Open Medicine最新文献

{"title":"METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2.","authors":"Xiujuan Chen, Qipeng Ling, Jie Xu, Yunyao Ye, Lili Dong","doi":"10.1515/med-2025-1191","DOIUrl":"https://doi.org/10.1515/med-2025-1191","url":null,"abstract":"<p><p>We aimed to explore the regulatory effects of methyltransferase-like 3 (METTL3) on diabetic retinopathy (DR) by regulating the m6A modification of <i>SOX2</i> mRNA and elucidating the underlying molecular mechanism. The DR model was established by stimulating human retinal endothelial cells (HRECs) with high glucose (HG). METTL3, insulin-like growth factor 2 binding protein 2 (IGF2BP2), and SOX2 levels in the sera of patients with DR and HRECs were determined using qRT-PCR and western blotting. Moreover, the interactions between SOX2 and METTL3 or IGF2BP2 were confirmed using RNA-binding protein immunoprecipitation (RIP) experiments. Furthermore, HRECs proliferation and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The protein level of cleaved-caspase3 and caspase3 in HRECs were evaluated using western blotting. The results indicated that the expression of METTL3, IGF2BP2, and SOX2 was notably decreased in the serum of patients with DR, as well as in HRECs under HGs. RIP further verified the relationship between <i>METTL3</i> and <i>SOX2</i> mRNA expression. HG treatment inhibited HREC viability, increased apoptosis, and enhanced cleaved-caspase3 expression and cleaved-caspase3/caspase3 ratio. Upregulation of <i>METTL3</i> significantly restored the effects of HG, whereas <i>SOX2</i> knockdown partially reversed the regulatory effects of METTL3 on HRECs. In summary, METTL3 blocks the progression of DR by regulating m6A modification on <i>SOX2</i> mRNA.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251191"},"PeriodicalIF":1.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19.","authors":"Biljana Popovska Jovičić, Ivana Raković, Nemanja Đorđević, Jagoda Gavrilović, Predrag Čanović, Ružica Radojević Marjanović, Sara Petrović, Katarina B Milosavljević, Ana Divjak, Nenad Stanković, Milan Paunović, Miloš Z Milosavljević","doi":"10.1515/med-2025-1246","DOIUrl":"https://doi.org/10.1515/med-2025-1246","url":null,"abstract":"<p><strong>Study objective: </strong>The main objective of this study was to investigate the association between CD4+ and CD8+ lymphocyte values and disease severity, need for oxygen therapy and disease outcomes.</p><p><strong>Design: </strong>The research was designed as a cross-sectional observational study.</p><p><strong>Setting: </strong>This study was conducted at the Clinic for Infectious Diseases, University Clinical Center Kragujevac, as a COVID-19 treatment center.</p><p><strong>Participants: </strong>The study group consisted of a total of 101 adult hospitalized patients with confirmed COVID-19 infection, excluding patients under 18 years of age, patients with malignant diseases, tuberculosis, hepatitis, immune disorders, pregnant women, or HIV-positive patients. SARS-CoV2 infection was diagnosed by rapid antigen tests or real-time reverse transcription polymerase chain reaction from a nasal swab.</p><p><strong>Interventions: </strong>The patients were classified into two groups based on oxygen therapy needs, disease severity, and disease outcomes.</p><p><strong>Results and conclusions: </strong>Low CD4+ and CD8+ T cell values were associated with severe clinical presentation, more need for oxygen therapy as well as poor disease outcome. Receiver operating characteristic analysis provided cutoff values to support predicting the aforementioned variables, establishing CD4+ and CD8+ values as significant prognostic biomarkers. Future studies should be aimed at identifying factors that lead to gender differences in the immune response.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251246"},"PeriodicalIF":1.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease.","authors":"Hong Yu, Min Wan, Hong Li, Xing Liu","doi":"10.1515/med-2025-1241","DOIUrl":"https://doi.org/10.1515/med-2025-1241","url":null,"abstract":"<p><strong>Background: </strong>Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation and is closely associated with obesity, diabetes, and hyperlipidemia.</p><p><strong>Objectives: </strong>This study explores the effects of pachymaran on NAFLD induced by a high-fat diet (HFD) in a murine model.</p><p><strong>Methods: </strong>Thirty male C57BL/6 mice were allocated into five groups: normal diet (ND), NAFLD, and high-, medium-, and low-dose pachymaran (200, 100, and 50 mg/kg, respectively). All groups except the ND were fed a HFD to induce NAFLD. The pachymaran groups received daily intragastric pachymaran for eight weeks. Post-treatment, liver weight were recorded, serum indices assessed, and hepatic pathology evaluated via histological and Oil Red O staining. Adenylate-activated protein kinase (AMPK) gene expression was analyzed through western blotting.