Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Integrative Network Pharmacology Prediction of the Mechanisms of Tri-Ka-Tuk: A Traditional Thai Herbal Formula.","authors":"Pariyapat Singthong, Nopparat Songserm, Subramani Paranthaman Balasubramani, Watcharacha Krongkeha, Ananya Dechakhamphu","doi":"10.2174/0118715303374703250429111617","DOIUrl":"https://doi.org/10.2174/0118715303374703250429111617","url":null,"abstract":"<p><strong>Introduction: </strong>Tri-Ka-Tuk, a traditional Thai herbal formula composed of ginger, black pepper, and long pepper, has long been utilized for its therapeutic properties, particularly in promoting digestive health, enhancing metabolism, and reducing inflammation. However, the underlying molecular mechanisms remain poorly understood. This study employs an integrative network pharmacology approach to reveal the bioactive compounds and pathways mediating the formula's therapeutic effects.</p><p><strong>Methods: </strong>Bioactive compounds of Tri-Ka-Tuk were identified through literature review and database searches. Targets were predicted using SwissTargetPrediction, and gene ontology (GO) enrichment analysis was conducted via ShinyGO. Pathway enrichment analysis utilized KEGG databases to map associated signaling pathways. Protein-protein interaction (PPI) networks were constructed using the STITCH database.</p><p><strong>Results: </strong>GO analysis revealed that Tri-Ka-Tuk's targets are enriched in biological processes such as protein autophosphorylation and phosphorylation-dependent signaling. Cellular component enrichment indicated involvement in membrane-associated regions critical for signaling. Molecular function analysis highlighted kinase activity and ATP binding as central mechanisms. Pathway enrichment analysis identified significant pathways, including the AGE-RAGE signaling pathway in diabetic complications, the HIF-1 pathway, and cancer-related pathways. PPI network analysis showed that hub proteins such as VEGFA, CDK1, and MAPK1 play key roles in mediating the formula's effects.</p><p><strong>Conclusion: </strong>The findings suggest that Tri-Ka-Tuk exerts its therapeutic effects by modulating key molecular pathways involved in inflammation, oxidative stress, apoptosis, and metabolism. The integrative network pharmacology approach followed in this research bridges traditional knowledge with modern pharmacological insights, and highlights Tri-Ka-Tuk's potential as a therapeutic agent for managing diabetes, cancer, and metabolic disorders. Experimental validation of these predictions is essential to confirm the efficacy of the formulation and to expand its clinical applications.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188697","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":"Worldwide Prevalence of Dyslipidemia in Diabetes: An Umbrella Overview of the Meta-Analysis Studies.","authors":"Zahra Hashempour, Fataneh Esmaeili, Ozra Tabatabaei-Malazy, Asieh Mosallanejad, Ghodratollah Panahi","doi":"10.2174/0118715303375795250521041740","DOIUrl":"https://doi.org/10.2174/0118715303375795250521041740","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidemia, a modifiable risk factor for Cardiovascular Diseases (CVDs), is prevalent among individuals with Diabetes Mellitus (DM). The coexistence of DM and dyslipidemia exacerbates the burden of CVDs. Given the variability in findings across systematic reviews, this umbrella review aims to assess the prevalence of dyslipidemia among diabetic patients critically.</p><p><strong>Method: </strong>A systematic search was performed across PubMed, Scopus, Web of Science, and Embase databases to identify meta-analyses addressing the prevalence of dyslipidemia in patients with DM. Studies were selected in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analyses that provided data on the prevalence or mean difference of lipid profile components in diabetic patients were included. To evaluate study quality, the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks were applied, ensuring the reliability and consistency of the findings.</p><p><strong>Results: </strong>Eleven meta-analyses with a total sample size ranging from 433 to 354,088 participants were included. The prevalence of overall dyslipidemia varied between 60% and 65.68%. Specific lipid abnormalities were also prevalent: high total cholesterol (34.7-38.6%), elevated triglycerides (43-52.7%), high low-density lipoprotein cholesterol (34.4-41%), and low high-density lipoprotein cholesterol (43.4-50%). Gender differences were insignificant, with a higher prevalence of dyslipidemia among women compared to men, particularly after menopause (19% vs. 18%).