{"title":"Investigation of lithium treatment during pregnancy on miR124 gene expression of offspring rats","authors":"Zeynab Askari , Parisa Hasanein , Alishir Haidari , Seyed Mohsen Saleh , Saeedeh Askarian","doi":"10.1016/j.humgen.2025.201429","DOIUrl":"10.1016/j.humgen.2025.201429","url":null,"abstract":"<div><div>Lithium, recognized as a mood stabilizer, is widely used in the treatment of bipolar disorder. Discontinuation of this medication during pregnancy can have serious consequences, leading to severe mood fluctuations such as mania or depression in the mother. Despite the advantage effects of lithium, its molecular impacts on neonates are still under investigation. The aim of this study is to examine the expression levels of the miR-124 gene in the offspring of rats whose mothers were exposed to lithium during pregnancy. In this experimental study, female rat received a daily dose of 30 mg/kg of lithium carbonate through their drinking water. The offsprings were divided into control and experimental groups and were maintained until the age of two months. The hippocampus and serum from the offspring were isolated for the analysis of target gene expression. Total RNA was extracted and cDNA was synthesized. The expression of miR-124 was estimated using qRT-PCR, using the ddCt and Pfaffl methods, and compared with the control group. The expression of miR-124 decreased in the hippocampal tissue of neonates whose mothers received lithium during pregnancy, while an increase in miR-124 expression was observed in serum samples. No significant distinction between the two evaluation methods was observed, even though the Pfaffl method claimed greater precision. The increase in miR-124 expression in serum and its decrease in hippocampal tissue may demonstrate complex changes in gene expression regulation and physiological responses, during stress, inflammation or metabolic changes. Concurrent analysis of gene expression in both tissue and serum could provide valuable insights into disease status and the body's biological responses, enabling scientists to gain a better understanding of the treatment process.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201429"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Superoxide dismutase gene expression and promoter methylation as biomarkers for type 2 diabetes mellitus","authors":"Ashwin Kumar Shukla , Komal Awasthi , Kauser Usman , Monisha Banerjee","doi":"10.1016/j.humgen.2025.201427","DOIUrl":"10.1016/j.humgen.2025.201427","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and altered gene expression, particularly the antioxidant defense genes named as <em>SOD1</em> and <em>SOD2</em>. These enzymes serve a significant function in mitigating oxidative damage, and their regulation may be significantly influenced by epigenetic modifications, including DNA methylation.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the promoter methylation status and expression levels of <em>SOD1</em> and <em>SOD2</em> genes in T2DM patients compared to healthy controls, to explore their potential as molecular biomarkers for T2DM.</div></div><div><h3>Methodology</h3><div>A total of 84 T2DM patients and 60 healthy controls were enrolled. Methylation-specific PCR (MSP) was applied to investigate the promoter methylation status of <em>SOD1</em> and <em>SOD2</em> genes, while real-time PCR was utilized to evaluate the expression levels of these genes in whole blood samples. Statistical analyses were performed to compare results between the T2DM group and the control group.</div></div><div><h3>Results</h3><div>The study revealed significant downregulation of both <em>SOD1</em> and <em>SOD2</em> gene expression in T2DM patients compared to controls, with <em>p</em>-values of 0.001 for both genes. Methylation analysis indicated increased promoter methylation of <em>SOD2</em> in T2DM subjects, whereas <em>SOD1</em> did not show any significant difference in the methylation status.</div></div><div><h3>Conclusion</h3><div>Our findings highlighted the critical role of reduced <em>SOD1</em> and <em>SOD2</em> expression in oxidative stress associated with T2DM. Although <em>SOD2</em> downregulation was observed, the lack of significant differences in methylation frequency between patients and controls indicated that it may not serve as a definitive biomarker by itself. Therefore, the potential influence of methylation on <em>SOD2</em> transcription warrants further investigation. Understanding these mechanisms could lead to novel therapeutic strategies targeting oxidative stress in diabetes management and at the same time improve our knowledge regarding the role of epigenetic factors in metabolic diseases.