Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Lactylation-related Gene Signatures in Intracerebral Hemorrhage: Immune Infiltration, Machine Learning Biomarkers, and Molecular Pathway Insights.","authors":"Yaqun Li, Ju Gao, Yinggang Xiao, Tianfeng Huang","doi":"10.2174/0118715303434525260315181645","DOIUrl":"10.2174/0118715303434525260315181645","url":null,"abstract":"<p><strong>Introduction: </strong>Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder with high mortality and limited treatment options. Inflammation and metabolic dysregulation contribute to ICH pathology, yet their molecular underpinnings remain poorly understood. Lactylation, a recently discovered post-translational modification, is known to regulate immune and metabolic pathways. This study investigated lactylation-related genes in ICH, their relationship with immune cell infiltration, and their diagnostic potential.</p><p><strong>Methods: </strong>Gene expression data from two public datasets (GSE73378 and GSE36791) were integrated after batch correction. Differentially expressed genes (DEGs) were identified with \"limma\" and lactylation-related genes were curated from the literature. Functional enrichments were conducted via GO and KEGG. Diagnostic genes were selected using XGBoost, Random Forest, and LASSO regression. Immune cell infiltration was analyzed by ssGSEA, and unsupervised clustering defined molecular subtypes. Hemorrhage-associated genes were validated by RT-qPCR in a mouse model of hemorrhage.</p><p><strong>Results: </strong>A total of 111 lactylation-related DEGs were identified. Seven core genes demonstrated strong diagnostic performance (AUC = 0.80-0.92). ssGSEA revealed significant immune alterations associated with lactylation-related gene expression. Unsupervised clustering identified two distinct ICH subtypes with different immune and transcriptional profiles. Upstream regulators predicted PTBP1 and HNRNPD as potential transcriptional regulators. Six of the seven genes were validated in hemorrhagic mice.</p><p><strong>Discussion: </strong>These findings suggest that lactylation links metabolic dysregulation to immune responses in ICH, contributes to molecular heterogeneity, and may enable patient stratification and precision therapeutic strategies.</p><p><strong>Conclusion: </strong>Lactylation-related genes are closely linked to immune dysregulation in ICH and show promise as diagnostic biomarkers and therapeutic targets.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303434525"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679788","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 Bioinformatics Analysis of Autophagy-Related Biomarkers in Atherosclerosis and Acquired Immune Deficiency Syndrome.","authors":"Hua Zhong, Fangfang Zhang, Yupeng Wu, Yuzhu Zhang, Anxiang Sha, Zaihan Zhu, Min Bao, Dandan Sun","doi":"10.2174/0118715303453649260321063011","DOIUrl":"10.2174/0118715303453649260321063011","url":null,"abstract":"<p><strong>Introduction: </strong>Atherosclerosis (AS) and acquired immune deficiency syndrome (AIDS) are associated with autophagy-related pathways. This research was intended to ascertain the interplay between AS and AIDS through autophagy-related mechanisms and to identify potential common biomarkers.</p><p><strong>Methods: </strong>Single-cell datasets for AS and AIDS were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from each dataset were identified and then intersected with autophagy-related genes (ATGs). Functional enrichment and protein-protein interaction (PPI) network analyses were performed. Hub genes were determined via CytoHubba and MCODE. Finally, the hub genes were validated via bulk transcriptomic data. ROC curves were plotted, and their correlations with immune cell infiltration were investigated. Transcription factor networks and drug-gene interactions were implemented.</p><p><strong>Results: </strong>17 key ATGs were found, which were primarily enriched in autophagy, apoptosis, and TGF-β signaling pathways. After intersecting the 17 ATGs with DEGs using four algorithms in the Cytoscape plugin, eight genes were identified. Finally, three hub genes, encompassing GAPDH, HSPA8, and REL, were determined. ROC curves confirmed their diagnostic value. Their expression levels were markedly correlated with immune cell infiltration, and potential drugs were forecast.</p><p><strong>Discussion: </strong>This study demonstrates that GAPDH, HSPA8, and REL form a shared molecular pathway linking AS and AIDS via dysregulated autophagy, highlighting their potential as diagnostic biomarkers and therapeutic targets.</p><p><strong>Conclusion: </strong>Three hub genes, including GAPDH, HSPA8, and REL, were determined as potential biomarkers for AIDS and AS, providing insights into the molecular mechanisms of HIV-associated AS.