were significantly higher in CRC tissues than in adjacent normal tissues. The expression levels of SCNN1B mRNA and protein were significantly lower in the CRC tissues than in their adjacent normal tissues. Moreover, Pearson's correlation analysis showed that the methylation levels of the SCNN1B promoter were negatively correlated with the SCNN1B mRNA levels in CRC tissues. In addition, the high methylation levels and low mRNA expression of SCNN1B showed a significant association with advanced tumour stage, increased risk of lymph node metastasis and poor prognosis of CRC patients.</p><p><strong>Conclusion: </strong>This study suggested that the decreased expression of SCNN1B due to its promoter hypermethylation may play an important role in the progression and prognosis of CRC, and the methylation levels of the SCNN1B promoter may serve as an effective molecular marker for predicting the progression and prognosis of CRC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463338","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":"Comprehensive analysis of a necroptosis-associated diagnostic signature for myelodysplastic syndromes based on single-cell RNA-seq and bulk RNA-seq.","authors":"Huimin Zhang, Li Zhang, Xiaoning Liang, Lihong Zhang, Bing Ma, Yuexian Li, Jianying Wang, Yang Shen, Yuhui Pang, Jianjun Xiong","doi":"10.1186/s41065-024-00335-x","DOIUrl":"https://doi.org/10.1186/s41065-024-00335-x","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndromes (MDS) are heterogeneous and clonal hematological disorders. The role and mechanism of necroptosis in MDS remain poorly understood.</p><p><strong>Methods: </strong>mRNA expression profiles and single-cell RNA-sequencing (scRNA-seq) data were sourced from the GEO database. ScRNA-seq data were processed using the \"Seurat\" package. After cell annotation, necroptosis-related scores (NRscores) for each cell were calculated using the \"UCell\" package. Differentially expressed genes (DEGs) and their associated biological functions in NRscore-related cell populations were identified. Additionally, DEGs and necroptosis-related genes (DE-NRGs) between MDS patients and healthy controls were identified. Consensus clustering was employed to classify MDS patients into distinct subclusters based on DE-NRGs. The biological functions and immune characteristics of these classifications were analyzed. Prognostic gene signatures were determined using LASSO and SVM-RFE analyses, and a nomogram was constructed based on the prognostic gene signature.</p><p><strong>Results: </strong>A total of 12 cell types were identified in MDS and healthy controls. NRscore was found to be elevated in monocytes and common lymphoid precursors (CLPs). Enrichment analysis revealed that monocytes and CLPs with high NRscore were associated with mitochondria-related and immune-related pathways. Eleven DEGs in monocytes and CLPs between MDS patients and healthy controls were identified. Additionally, 13 DE-NRGs were identified from 951 DEGs between MDS and healthy controls. MDS patients were classified into two distinct subclusters based on these 13 DE-NRGs, revealing several immune-related processes and signaling pathways. Differences in immune subpopulations between the two subclusters were observed. A necroptosis-related diagnostic gene signature (IRF9, PLA2G4A, MLKL, BAX, JAK2, and STAT3) was identified as predictive of MDS prevalence.</p><p><strong>Conclusion: </strong>Necroptosis plays a role in MDS progression by inducing inflammation. A novel necroptotic gene signature has been developed to distinguish and diagnose MDS at early stages of the disease.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463337","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 Jan Sjödin faba bean mutant collection: morphological and molecular characterization.","authors":"Hamid Khazaei, Ulrika Carlson-Nilsson, Alan H Schulman","doi":"10.1186/s41065-024-00339-7","DOIUrl":"https://doi.org/10.1186/s41065-024-00339-7","url":null,"abstract":"<p><strong>Background: </strong>Plant mutagenesis creates novel alleles, thereby increasing genetic and phenotypic diversity. The availability of the faba bean (Vicia faba L.) reference genome and a growing set of additional genomic resources has increased the scientific and practical value of mutant collections. We aimed to genotype and morphologically phenotype a historical faba bean mutant collection developed and characterized by Jan Sjödin (1934-2023) over half a century ago in order to increase its value to researchers. The collection was genotyped using high-throughput single-primer enrichment technology (SPET) assays.</p><p><strong>Results: </strong>We used 11,073 informative single nucleotide polymorphism (SNP) markers spanning the faba bean genome to genotype 52 mutant lines along with the background line, cv. Primus. A range of flower, seed, leaf, and stipule mutations were observed. The analysis of population structure revealed a shallow structure with no major subpopulations. Principal component and cluster analyses revealed, to a minor extent, that the mutants clustered by their phenotype.