</p><p><strong>Conclusion: </strong>Dyslipidemia is highly prevalent among diabetic patients, with significant gender- specific patterns, particularly affecting postmenopausal women. These findings highlight the importance of early screening and targeted management of lipid abnormalities in DM patients to reduce the risk of vascular complications. Furthermore, the quality assessment indicated that most included studies were of low or very low quality, highlighting the need for more robust research in this field.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183511","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":"Management of Steroid-Induced Diabetes: A Review of Herbal Medications and Their Role in Modulating Insulin Signaling Pathways.","authors":"Jitendra Gupta, Neha Verma, Ankita Wal, Krishna Chandra Panda, Vishnu Vandana Yeleti, Bhupendra Singh, Shriya Mahajan, Harsimrat Kandhari, Pranay Wal","doi":"10.2174/0118715303327497241214054628","DOIUrl":"https://doi.org/10.2174/0118715303327497241214054628","url":null,"abstract":"<p><strong>Background: </strong>Steroids are pharmaceuticals that have been extensively used for the treatment of numerous medical ailments. However, they have several negative effects, one of which is hyperglycaemia or Steroid-induced diabetes. It may happen to anybody, with or without a history of diabetes.</p><p><strong>Objective: </strong>The core objective of this review is to elucidate the pathogenesis, clinical risk factors, and significance of different types of herbal medications utilized in managing steroid-induced diabetes among patients undergoing glucocorticoid therapy.</p><p><strong>Methods: </strong>The relevant data was obtained by reading many sources, including review papers from various publications that included keywords like glucocorticoids, hyperglycaemia, steroids, and herbal medications. Additionally, information was gathered from online sources.</p><p><strong>Results: </strong>Steroid-induced diabetes mellitus (SIDM) represents a typical side effect stemming from an uncontrolled elevation of blood glucose level and it is closely related to the long-term damage and dysfunction caused by steroid use. The most commonly used medicinal plants to help manage blood glucose include <i>Anethum graveolens, Gynura procumbens, Inula racemosa, and Gymnema Sylvestre</i>, and the predominant mode of action for many herbal products and secondary metabolites employed in the management of steroid-induced diabetes revolves around modulating insulin signalling pathways.</p><p><strong>Conclusion: </strong>Glucocorticoids may provoke hyperglycaemia by increasing insulin resistance, which increases hepatic gluconeogenesis while decreasing glucose absorption by peripheral tissues including muscle cells and adipocytes. Presently no current optimal treatment for steroid-induced diabetes is available. Herbal medications have been shown to effectively manage blood sugar levels by maintaining a steroid concentration.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145381","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":"Effects of TGMXD-208, a Novel PI3K Inhibitor, on Adjuvant-induced Arthritic Rats by Suppressing PI3K/AKT Signaling Pathway.","authors":"Jiahua Yin, Jiayu Wang, Wenrui Su, Ran Tang, Zhifang Qin, Xiaoyi Jia, Xiaodong Ma, Shuangying Gui","doi":"10.2174/0118715303373717250509063328","DOIUrl":"https://doi.org/10.2174/0118715303373717250509063328","url":null,"abstract":"<p><strong>Background: </strong>The PI3K/AKT signaling pathway is critical for immune cell proliferation, differentiation, survival, and inflammatory cytokine release. TGMXD-208, a novel dual PI3K inhibitor, selectively targets both PI3Kδ and PI3Kγ, positioning it as a potential therapeutic agent for Rheumatoid Arthritis (RA).</p><p><strong>Methods: </strong>This study evaluated ankle joint swelling and arthritis index and employed HE staining, X-ray imaging, and small animal ultrasonography to assess rat joint tissues. Serum antibodies for IL-1β, IL-6, and TNF-α were determined, as well as organ indices for the spleen and thymus. Western blotting and immunohistochemistry were used to measure the expression and phosphorylation of key enzymes in the PI3K/AKT pathway. The study also examined the impact of TGMXD- 208 on hematological parameters and organs.</p><p><strong>Results: </strong>Our investigation found that TGMXD-208 dramatically reduced ankle redness and swelling, as well as the arthritis index, in rats in the model group. Additionally, TGMXD-208 reduced arthralgia, deformity, and synovial hyperplasia of the knee joint and accelerated blood flow signals, vascular opacities, accumulation of inflammatory cells, and cartilage erosion of the rats' ankle joints to varying degrees. TGMXD-208 therapy markedly reduced serum levels of IL-1β, IL-6, and TNF-α compared to the model group. Besides, it also reduced organ indices. Furthermore, TGMXD-208 diminished the protein levels of p-PI3K and p-AKT. However, hematological parameters were not considerably impacted by TGMXD-208, and no appreciable aberrant alterations were noted in the organs.