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303453649"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147793927","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":"LGI1 Antibody-Associated Encephalitis Complicated with Sjögren's Syndrome and Acute Cerebral Infarction: A Case Report and Literature Review","authors":"Dongxiao Jiang, Yanfen Lian, Xia Zhan, Jingjing Wang, Pengjiao Xu, Yuhua Bi","doi":"10.2174/0118715303410062250729095927","DOIUrl":"10.2174/0118715303410062250729095927","url":null,"abstract":"<p><strong>Background: </strong>Anti-LGI1 antibody-associated encephalitis is a rare autoimmune neurological disorder, and primary Sjögren's syndrome is a systemic autoimmune disease with multisystem involvement. The coexistence of these conditions with acute cerebral infarction is extremely rare and highlights complex interactions between autoimmune and vascular mechanisms.</p><p><strong>Case presentation: </strong>This case report describes a middle-aged female patient diagnosed with LGI1 antibody-associated encephalitis, complicated by Sjögren's syndrome and acute cerebral infarction. The patient presented with an acute onset of symptoms, including delayed response, cognitive impairment, and right-sided weakness. Brain MRI revealed a fresh infarction in the left basal ganglia region. Blood and cerebrospinal fluid tests confirmed the presence of LGI1 antibodies, with blood anti-SS-A antibody levels at +++ and anti-SS-B antibody levels at +, as well as anti- Ro-52 antibody levels at +++.</p><p><strong>Conclusions: </strong>This report emphasizes the importance of recognizing the overlap between these conditions, as timely diagnosis and intervention can lead to better outcomes in similar cases. By examining the relationship between anti-LGI1 antibody-associated encephalitis, primary Sjögren's syndrome, and acute cerebral infarction, this paper aims to expand the understanding of the complex interactions between autoimmune encephalitis and systemic disorders.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303410062"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linderae Radix Attenuates Hyperlipidemia by Regulating Reverse Cholesterol Transport through the miR-33-PPARα/LXRα Axis.","authors":"He Ye, Weizhi Lai, Shanshan Lei, Jiexian Zhang, Ke Li, Zhisen Wang, Xunjie Zheng, Xiaohu Yang, Zhaohuan Lou","doi":"10.2174/0118715303397929251030093605","DOIUrl":"10.2174/0118715303397929251030093605","url":null,"abstract":"<p><strong>Introduction: </strong>It has been reported that miR-33 could down-regulate the key protein expression of reverse cholesterol transport (RCT) to clear excess cholesterol. Our previous studies reported that Linderae Radix (Wuyao in Chinese, WY) has a strong anti-hyperlipidemia effect by regulating RCT, but whether the regulation of WY on RCT is related to miR-33 remains unclear.</p><p><strong>Methods: </strong>In in vivo research, mice were randomly divided into five groups. miR-33 agomir was administered to hyperlipidemic (HLP) mice to establish a miR-33 over-expression model. The anti- hyperlipidemic effect of WY in mice was evaluated by serum lipid profile, hematoxylin and eosin (H&E) staining, and Oil Red O staining. <i>In vitro</i>, the effect of WY on cholesteryl ester and uptake was measured in ox-LDL-induced RAW 264.7 cells. We established cell models with either overexpression or low expression of miR-33. The effect of WY on the expression of proteins related to reverse cholesterol transport (RCT) was evaluated using RT-qPCR, Western blotting, Wes automated protein expression analysis, and multiplex immunofluorescence assays.</p><p><strong>Results: </strong>WY could significantly reduce TC, TG, and LDL-C levels and improve lipid accumulation in the liver of both HLP mice and miR-33 over-expression HLP mice. Moreover, RCT-related proteins, such as ABCA1, ABCG1, PPARα, LXRα, and farnesoid X receptor (FXR), were also increased after WY treatment. The same trend was observed <i>in vitro</i>, that WY could alleviate lipid deposition in macrophages. Compared with the miR-33 mimic group, the expression of ABCA1, ABCG1, SR-BI, and LXRα was significantly increased in RAW264.7 cells incubated with WY. Compared with the miR-33 inhibitor group, WY markedly enhanced the expression levels of ABCA1, ABCG1, LXRα, and SR-BI in cells with low miR-33 expression.</p><p><strong>Discussion: </strong>Activation of PPARα/LXRα by Linderae Radix through miR-33 inhibition represents a mechanistically distinct approach from statins or fibrates, potentially benefiting statin-intolerant patients or serving as an adjunct therapy.</p><p><strong>Conclusion: </strong>These findings suggest that WY could attenuate hyperlipidemia by regulating RCT through the miR-33-PPARα/LXRα axis.