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201427"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing network analysis with supervised machine learning and mendelian randomization with unsupervised machine learning to identify core phase separation biomarkers in autoimmune insulin receptoropathy","authors":"Chuyu Liang , Zhaoxia Yu , Qiuyi Liang , Ziran Zeng , Rongguan Ma , Wenyan Xie , Xiao Zhu","doi":"10.1016/j.humgen.2025.201455","DOIUrl":"10.1016/j.humgen.2025.201455","url":null,"abstract":"<div><h3>Background</h3><div>Recent research has focused on the link between phase separation genes and immunity, alongside their potential role in insulin signaling modulation. Autoimmune insulin receptoropathy (AIR), characterized by sporadic hypoglycemia, lacks reliable molecular markers for early detection.</div></div><div><h3>Methods</h3><div>Phase separation genes associated with AIR were analyzed using differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) explored biological differences. A protein-protein interaction (PPI) network and machine learning (SVM-REF, RandomForest) identified core phase separation genes. Functional insights were gained through correlation, differential expression, and single-gene GSEA analyses. Marker gene activity was assessed via single-sample GSEA. Mendelian randomization (MR) examined potential causal links between DO results and the disease, validating associations with phase separation genes. Unsupervised machine learning reinforced the findings.</div></div><div><h3>Results</h3><div>Differential gene expression and WGCNA identified 2944 differentially expressed genes and 18 co-expression modules in AIR. The darkturquoise module, showing a potential inverse relationship with disease status, was selected for further analysis. GSEA revealed up-regulated pathways such as Inositol phosphate metabolism and down-regulated pathways like Drug metabolism. PPI network and machine learning analyses identified 10 core genes closely linked to AIR, demonstrating significant predictive capability and potential as early diagnostic biomarkers.</div></div><div><h3>Conclusions</h3><div>The phase separation genes linked to AIR show strong disease associations, offering potential for early prediction and improved clinical management.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201455"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenePub Date : 2025-09-01Epub Date: 2025-06-16DOI: 10.1016/j.humgen.2025.201435
Hwa Chia Chai, Kek Heng Chua
{"title":"Autophagy protein 5 (ATG5) rs573775 protects Malaysian Malay women from systemic lupus erythematosus","authors":"Hwa Chia Chai, Kek Heng Chua","doi":"10.1016/j.humgen.2025.201435","DOIUrl":"10.1016/j.humgen.2025.201435","url":null,"abstract":"<div><h3>Objective</h3><div>Autophagy is one of the critical cellular processes implicated in the pathogenesis of SLE. Polymorphisms in the autophagy-related genes have been associated with increased susceptibility to SLE, particularly variations in the autophagy protein 5 (<em>ATG5</em>) gene which has been associated with SLE in several populations. This case-control study aimed to investigate the association between polymorphisms in <em>ATG5</em> and SLE in Malaysian population.</div></div><div><h3>Methods</h3><div>Tetra primer amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to genotype <em>ATG5</em> rs6937876, rs4945747, rs573775, rs2245214 and rs548234 in 233 SLE patients and 224 healthy controls, collected from 2000 to 2015.</div></div><div><h3>Results</h3><div>In the overall Malaysian population, AG genotype (adjusted <em>p</em> = 0.013, OR = 1.327, 95 % CI: 1.040 to 1.695) of rs6937876 were significantly associated with increased SLE susceptibility. The dominant model (AG + AA) (adjusted <em>p</em> = 0.006, OR = 0.671, 95 % CI: 0.464 to 0.972), additive model (adjusted <em>p</em> = 0.005, OR = 0.462, 95 % CI: 0.291 to 0.733), and minor A allele (adjusted <em>p</em> = 0.007, OR = 0.628, 95 % CI: 0.447 to 0.882) of rs573775 significantly associated with Malay population by providing protection against SLE.