</p><p><strong>Conclusion: </strong>TGMXD-208 cuts down arthritic symptoms in AA rats by blocking the PI3K/AKT pathway, making it a potential treatment option for RA.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145380","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":"Sterile Inflammation and Cell Death Pathways in Liver Ischemia-Reperfusion Injury: A Review and Perspective.","authors":"Weifan Huang, Wanting Meng, Jianan Zhao, Binbin Zhang","doi":"10.2174/0118715303401342250514102731","DOIUrl":"https://doi.org/10.2174/0118715303401342250514102731","url":null,"abstract":"<p><strong>Background: </strong>Hepatic Ischemia-Reperfusion Injury (IRI) is a critical complication in liver transplantation and resection, driven by oxidative stress and sterile inflammation mediated by damage-associated molecular patterns (DAMPs). Current therapeutic challenges arise from interconnected cell death pathways and redundant inflammatory mechanisms.</p><p><strong>Objective: </strong>This review synthesizes mechanistic insights into DAMP signaling and regulated cell death modalities in IRI, aiming to identify translational gaps and propose precision-targeted therapies.</p><p><strong>Methods: </strong>A literature search in PubMed using keywords \"IRI,\" \"DAMPs,\" and cell death modes was conducted without date restrictions. Peer-reviewed studies on human/animal models were included, with qualitative synthesis of DAMP-cell death interactions.</p><p><strong>Results: </strong>During ischemia, mitochondrial dysfunction releases HMGB1, ATP, and mtDNA, activating Kupffer cell TLR4/RAGE and cGAS-STING pathways, triggering NLRP3 inflammasome-- driven cytokine storms. Reperfusion amplifies ROS bursts, lipid peroxidation, and iron overload, creating a self-sustaining cycle of damage. Cell death modalities exhibit spatiotemporal specificity: hepatocyte ferroptosis dominates early injury, while macrophage pyroptosis and necroptosis predominate in steatotic livers during late phases. HMGB1 lactylation and mtDNA-cGAS signaling emerge as key regulators. Machine perfusion (e.g., hypothermic oxygenated perfusion) reduces biliary complications via mitochondrial resuscitation, outperforming conventional drugbased therapies.</p><p><strong>Conclusion: </strong>Current single-pathway targeting shows limited efficacy due to IRI's complexity. Future strategies should integrate temporal targeting (ferroptosis inhibitors pre-reperfusion; pyroptosis blockers post-reperfusion), DAMP-neutralizing agents (anti-HMGB1 antibodies), and precision preservation combining multi-omics biomarkers with ex vivo pharmacological preconditioning. Addressing metabolic vulnerabilities in fatty livers and refining cell death-specific interventions are critical for bridging translational gaps.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112120","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":"Immunocytes Play a Crucial Role as Mediators in the Protective Effects of D-β-Hydroxybutyrate Dehydrogenase 1 against Type 2 Diabetes Mellitus: A Mendelian Randomization Study.","authors":"Yi-Ying Liu, Yue-Yang Zhang, Qin Wan","doi":"10.2174/0118715303380282250225071730","DOIUrl":"https://doi.org/10.2174/0118715303380282250225071730","url":null,"abstract":"<p><strong>Background: </strong>Observational studies suggest an association between the immune system and type 2 diabetes. The present study sought to ascertain the causal relationship between BDH1 and type 2 diabetes and investigate whether immunocytes mediate this relationship.</p><p><strong>Methods: </strong>Appropriate single nucleotide polymorphisms (SNPs) were carefully selected from publicly available GWAS databases based on rigorous criteria to ensure the validity of the Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary approach for assessing effect sizes, supplemented by four sensitivity analysis techniques: weighted median, simple mode, weighted mode, and MR-Egger regression tests, all aimed at ensuring the robustness and reliability of the IVW results. Reverse MR was conducted to confirm the feasibility of the mediation analysis. Lastly, Cochran's Q test, MR Egger intercept regression, and MR-PRESSO analysis were utilized to examine heterogeneity and horizontal pleiotropy.