</p><p><strong>Results: </strong>The body weight and liver gain (87.8 and 23.0%) in the high-dose pachymaran group were significantly less than those (154.2 and 82.0%) in the NAFLD group (<i>P</i> < 0.05). Fat content and serum indices improvements correlated with increased pachymaran doses. Histological analyses indicated significant alleviation of hepatocyte hypertrophy and ballooning steatosis in treated groups. Oil Red O staining confirmed a substantial decrease in hepatic lipid droplets, and western blot results indicated a significant increase in AMPK phosphorylation following treatment (<i>P</i> < 0.05).</p><p><strong>Conclusions: </strong>Pachymaran effectively mitigated fat accumulation, hepatocyte degeneration, and injury in mice with diet-induced NAFLD, likely through modulation of the AMPK pathway.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251241"},"PeriodicalIF":1.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis.","authors":"Nedim Uzun, Ozgecan Gundogar, Naile Misirlioglu, Emine Yildirim, Neslin Sahin, Seyma Dumur, Hafize Uzun","doi":"10.1515/med-2025-1227","DOIUrl":"https://doi.org/10.1515/med-2025-1227","url":null,"abstract":"<p><strong>Objectives: </strong>Accurate diagnosis of acute cholecystitis (AC) is critical because early laparoscopic cholecystectomy significantly reduces complications and mortality. This study evaluates the predictive value of inflammatory indices and hematological markers in diagnosing AC.</p><p><strong>Methods: </strong>A retrospective review was performed on early laparoscopic cholecystectomy cases at the Gaziosmanpaşa Training and Research Hospital in Istanbul between August 2013 and August 2023. Patient demographics, preoperative laboratory values, inflammatory indices - including neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) - were evaluated, along with hospital length of stay and histopathological outcomes.</p><p><strong>Results: </strong>Among 249 patients, 34 (13.6%) were diagnosed with AC, comprising 76 males (30.5%) and 173 females (69.5%), with a mean age of 48.9 ± 14.6 years. The median hospital length of stay was 3 days (range: 1-21). Significant elevations in both the SIRI and neutrophil count were observed in AC cases compared to controls (<i>P</i> < 0.001). ROC (receiver operating characteristic) curve analysis demonstrated comparable diagnostic performance for the SIRI (AUC = 0.746; 95% CI: 0.658-0.835; optimal cutoff: 1.98) and neutrophil count (AUC = 0.746; 95% CI: 0.658-0.835; optimal cutoff: 7.1 × 10³/μL) in predicting AC.</p><p><strong>Conclusions: </strong>The SIRI and neutrophil count are reliable markers that can improve the diagnostic accuracy and guide early management of AC.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251227"},"PeriodicalIF":1.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis.","authors":"Zhiyan Xu, Kaihua Zhong, Weiyuan Chen, Huixia Lan, Weifeng Zhong, XiaoHong Wang, Mu Chen, Bin Pan","doi":"10.1515/med-2025-1236","DOIUrl":"https://doi.org/10.1515/med-2025-1236","url":null,"abstract":"<p><strong>Background: </strong>Postoperative cognitive dysfunction (POCD) is driven in part by microglial activation and the resulting neuroinflammatory response. Emerging evidence suggests that microRNAs regulate key inflammatory pathways in the central nervous system. In this study, we examined the role of the mmu‑miR‑125a/TRAF6 signaling axis in microglial activation under inflammatory conditions induced by lipopolysaccharide (LPS) and surgical trauma and evaluated whether dexmedetomidine (DEX) modulates this pathway to alleviate POCD.</p><p><strong>Methods: </strong>Murine microglial cells were treated with LPS to induce activation. Expression levels of mmu‑miR‑125a and TRAF6 were quantified by qRT‑PCR and Western blotting. Bioinformatic prediction of miRNA binding sites was performed, and a luciferase reporter assay was used to confirm direct targeting of TRAF6 by mmu‑miR‑125a. Adult mice underwent standardized surgical trauma to induce POCD. Brain tissues were analyzed for microglial activation markers, cytokine levels, and expression of mmu‑miR‑125a and TRAF6. DEX was administered in both <i>in vitro</i> and <i>in vivo</i> models. The effects on cytokine release, microglial activation, and the mmu‑miR‑125a/TRAF6 axis were assessed.</p><p><strong>Results: </strong>Our findings revealed significant alterations in the expression levels of TRAF6 and mmu-miR-125a during LPS-induced microglial activation. Through bioinformatics analysis and experimental validation, we identified TRAF6 as a direct target of mmu-miR-125a. The mmu-miR-125a/TRAF6 axis was found to be crucial for regulating microglial activation both <i>in vitro</i>, using an LPS-induced model, and <i>in vivo,</i> using a surgical trauma-induced POCD model. Moreover, we demonstrated that DEX, an alpha-2 adrenergic receptor agonist, effectively modulated the inflammatory cytokine release by targeting the mmu-miR-125a/TRAF6 axis in both models. The administration of DEX significantly suppressed microglial activation and TRAF6 expression, effects that were reversed by the inhibition of mmu-miR-125a.