</p><p><strong>Conclusions: </strong>The mutants' phenotypic variation and shallow structure indicate that the Sjödin faba bean collection has the potential to play a significant role in faba bean breeding and in genetic and functional studies.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389856","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 necroptosis genes and characterization of immune infiltration in non-alcoholic steatohepatitis.","authors":"Huan Zhang, Yongqiang He, Yuqing Zhao, Malina Axinbai, Yuwei Hu, Shilei Liu, Jingmin Kong, Jinhui Sun, Liping Zhang","doi":"10.1186/s41065-024-00309-z","DOIUrl":"10.1186/s41065-024-00309-z","url":null,"abstract":"<p><strong>Background: </strong>The most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH.</p><p><strong>Methods: </strong>The GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT.</p><p><strong>Results: </strong>We identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9.</p><p><strong>Conclusions: </strong>We identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345170","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":"A novel approach for breast cancer treatment: the multifaceted antitumor effects of rMeV-Hu191.","authors":"Xiao-Yu Zheng, Yao Lv, Ling-Yan Xu, Dong-Ming Zhou, Lan Yu, Zheng-Yan Zhao","doi":"10.1186/s41065-024-00337-9","DOIUrl":"https://doi.org/10.1186/s41065-024-00337-9","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic potential of oncolytic measles virotherapy has been demonstrated across various malignancies. However, the effectiveness against human breast cancer (BC) and the underlying mechanisms of the recombinant measles virus vaccine strain Hu191 (rMeV-Hu191) remain unclear.</p><p><strong>Methods: </strong>We utilized a range of methods, including cell viability assay, Western blot, flow cytometry, immunofluorescence, SA-β-gal staining, reverse transcription quantitative real-time PCR, transcriptome sequencing, BC xenograft mouse models, and immunohistochemistry to evaluate the antitumor efficacy of rMeV-Hu191 against BC and elucidate the underlying mechanism. Additionally, we employed transcriptomics and gene set enrichment analysis to analyze the lipid metabolism status of BC cells following rMeV-Hu191 infection.</p><p><strong>Results: </strong>Our study revealed the multifaceted antitumor effects of rMeV-Hu191 against BC. rMeV-Hu191 induced apoptosis, inhibited proliferation, and promoted senescence in BC cells. Furthermore, rMeV-Hu191 was associated with changes in oxidative stress and lipid homeostasis in infected BC cells. In vivo, studies using a BC xenograft mouse model confirmed a significant reduction in tumor growth following local injection of rMeV-Hu191.</p><p><strong>Conclusions: </strong>The findings highlight the potential of rMeV-Hu191 as a promising treatment for BC and provide valuable insights into the mechanisms underlying its oncolytic effect.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345169","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":"Glutamine metabolism-related genes predict the prognostic risk of acute myeloid leukemia and stratify patients by subtype analysis","authors":"Jie Zhou, Na Zhang, Yan Zuo, Feng Xu, Lihua Cheng, Yuanyuan Fu, Fudong Yang, Min Shu, Mi Zhou, Wenting Zou, Shengming Zhang","doi":"10.1186/s41065-024-00338-8","DOIUrl":"https://doi.org/10.1186/s41065-024-00338-8","url":null,"abstract":"Acute myeloid leukemia (AML) is a genetically heterogeneous disease in which glutamine (Gln) contributes to AML progression. Therefore, this study aimed to identify potential prognostic biomarkers for AML based on Gln metabolism-related genes. Gln-related genes that were differentially expressed between Cancer Genome Atlas-based AML and normal samples were analyzed using the limma package. Univariate, least absolute shrinkage, selection operators, and stepwise Cox regression analyses were used to identify prognostic signatures. Risk score-based prognostic and nomogram models were constructed to predict the prognostic risk of AML. Subsequently, consistent cluster analysis was performed to stratify patients into different subtypes, and subtype-related module genes were screened using weighted gene co-expression network analysis. Through a series of regression analyses, HGF, ANGPTL3, MB, F2, CALR, EIF4EBP1, EPHX1, and PDHA1 were identified as potential prognostic biomarkers of AML. Prognostic and nomogram models constructed based on these genes could significantly differentiate between high- and low-risk AML with high predictive accuracy. The eight-signature also stratified patients with AML into two subtypes, among which Cluster 2 was prone to a high risk of AML prognosis. These two clusters exhibited different immune profiles. Of the subtype-related module genes, the HOXA and HOXB family genes may be genetic features of AML subtypes. Eight Gln metabolism-related genes were identified as potential biomarkers of AML to predict prognostic risk. The molecular subtypes clustered by these genes enabled prognostic risk stratification. ","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of N6-methyladenosine- and 5-methylcytosine-related long non-coding RNAs for predicting prognosis in cervical cancer","authors":"Jie Gao, Xiuling Zhang, Anqi Xu, Wei Li, HaiYan