</p><p><strong>Results: </strong>The expression of BDH1 is inversely associated with the risk of type 2 diabetes, with an odds ratio of 0.97 (95% CI: 0.95-0.99). IgD+ CD38+ B cell absolute count (20.7%), HLA DR on dendritic cell (18.7%), BAFF-R on CD20- CD38- B cell (9.5%), CD25 on IgD+ CD24+ B cell (4.1%), and BAFF-R on IgD+ B cell (3.4%), all exhibit certain mediating effects, whereas IgD+ CD38+ B cell absolute count, activated and resting CD4 regulatory T cell %, CD4+ T cell, transitional B cell absolute count, CD28- CD8 dim T cell absolute count, CD45 on HLA DR+ CD8+ T cell, FSC-A on HLA DR+ natural killer, and SSC-A on plasmacytoid dendritic cell exert masking effects.</p><p><strong>Conclusion: </strong>The findings indicate that immunocytes could serve as a crucial mediating mechanism through which BDH1 exerts its protective effect against type 2 diabetes, offering novel insights for the prevention and therapeutic management of the disease.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113314","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":"Determination of Nitrogen Metabolism-Related Prognostic Signatures for Forecasting Bladder Cancer Prognosis.","authors":"Hongtao Cheng, Yuhong Li, Shuyu Shen","doi":"10.2174/0118715303371907250514054016","DOIUrl":"https://doi.org/10.2174/0118715303371907250514054016","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer is one of the major health threats worldwide, and aberrant regulation of nitrogen metabolism is closely related to its development. Understanding the role of nitrogen metabolism-related genes in BC is pivotal for the development of new therapeutic strategies and prognostic assessment.</p><p><strong>Aim and objectives: </strong>This study aimed to explore the prognostic factors associated with nitrogen metabolism in bladder cancer (BC) and to construct a prognostic model.</p><p><strong>Methods: </strong>Differential expression gene analysis was performed to identify genes associated with nitrogen metabolism by analyzing mRNA expression data from BC patients. The prognostic relationship between these genes and BC patients was analyzed using univariate Cox regression. One hundred one combinatorial machine learning methods were applied for feature selection, and key prognostic genes were identified based on the method with the highest combined score. Immunocyte infiltration analysis was carried out to assess the tumor microenvironmental characteristics of patients in different risk groups.</p><p><strong>Results: </strong>Twenty-five genes significantly associated with prognosis were identified from nitrogen metabolism-related genes. Twenty-three most prognostically predictive signature genes were screened under feature screening with multiple machine-learning models. Immune cell infiltration analysis showed that patients in the high-risk group had significantly different immune cell infiltration, suggesting that these genes may influence BC progression by regulating immune escape mechanisms. These results provide new biomarkers and potential therapeutic targets for precision treatment and prognostic assessment of BC.</p><p><strong>Conclusion: </strong>The expression patterns of nitrogen metabolism-related genes identified can be used as effective biomarkers for bladder cancer prognosis, providing a scientific basis for personalized treatment. Future studies can further explore the specific biological functions and mechanisms of action of these genes to promote more effective clinical applications.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103381","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":"Study on Immune Characteristics and Gene Polymorphisms of Hypertension Patients.","authors":"Xin Wei, Zhongxin Wang, Yigui Tang, Lu Tian, Yuanhong Xu, Meijuan Zheng","doi":"10.2174/0118715303365110250209092351","DOIUrl":"https://doi.org/10.2174/0118715303365110250209092351","url":null,"abstract":"<p><strong>Objective: </strong>Hypertension seriously endangers the health of patients. We studied the immune characteristics and gene polymorphisms of hypertension patients.</p><p><strong>Methods: </strong>Forty-six hypertension patients (including 19 isolated hypertension patients without other diseases (IHP) and 27 complicated hypertension patients with related complications (CHP) and 28 healthy individuals (HCs) were recruited in this study. Immune cells and cytokines were detected by flow cytometry, immunoglobulins (Ig) were detected by immunoturbidimetry, and hormones were detected by chemiluminescence. Besides, gene polymorphisms were detected by PCR.