</div></div><div><h3>Conclusion</h3><div>The SNPs in <em>ATG5</em> seem to not only conferring SLE susceptibility to the Malaysian population but also protect them from SLE. Gene expression of these SNPs and their interactions with upstream or downstream genes and microenvironment in the Malaysian population, especially Malays, is worth further study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201435"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of microRNAs carried by exosomes in glioblastoma microenvironment","authors":"Ayşe Keskin Günay , Zeynep Demirel , Nilay Dinçkurt , Esranur Kopal , Pınar Obakan Yerlikaya","doi":"10.1016/j.humgen.2025.201423","DOIUrl":"10.1016/j.humgen.2025.201423","url":null,"abstract":"<div><div>Glioblastoma (GBM) is an extremely aggressive type of glioma affecting the central nervous system (CNS). Patient survival is typically less than one year and decreases with various mutations, deletions, and amplifications. The treatment of GBM is usually challenging since drug candidates that can cross the blood-brain barrier with low side effects are limited. The initial treatment for GBM involves surgical resection, followed by radiotherapy and administration of temozolomide (TMZ) as the primary adjuvant therapy. Following TMZ treatment, most patients experience tumor recurrence due to TMZ resistance within the first year. Given the intratumoral heterogeneity, elucidating the tumor microenvironment (TME) is paramount. Exosomes, a class of extracellular vesicles (EVs) released by cells into TME, are responsible for intercellular communication. The content of exosomes, originating from early endosomes and then from late endosomes, is exceptionally rich in oncogenic proteins, angiogenic factors, coding, and non-coding RNA, such as microRNAs (miRNAs). Exosomal miRNAs are critical in driving GBM pathogenesis. They contribute to disease progression, metastasis, cancer development, angiogenesis, and drug resistance. Additionally, exosomal miRNAs influence the cell migration, proliferation, and differentiation of glioma cells, making them potential biomarkers for diagnosis, prognosis, and therapeutic response prediction. This review discusses exosomal miRNA functions in GBM progression and highlights their potential clinical applications. Also, this review summarizes available databases for identifying exosome-associated miRNAs and exploring their functional roles in GBM.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201423"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenePub Date : 2025-09-01Epub Date: 2025-07-23DOI: 10.1016/j.humgen.2025.201454
Rajesh Kumar, Srividya Shivakumar
{"title":"Harnessing apigenin for breast cancer treatment: Current insights","authors":"Rajesh Kumar, Srividya Shivakumar","doi":"10.1016/j.humgen.2025.201454","DOIUrl":"10.1016/j.humgen.2025.201454","url":null,"abstract":"<div><div>Breast cancer (BC) continues to be the world's leading cause of mortality for women. Despite advancements in cancer treatments such as radiation, hormone therapy, chemotherapy, and targeted therapy, these methods often have significant adverse effects and damage healthy cells. Keeping in view these limitations, there is an urgent need to produce safe, accessible, and efficient breast anticancer treatments. Apigenin (API), a flavonoid derived from edible plants, has garnered considerable attention in recent years. In silico, in vitro, and in vivo investigations, API has shown encouraging chemopreventive properties. In particular, it has been demonstrated that API inhibits the growth of cancer cells, trigger apoptosis, and alter key signaling pathways that involved to the onset of cancer. With regard to BC and cancer stem cells (CSCs), the objective of this review is to present a comprehensive outline of the recent study on API, clarifying its mechanisms of action, pharmacokinetics, therapeutic efficacy, bioavailability, cytotoxicity and potential as a supplement to conventional cancer therapies. The information provided will be helpful to researchers and medical professionals who are interested in learning more about alternative cancer treatments.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201454"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenePub Date : 2025-09-01Epub Date: 2025-05-21DOI: 10.1016/j.humgen.2025.201425
Laras Pratiwi , Galih Januar Adytia , Henry Sutanto