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303397929"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Islet Function in People With Different Glucose Metabolic States.","authors":"Guiling Li, Yixian Liu, Xiaoxuan Liu, Huijing Luo, Huimin Zhou, Xu Huang, Qian He, Jinhong Li, Yanv Ren, Xiaofang Zhang, Zuoliang Dong","doi":"10.2174/0118715303436762260508092256","DOIUrl":"10.2174/0118715303436762260508092256","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 Diabetes Mellitus (T2DM) is closely associated with impaired islet β-cell function. Multiple indicators can be used to evaluate islet function and insulin resistance. The aim of this study is to establish a β-cell function assessment model based on oral glucose tolerance test (OGTT) indices, providing a reference for the early diagnosis and treatment of diabetes.</p><p><strong>Methods: </strong>In this study, 30 Normal Glucose Tolerance (NGT), 43 Impaired Glucose Regulation (IGR), and 42 T2DM subjects were enrolled. The levels of blood glucose, insulin, c-peptide, and proinsulin were measured during OGTT. Insulinogenic index (IGI), C-Peptide generation Index (CPI), and proinsulinogenic index (PNI) were calculated. Fasting-state ratios, including c-peptide to glucose (CP/I), proinsulin to insulin (PI/I), and proinsulin to c-peptide (PI/CP), were calculated. The area under the curve (AUC) was analyzed for these indices and their corresponding ratios. ROC curve analysis was performed to evaluate the diagnostic value of these indicators for glucose metabolism disorders and β-cell function.</p><p><strong>Results: </strong>In the fasting state, CP/I gradually increased, while IGI and PNI gradually decreased from the NGT group to the IGR and T2DM groups. For diagnosing IGR, the AUCs of CP/I, IGI, and PNI were 0.8101, 0.762, and 0.7605; for T2DM, they were 0.8746, 0.9651, and 0.8451; and for distinguishing IGR from T2DM, they were 0.7054, 0.8200, and 0.6833, respectively.</p><p><strong>Discussion: </strong>Different indicators have different diagnostic capabilities for IGR and T2DM. The comparison of various indicators reveals pancreatic islet function across different glucose-metabolizing populations.</p><p><strong>Conclusion: </strong>CP/I, IGI, and PNI were more sensitive in reflecting impaired glucose tolerance. CP/I can reflect insulin clearance capacity, and IGI can reflect β-cell dysfunction.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303436762"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudoexfoliation Glaucoma Selective Laser for Trabeculoplasty Treatment in Vietnam.","authors":"Thanh Doan Kim, To Tran Ke, Anh Tran Cong, Tuan Le Minh, Gianna Dipalma, Luigi Santacroce, Kieu C D Nguyen, Ciro Gargiulo Isacco","doi":"10.2174/0118715303387982250905154258","DOIUrl":"10.2174/0118715303387982250905154258","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate the effectiveness of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in Vietnamese patients with pseudoexfoliation glaucoma (PXG).</p><p><strong>Methods: </strong>This prospective, comparative study included a total of 64 eyes from PXG patients who had not previously received any antiglaucomatous medication. Patients were categorized into two groups: Group 1 consisted of 32 eyes treated with SLT as the initial therapy, while Group 2 comprised 32 eyes treated with Tafluprost 0.0015%.</p><p><strong>Results: </strong>The baseline IOP before treatment ranged from 22 to 26 mmHg. There were no significant differences between the two groups in terms of mean cup/disc (C/D) ratio and retinal nerve fiber layer (RNFL) thickness. At the final visit, the mean percentage reduction of IOP was 26.73% in Group 1 and 27.15% in Group 2.</p><p><strong>Discussion: </strong>SLT significantly reduced IOP in PXG patients, with outcomes comparable to Tafluprost. Treatment was more successful in eyes with higher trabecular pigmentation and early- stage glaucoma. Structural and functional parameters remained stable over 12 months. Side effects, including mild itchiness, IOP spikes, and anterior chamber reactions, were transient and manageable. No vision-threatening complications occurred, confirming SLT as a safe and effective first-line option for PXG in Vietnamese patients.</p><p><strong>Conclusion: </strong>SLT can be effectively used as a primary treatment for PXG. In cases of recurrent IOP elevation, a second SLT procedure can be administered alone or in combination with other medications.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303387982"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294878","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":"Bioinformatics-based Mechanisms of Lipid Metabolism and Endoplasmic Reticulum Stress in Coronary Artery Disease.","authors":"Lili Ye, Huaiyu Ruan, Qinyun Chen, Yiming Chen, Ruiyan Wang, Jing Zhou, Jian Wang, Mengyu He, Ke Wang, Yuli Huang, Feng Wang","doi":"10.2174/0118715303432896251016035431","DOIUrl":"10.2174/0118715303432896251016035431","url":null,"abstract":"<p><strong>Introduction: </strong>Lipid metabolism and endoplasmic reticulum stress (ERS) are crucial in coronary artery disease (CAD) pathogenesis, but the exact mechanisms remain unclear. This study aims to systematically investigate the molecular interplay between lipid metabolism and ERS in CAD.