</p><p><strong>Conclusion: </strong>Our study provides new insights into the molecular mechanisms underlying microglial activation and highlights the therapeutic potential of targeting the mmu-miR-125a/TRAF6 axis to alleviate neuroinflammation by the administration of DEX in POCD.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251236"},"PeriodicalIF":1.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of serum metabolomics in patients with different types of chronic heart failure.","authors":"Bingzhang Jie, Qiang Li, Ling Han, Liwei Chen, Ming Yang","doi":"10.1515/med-2025-1210","DOIUrl":"https://doi.org/10.1515/med-2025-1210","url":null,"abstract":"<p><strong>Background: </strong>Heart failure remains a major public health issue, and there are still no reliable biomarkers for left ventricular ejection fraction (LVEF).</p><p><strong>Objective: </strong>To screen for differential metabolites in the blood of HFpEF, HFmrEF, and HFrEF patients based on metabolomics analysis of their blood samples.</p><p><strong>Methods: </strong>Total 44 patients in HFpEF group, 30 patients in HFmrEF group, and 36 patients in HFrEF group were selected. The blood metabolites were analyzed by liquid chromatography high-resolution mass spectrometry and classified by principal component analysis, and then potential biomarker were screened. Partial least squares discriminant analysis was used to model and investigate the predictive ability of biomarkers for LVEF.</p><p><strong>Results: </strong>Blood metabolite profiles of HFpEF, HFmrEF, and HFrEF groups could be well distinguished, and seven potential biomarkers were identified, such as phosphatidylcholine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylcholine, ceramide, sphingosine, and sphingomyelin. Four metabolic pathways, such as glycerol phospholipid metabolic pathway, linoleic acid metabolic pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism pathway were identified, among which glycerol phospholipid metabolism pathway was the most significant.</p><p><strong>Conclusion: </strong>The changes in glycerol phospholipid metabolism pathway may help identify HFpEF, HFmrEF, and HFrEF.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251210"},"PeriodicalIF":1.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Giant right atrial hemangioma presenting with ascites: A case report.","authors":"Antonio Salsano, Giacomo Perocchio, Antonio Guadagno, Paolo Nozza, Tommaso Regesta, Francesco Santini","doi":"10.1515/med-2025-1169","DOIUrl":"https://doi.org/10.1515/med-2025-1169","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac hemangiomas are slow-growing benign tumours of the heart. Patients may be asymptomatic or present a multitude of signs or symptoms.</p><p><strong>Methods: </strong>We report herein the case of a 72-year-old woman with a giant right atrial mass. The patient suffers from abdominal swelling related to ascites. The histological examination of the tranjugular biopsy suspected an atrial myxoma.</p><p><strong>Results: </strong>The patient was scheduled for surgical excision of the cardiac tumour. Radical resection of a 13 cm mass was performed. The histological diagnosis revealed cardiac hemangioma.</p><p><strong>Conclusion: </strong>Cardiac hemangiomas can rarely grow larger than 5 cm, cause few symptoms, and are easily confused with atrial myxomas. Hepatomegaly and ascites may be signs of cardiac hemangioma.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251169"},"PeriodicalIF":1.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"The progress of autoimmune hepatitis research and future challenges\".","authors":"Yang Zhang, Dehe Zhang, Ling Chen, Jing Zhou, Binbin Ren, Haijun Chen","doi":"10.1515/med-2025-9993","DOIUrl":"10.1515/med-2025-9993","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1515/med-2023-0823.].</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20259993"},"PeriodicalIF":1.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance.","authors":"Jianli Gong, Xianguo Xu, Jianrong Zhu","doi":"10.1515/med-2025-1234","DOIUrl":"10.1515/med-2025-1234","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To establish a multi-level blood type identification system, comprehensively analyze the distribution characteristics and genetic polymorphisms of multi-system rare blood types in foreign blood donors, explore the application value of DNA sequencing technology in rare blood type screening, and evaluate its clinical significance in complex transfusion patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Blood samples from 277 foreign blood donors who participated in voluntary blood donation in Yiwu City were prospectively collected from June 2021 to March 2023. Serological typing of 24 antigens from 11 red blood cell blood group systems (ABO, Rh, Duffy, MNS, Kidd, Kell, Lutheran, P1PK, Lewis, H, and Diego) was performed using microcolumn agglutination and tube methods. First-generation sequencing technology was used to perform whole-exome sequencing of Duffy, Kell, Ss/GYPB, and Diego genes on screened rare phenotype samples to analyze genetic polymorphism characteristics. Key mutation sites were verified using multiplex PCR-sequencing. A rare blood type DNA database was established and compared with the international blood group gene database (BGMUT). Confirmed rare blood type units were preserved through programmed freezing, and their clinical application effects were tracked and analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The 277 foreign blood donors were primarily from the Middle East and South Asia (71.8%), with major source countries including Syria (56 cases, 20.22%), Yemen (49 cases, 17.69%), Pakistan (24 cases, 8.66%), Iraq (20 cases, 7.22%), India (15 cases, 5.42%), Iran (14 cases, 5.05%), Mali (11 cases, 3.97%), and Jordan (10 cases, 3.61%). In blood type distribution, Fya antigen expression was highest among Indian (100%) and Pakistani (87.50%) donors; 63 cases of Fy(a-b-) were found, most commonly in donors from Mali and Yemen. S antigen expression was highest in donors from Syria (60.71%), India (60.00%), and Pakistan (58.33%); 47 cases of S+s- were detected. Additionally, 12 cases of Lua+ were found, distributed among Syria (3 cases), Iraq (2 cases), Yemen (2 cases), Jordan (2 cases), etc.; 5 cases of Kpa+ were from Yemen (2 cases), Pakistan, Iraq, and Jordan (1 case each). DNA sequencing revealed that GATA-1 promoter region mutation (c.-67T&gt;C) in the Duffy gene was the primary molecular basis for the Fy(a-b-) phenotype, accounting for 96.8% (61/63). Multivariate analysis demonstrated significant clustering of blood group phenotypes by geographical regions (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), with the first two principal components explaining 78.3% of the variance in distribution patterns. Genotype-phenotype correlation analysis showed a concordance rate of 99.2% (248/250). During the study period, 41 rare phenotype blood units (74U) were screened and cryopreserved, including 14 units (24.5U) of Fy(a-b-), 25 units (45.5U) of Fy(a-b+), and 2 units (4.0U) of s(-). In clinical application, these units were successfully used in three di","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251234"},"PeriodicalIF":1.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The identification of novel missense variant in <i>ChAT</i> gene in a patient with gestational diabetes denotes plausible genetic association.","authors":"Oluwafemi G Oluwole, Afolake Arowolo, Ezekiel Musa, Naomi Levitt, Mushi Matjila","doi":"10.1515/med-2025-1225","DOIUrl":"10.1515/med-2025-1225","url":null,"abstract":"<p><strong>Introduction: </strong>Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with a 50% increase in subsequent risk for type 2 diabetes. There is increasing interest in identifying biomarkers that may facilitate the stratification of subsequent type 2 diabetes risk among women with GDM. In this study, we considered the choline acetyltransferase (<i>ChAT</i>) gene. CHAT plays a critical role in acetylcholine synthesis and regulates insulin secretion from the pancreatic islet to maintain glucose homeostasis.</p><p><strong>Methods: </strong>We screened for deleterious variants in the <i>ChAT</i> gene in 12 GDM patients and 10 ethnically matched controls from a South African cohort. We isolated DNA from the placental samples of these patients and performed DNA sequencing of the protein-coding region of the <i>ChAT</i> gene. Sequence alignments and variant annotations were done using UGENE software and Ensembl VEP.</p><p><strong>Results: </strong>A novel heterozygous missense variant in exon 8 of the <i>ChAT</i> gene was identified. The plausible phenotypic impact of the variant <i>ChAT</i> (NM_020549.5):c.1213C>G (p.Leu405Val) can be explained by haploinsufficiency, changing protein activities, strong transcription activity, and epigenetic repression activities of the variant. Also, structurally, the variant is located 18bp in-frame to a stop-gained variant (p.Gly411Ter). The RegulomeDB DNase expression data clearly show the identified variant in a peak expression in the spleen and placenta. This observation corroborates that the <i>ChAT</i> gene may play an essential role in GDM.</p><p><strong>Conclusion: </strong>Taken together, the metric scores for this variant show that it could affect the functions of the gene, but more functional studies are necessary to validate these effects. Consequently, this study sets the stage for the future screening of a larger cohort and functional validation of deleterious variants to underpin the <i>ChAT</i> gene and GDM association.</p>","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"20 1","pages":"20251225"},"PeriodicalIF":1.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}