{"title":"High-throughput genomic profiling in chronic myelogenous leukemia: How far have we come, and what lies ahead?","authors":"Laras Pratiwi , Galih Januar Adytia , Henry Sutanto","doi":"10.1016/j.humgen.2025.201425","DOIUrl":"10.1016/j.humgen.2025.201425","url":null,"abstract":"<div><div>Chronic Myelogenous Leukemia (CML) is a hematological malignancy characterized by the <em>BCR::ABL1</em> fusion gene, a hallmark of its pathogenesis. Advances in molecular biology and genomic technologies have significantly enhanced our understanding of CML, with Next-Generation Sequencing (NGS) emerging as a potential transformative tool in the field. This review explores the expanding role of NGS in the diagnosis, prognostic stratification, and treatment monitoring of CML. By enabling comprehensive genomic profiling, NGS facilitates the identification of genetic mutations and clonal evolution, offering insights beyond traditional diagnostic methods. Additionally, the application of NGS in detecting treatment-resistant mutations and monitoring minimal residual disease (MRD) underscores its utility in tailoring precision therapies. However, challenges such as technical complexities, integration into clinical workflows, and cost constraints remain barriers to widespread adoption. This review highlights the clinical implications of NGS in CML management and discusses future directions, including emerging sequencing technologies and potential synergies with advanced analytics. As NGS continues to evolve, its role in shaping personalized medicine and improving patient outcomes in CML is becoming increasingly evident. This review provides a comprehensive overview of these developments while addressing the current limitations and opportunities for future research.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201425"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenePub Date : 2025-09-01Epub Date: 2025-05-27DOI: 10.1016/j.humgen.2025.201426
Marcos Jessé Abrahão Silva , Sebastião Kauã de Sousa Bispo , Rebecca Lobato Marinho , Eliete Costa da Cruz , Thiago Pinto Brasil , Caroliny Soares Silva , Yan Corrêa Rodrigues , Cristiane Cunha Frota , Diana da Costa Lobato , Lilian Cristina Santos Sinfrônio da Silva , Everaldina Cordeiro dos Santos , Ana Judith Pires Garcia , Luana Nepomuceno Gondim Costa Lima
{"title":"Functional and structural characterization of COVID-19 risk-associated exonic SNPs and identification of novel therapeutic sites: An in silico analysis","authors":"Marcos Jessé Abrahão Silva , Sebastião Kauã de Sousa Bispo , Rebecca Lobato Marinho , Eliete Costa da Cruz , Thiago Pinto Brasil , Caroliny Soares Silva , Yan Corrêa Rodrigues , Cristiane Cunha Frota , Diana da Costa Lobato , Lilian Cristina Santos Sinfrônio da Silva , Everaldina Cordeiro dos Santos , Ana Judith Pires Garcia , Luana Nepomuceno Gondim Costa Lima","doi":"10.1016/j.humgen.2025.201426","DOIUrl":"10.1016/j.humgen.2025.201426","url":null,"abstract":"<div><div>The COVID-19 pandemic has highlighted the critical need for effective therapeutic strategies against viral infections, prompting research on the functional characterization of risk-associated single nucleotide polymorphisms (SNPs). This study aimed to analyze exonic SNPs that influence individual susceptibility to COVID-19 through an <em>in silico</em> approach. Using a comprehensive methodology, SNPs were retrieved from databases such as Science Direct and PubMed, categorized into intronic, exonic, UTR, splice site, and intergenic types, with a focus on exonic SNPs. Functional analyses were performed using various bioinformatics tools to assess the effects of synonymous and non-synonymous SNPs on mRNA structure, protein stability, protein function, and potential therapeutic sites. The results revealed significant insights into the impact of specific SNPs on COVID-19 susceptibility. For example, the synonymous SNP rs12252 of <em>IFITM3</em> was found to have a moderate impact on mRNA structure and binding affinity for microRNAs, while non-synonymous SNPs exhibited varying degrees of functional consequences, with eight variants predicted to be deleterious (with emphasis on the <em>TYK2</em> SNP rs34536443 that was predicted to be deleterious in all analyzes). This approach facilitated the identification of novel therapeutic targets. Finally, this research highlights the importance of understanding genetic variations in developing personalized medicine approaches for COVID-19.