</p><p><strong>Methods: </strong>Lipid metabolism-related genes (LRGs), ERS-related genes (ER-RGs), and the bulk RNA-seq dataset were collected related to CAD. Machine learning algorithms and receiver operating characteristic (ROC) analysis were then integrated to identify key genes. Subsequent analyses included gene set enrichment analysis (GSEA), immune cell infiltration profiling, regulatory network construction, and drug prediction. The causal relationship between key genes and CAD was analyzed by Mendelian randomization. Finally, the mRNA expression levels of key genes in clinical samples were verified with the help of qPCR experiments.</p><p><strong>Results: </strong>12 candidate genes were identified by integrating LASSO, SVM-RFE, and Boruta algorithms. The ROC analysis prioritized three high-confidence diagnostic key genes (NFKB1, LPIN1, and SEC24B). Furthermore, these key genes exhibited significant associations with the CAD immune microenvironment; notably, NFKB1 demonstrated a strong positive correlation with memory-activated CD4+ T cells. Furthermore, MR analysis showed SEC24B polymorphisms conferred reduced CAD risk (OR = 0.85), consistent with its protective expression pattern. The qPCR results show significant downregulation of both LPIN1 and NFKB1 in CAD patients.</p><p><strong>Discussion: </strong>Our findings suggest that NFKB1, LPIN1, and SEC24B play pivotal roles in CAD by linking lipid metabolism with endoplasmic reticulum stress and modulating immune responses. The downregulation of NFKB1 and LPIN1 in CAD patients, together with the protective effect of SEC24B polymorphisms, highlights a complex interplay between metabolic and inflammatory pathways. These insights not only improve our understanding of CAD pathogenesis, but also point to potential molecular targets for precise therapeutic interventions.</p><p><strong>Conclusion: </strong>This study elucidates the pathogenic mechanisms of L-ER RGs in CAD development, identifying NFKB1, LPIN1, and SEC24B as key molecular mediators. It not only reveals their roles in immune regulation and metabolic pathways but also provides actionable targets for precision therapeutics in CAD management.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303432896"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440528","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":"Functions of Estrogen and Estrogen-Related Receptors in Diseases of the Female Reproductive System.","authors":"Jinzheng Wang, Ziming Zhu, Liding Fan, Weiyue Zhang, Fangyuan Li, Lin Liu, Letao Jing, Kai Meng, Jinxiang Yuan, Huali Zhang","doi":"10.2174/0118715303406667250915224123","DOIUrl":"10.2174/0118715303406667250915224123","url":null,"abstract":"<p><p>Diseases of the female reproductive system are prevalent. These conditions often have a high proportion of asymptomatic patients and prolonged treatment durations. Estrogen, a crucial steroid hormone, plays a central role in most diseases of the female reproductive system. It is essential for promoting the development of reproductive organs and follicular growth, maintaining regular menstrual cycles, and supporting pregnancy. The expression levels of estrogen-related receptors and circulating estrogen are closely linked to various female reproductive disorders. However, most diseases of the female reproductive system lack specific therapeutic drugs, and estrogen therapy is still primarily used as monotherapy. The clinical application of hormone-targeted therapies remains immature. In light of these challenges, this review focuses on the effects of estrogen and estrogen-related receptors on common diseases of the female reproductive system. This review provides an overview of the pathogenesis and therapeutic mechanisms of four common gynecological disorders: endometriosis (EMS), abnormal uterine bleeding (AUB), polycystic ovary syndrome (PCOS), and premature ovarian insufficiency (POI). This study aims to identify novel target receptors and provide insights for estrogen-based therapies in the treatment of diseases of the female reproductive system.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303406667"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294880","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":"The Causal Relationship between Antibody Immune Response and Ischemic Stroke: A Mendelian Randomization Analysis.","authors":"Chunshu Rong, Zhen Wei, Yuetong Zhao, Donge Xie, Xu Wang, Dexi Zhao","doi":"10.2174/0118715303471180260716103550","DOIUrl":"10.2174/0118715303471180260716103550","url":null,"abstract":"<p><strong>Introduction: </strong>Recognizing the risk factors associated with Ischemic Stroke (IS) is essential for its prevention. Currently, there are no studies exploring the causal link between antibodymediated immune responses and IS. This Mendelian Randomization (MR) study further examines whether a causal relationship exists between antibody-mediated immune responses and IS, and offers evidence supporting causality.