Gao","doi":"10.1186/s41065-024-00336-w","DOIUrl":"https://doi.org/10.1186/s41065-024-00336-w","url":null,"abstract":"N6-methyladenosine (m6A) and 5-methylcytosine (m5C) play a role in modifying long non-coding RNAs (lncRNAs) implicated in tumorigenesis and progression. This study was performed to evaluate prognostic value of m6A- and m5C-related lncRNAs and develop an efficient model for prognosis prediction in cervical cancer (CC). Using gene expression data of TCGA set, we identified m6A- and m5C-related lncRNAs. Consensus Clustering Analysis was performed for samples subtyping based on survival-related lncRNAs, followed by analyzing tumor infiltrating immune cells (TIICs). Optimal signature lncRNAs were obtained using lasso Cox regression analysis for constructing a prognostic model and a nomogram to predict prognosis. We built a co-expression network of 23 m6A-related genes, 15 m5C-related genes, and 62 lncRNAs. Based on 9 m6A- and m5C-related lncRNAs significantly associated with overall survival (OS) time, two molecular subtypes were obtained, which had significantly different OS time and fractions of TIICs. A prognostic model based on six m6A- and m5C-related signature lncRNAs was constructed, which could dichotomize patients into two risk subgroups with significantly different OS time. Prognostic power of the model was successfully validated in an independent dataset. We subsequently constructed a nomogram which could accurately predict survival probabilities. Drug sensitivity analysis found preferred chemotherapeutic agents for high and low-risk patients, respectively. Our study reveals that m6A- and m5C-related lncRNAs are associated with prognosis and immune microenvironment of CC. The m6A- and m5C-related six-lncRNA signature may be a useful tool for survival stratification in CC and open new avenues for individualized therapies.","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mir-150-5p distinguishes acute pulmonary embolism, predicts the occurrence of pulmonary arterial hypertension, and regulates ox-LDL-induced endothelial cell injury","authors":"Yue Wu, Xin Sun, Guangqiang Cui, Shu Wang","doi":"10.1186/s41065-024-00333-z","DOIUrl":"https://doi.org/10.1186/s41065-024-00333-z","url":null,"abstract":"Acute pulmonary embolism (APE) is a major type of venous thromboembolism (VTE) with a high risk of mortality and disability. There is a lack of biomarkers for APE to indicate deteriorating development and predict adverse outcomes. This study evaluated the significance of miR-150-5p in APE aiming to explore a novel potential biomarker for APE. The study enrolled APE (n = 137) and deep wein thrombosis (DVT, n = 67) patients and collected plasma samples from all study subjects. The expression of miR-150-5p was analyzed by PCR and its significance in screening APE and pulmonary arterial hypertension (PAH) was assessed by receiver operating curve (ROC) and logistic analyses. The study established oxidized low-density lipoprotein (ox-LDL)-induced human venous endothelial cells (HUVECs). Through cell transfection combined with cell counting kit-8 (CCK8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), the effect of miR-150-5p on ox-LDL-induced HUVEC injury was evaluated. Significant downregulation of miR-150-5p was observed in the plasma of APE patients compared with DVT patients (P < 0.0001). The plasma miR-150-5p levels in APE patients occurred PAH was much lower than in patients without PAH (P < 0.0001). Reducing miR-150-5p distinguished APE patients from DVT patients (AUC = 0.912) and was identified as a risk factor for the occurrence of PAH in APE patients (OR = 0.385, P = 0.010). In HUVECs, oxidized low-density lipoprotein (ox-LDL) caused inhibited cell proliferation, enhanced apoptosis, increased pro-inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and decreased superoxide dismutase (SOD). Overexpressing miR-150-5p could promote proliferation, inhibit apoptosis, and alleviate inflammation and oxidative stress of ox-LDL-treated HUVECs. Downregulated plasma miR-150-5p served as a diagnostic biomarker for APE and predicted the predisposition of PAH in APE patients. Overexpressing miR-150-5p could alleviate ox-LDL-induced endothelial cell injury in HUVECs.","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation.","authors":"Lin Xie, Hanze Liu, Ke Zhang, Yijun Pan, Mengyao Chen, Xiangyue Xue, Guoxing Wan","doi":"10.1186/s41065-024-00334-y","DOIUrl":"10.1186/s41065-024-00334-y","url":null,"abstract":"<p><strong>Background: </strong>Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations.</p><p><strong>Results: </strong>Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation.</p><p><strong>Conclusions: </strong>This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145561","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":"Can Omega-3 prevent the accidence of stroke: a mendelian randomization study.","authors":"Chongcheng Xi, Jie Zhang, Haihui Liu, Sian Tao, Ying Xie, Jibin Liu, Changqing Tong, Dong Tian, Hua Ye, Xiaobo Zhang","doi":"10.1186/s41065-024-00329-9","DOIUrl":"10.1186/s41065-024-00329-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms ","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132559","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}