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201426"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrated meta-analysis reveals circulating miRNA panel for hepatocellular carcinoma diagnosis","authors":"Isbah Ashfaq , Naz Fatima , Nadeem Sheikh , Asima Tayyeb","doi":"10.1016/j.humgen.2025.201440","DOIUrl":"10.1016/j.humgen.2025.201440","url":null,"abstract":"<div><h3>Objective</h3><div>HCC is the leading cause of deaths primarily in patients with liver ailment. Considering its incidence rate as global burden, efficacy of multiple drugs have changed the landscape of overall management of this disease. Recently, diagnosis based on non-invasive microRNAs has impacted the clinical outcomes of various cancers. The current study focuses on identifying potential non-invasive biomarkers for the early detection of HCC.</div></div><div><h3>Methods</h3><div>This research underscores the significance of a unique panel of circulating miRNAs observed at three distinct stages of liver disease: chronic hepatitis, liver cirrhosis, and HCC. The dataset, comprising microarray profiles of circulating miRNAs, was acquired from GEO repository. The DE-miRNAs and their overlapping at different stages of liver diseases were identified. The bioinformatics analyses were performed and statistical analysis was conducted to identify the significant and unique panel of circulating miRNAs.</div></div><div><h3>Results</h3><div>Altogether, 3 miRNAs such as hsa-miR-1290, hsa-let-7a-5p, and hsa-mir-16-5p were found with AUC ≥0.80 and <em>P</em>-value ≤0.05. Furthermore, pathways enrichment analysis revealed association of genes and signalling pathways.</div></div><div><h3>Conclusion</h3><div>In conclusion, suggested panel of circulating miRNAs may provide a potential approach for non-invasive diagnosis of HCC. These miRNAs could serve as timely indicators for detecting HCC, thereby offering a promising strategy for the effective management of this condition.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201440"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human GenePub Date : 2025-09-01Epub Date: 2025-06-02DOI: 10.1016/j.humgen.2025.201430
Maryam Mozafar , Seyed Amir Mirmotalebisohi , Ahmad Reza Shahverdi , Hakimeh Zali
{"title":"Investigating molecular aspects of SARS-CoV-2 neurological manifestations, a systems biology approach","authors":"Maryam Mozafar , Seyed Amir Mirmotalebisohi , Ahmad Reza Shahverdi , Hakimeh Zali","doi":"10.1016/j.humgen.2025.201430","DOIUrl":"10.1016/j.humgen.2025.201430","url":null,"abstract":"<div><h3>Objectives</h3><div>Amid the COVID-19 pandemic, reported neurological symptoms and potential syndromes such as ischemic stroke, seizure, and encephalitis highlight the neurological impact of SARS-CoV-2. We employed a systems biology approach to analyze omics transcriptional data, exploring the molecular mechanisms underlying neurological complications in COVID-19.</div></div><div><h3>Methods</h3><div>We retrieved post-mortem brain data of COVID-19 patients from the gene expression omnibus (GEO) dataset and constructed protein-protein interaction (PPI) networks for differentially expressed genes (DEGs) in the brain cortex and choroid plexus. Topologically crucial genes were identified, and MCODE clusters were analyzed for functional enrichment using the STRING database. Genes related to neurological symptoms (headache, seizure, stroke, meningitis, encephalitis) were extracted from the Comparative Toxicogenomics Database (CTD), and their associations with MCODE clusters were assessed via Fisher's exact test. Crucial gene interactions with FDA-approved drugs were also investigated.</div></div><div><h3>Results</h3><div>We identified a cluster of heat shock protein (HSP) genes (HSP90AA1, HSPA1A, HSPA1B, HSPB1, HSPH1, HSPA5, DNAJB1, FKBP5) significantly correlated with all neurological manifestations. KEGG pathway enrichment showed associations with immune processes, neurodegenerative diseases (Parkinson's, Alzheimer's, Huntington's), virus-related pathways (Influenza A, Epstein-Barr, Measles), and pathways activated in viral infections. FKBP5, a key Hsp90 co-chaperone, interacts most with drugs that affect the nervous system in our drug-gene network.</div></div><div><h3>Conclusions</h3><div>Shedding light on the molecular mechanisms behind COVID-19 neurological manifestations and possible drugs could pave the way for better managing future neurotrophic viruses.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201430"},"PeriodicalIF":0.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}