</p><p><strong>Methods: </strong>Data on antibody-mediated immune responses came from 9,724 subjects (European ethnicity) as the research participants and who collected their serum samples for microbiological serological analysis. By employing a multiplex antigen detection technique, the total antibody concentrations against various antigens in the samples were systematically measured. IS data were acquired from the MEGASTROKE consortium, which provides stroke-related summary data based on genome- wide association studies, encompassing 40,585 stroke patients and 406,111 control individuals (European ethnicity). MR analysis was conducted to estimate the associations between antibodymediated immune responses (exposure) and IS (outcome) risk.</p><p><strong>Results: </strong>The inverse variance weighted analysis revealed that 26 antibody-mediated immune responses were associated with IS in three subtypes in genetic prediction. There is an effect of anti- Chlamydia trachomatis, anti-cytomegalovirus, anti-human herpesvirus, <i>Varicella-zoster</i> virus, anti- Merkel cell polyomavirus, Epstein-Barr virus, anti-Helicobacter pylori, anti-JC polyomavirus, and anti-Toxoplasma antibodies on the three subtypes of IS in genetic prediction.</p><p><strong>Discussion: </strong>In large-artery atherosclerosis and small-vessel stroke, a high antibody level may be accompanied by direct endothelial cell invasion and vascular inflammation. In cardioembolic stroke, however, high antibody levels may instead reflect efficient viral latency maintenance with reduced systemic inflammation or hypercoagulability associated with cardiogenic embolism. In addition, different antigenic components (momp A vs. total IgG) against <i>C. pneumoniae</i> showed opposite associations.</p><p><strong>Conclusion: </strong>The research provides new genetic evidence for the complex role of antibody-mediated immune responses in the etiology of stroke, suggesting that pathogen-specific immune responses may serve as differentiated risk markers and potential intervention targets for different subtypes of stroke.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303471180"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687379","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":"Shi Pi Shu Gan Formula Prevents and Treats Sequelae of Pelvic Inflammatory Disease by Regulating PKA-CREB-Yap1 Signaling through the mtDNA/cGAS/STING Network.","authors":"Yuyang Mi, Haiqing He, Yefang Huang, Li Huang, Maoya Li, Xiaoli Ji, Yan Wang","doi":"10.2174/0118715303458984260714211650","DOIUrl":"10.2174/0118715303458984260714211650","url":null,"abstract":"<p><strong>Introduction: </strong>To investigate the effects and mechanisms of Shi Pi Shu Gan formula (SPSGF) on sequelae of pelvic inflammatory disease (SPID) in rats with liver stagnation and spleen deficiency.</p><p><strong>Methods: </strong>A SPID rat model was established using mixed bacterial infection, mechanical injury, and compound stress (restraint, fatigue, diet disorder). Rats were divided into control, model, SPSGF-low (9.9 g/kg), SPSGF-high (36.9 g/kg), positive control, mitophagy inhibitor (Mdivi-1), SPSGF, and SPSGF+Mdivi-1 groups (n=6 each) for a 2-week treatment. Behavior, uterine histopathology (HE, TUNEL, immunohistochemistry), inflammatory cytokines (ELISA), mitophagy (TEM), and cGAS, STING, p-CREB, and p-YAP1 proteins (Western blot) were assessed.</p><p><strong>Results: </strong>SPSGF treatment reduced inflammatory lesions and apoptosis in uterine tissue, decreased mtDNA levels and cGAS/STING expression, and increased p-CREB and p-YAP1 expression compared with the model group.</p><p><strong>Discussion: </strong>This study's findings illuminate a novel link between mitochondrial quality control and tissue repair in SPID. Notwithstanding its limitations, including the model's translational capacity and the formula's complexity, this work lays the groundwork for developing SPSGF as a promising multi-targeted therapeutic strategy, aligning with TCM principles for managing chronic inflammatory sequelae.</p><p><strong>Conclusion: </strong>SPSGF may inhibit the inflammatory response in SPID rats by activating mitophagy to inhibit excessive activation of the cGAS/STING pathway and by activating the downstream PKACREB- Yap1 signaling pathway by interfering with the mtDNA-cGAS-STING network, thereby alleviating the symptoms of SPID.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303458984"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687347","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}