</p><p><strong>Results: </strong>Compared with HCs, the frequency and counts of circulating B cells increased significantly, while CD56dim natural killer (NK) cells decreased significantly in hypertension patients. The frequency and counts of circulating double positive T (DPT) cells increased significantly in IHP patients, while double negative T (DNT) cells decreased significantly in CHP patients as compared with HCs. Hormones and cytokines expression in hypertension patients increased significantly as compared with HCs. B cells were positively correlated with ACTH expression and strongly associated with hypertension. However, high ACTH levels can inhibit IgM expression in CHP patients. Besides, some CHP patients had gene polymorphisms in statins and antihypertensive drug metabolism, which may require individualized adjustments to drug use.</p><p><strong>Conclusion: </strong>This study found the immune characteristics and gene polymorphisms of hypertension patients, which may provide new ideas and a theoretical basis for the prevention and treatment of hypertension.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103384","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":"Association between Serum Osteocalcin and Cardiometabolic Risk Factors in Latent Autoimmune Diabetes in Adults: Insights from Glutamic Acid Decarboxylase Subgroup Analysis.","authors":"Xiuli Fu, Zihui Xu, Jinlin Xu, Qin Tan, Zhongjing Wang","doi":"10.2174/0118715303364381250428100830","DOIUrl":"https://doi.org/10.2174/0118715303364381250428100830","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the association between serum osteocalcin and cardiometabolic risk factors in latent autoimmune diabetes in adults (LADA).</p><p><strong>Background: </strong>Patients with LADA tend to experience poorer glycaemic control, placing them at a higher risk of cardiovascular disease.</p><p><strong>Objective: </strong>This study aimed to explore the relationship between osteocalcin levels and cardiometabolic risk factors, such as HbA1c, lipids, insulin resistance and obesity, in patients with LADA.</p><p><strong>Method: </strong>This retrospective study included 110 patients suffering from LADA with high glutamic acid decarboxylase (GAD) levels (≥180 IU/ml) and 286 with low GAD levels (<180 IU/ml) between January 2018 and December 2021. All participants were aged ≥30 years. Blood samples, collected after 8 hours of fasting, were analysed for osteocalcin and other biomarkers using chemiluminescence immunoassay. Logistic regression analysis assessed the relationship between osteocalcin and cardiometabolic risk factors.</p><p><strong>Results: </strong>The LADA^high group had a lower body mass index (19.5 vs 23.4 kg/m², p = 0.014) and a lower proportion of obesity (19.1% vs 25.2%, p = 0.001) compared with the LADA^low group. Participants in the LADA^high group were slightly older (58.7 vs 58.3 years, p = 0.641). Fasting blood glucose was higher (8.9 vs 8.4 mmol/l, p = 0.068), and C-peptide was lower (1.0 vs 1.8 ng/ml, p = 0.024). Osteocalcin levels were significantly lower in the LADA^high group (12.19 vs 13.96 ng/ml, p = 0.004). Subgroup analyses revealed significant correlations, such as those between osteocalcin and HbA1c in the LADA^low group and an inverse relationship with triglyceride in men from the LADA^high group. Logistic regression analysis indicated that lower osteocalcin levels were significantly associated with a higher risk of poor glycaemic control and increased obesity.</p><p><strong>Conclusion: </strong>Lower osteocalcin levels in patients with LADA with high GAD are associated with worse cardiometabolic parameters and increased cardiovascular risk. Osteocalcin may be a potential marker for assessing cardiometabolic risk in patients with LADA.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083128","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":"EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation Response.","authors":"Cheng Yuan, Qiuyuan Zhou, Feng Chen, Xueyun Gao, Ayinigaer Yusufu, Xiaoyan Wu, Lihua Ni","doi":"10.2174/0118715303366454250507042518","DOIUrl":"https://doi.org/10.2174/0118715303366454250507042518","url":null,"abstract":"<p><strong>Background: </strong>EphrinB2 is known to play a variety of roles in the pathological process of fibrosis in the heart, skin, and retina, according to current research. However, the role of Ephrin- B2 in renal fibrosis remains to be clarified.</p><p><strong>Objective: </strong>We aimed to investigate the role of EphrinB2 in the renal fibrosis model and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Unilateral ureteral obstruction (UUO) models and TGF-β-treated renal tubular epithelial cells (HK2) were adopted in this study to determine if EphrinB2 could lead to renal fibrosis.</p><p><strong>Results: </strong>EphrinB2 was highly expressed in renal tubular cells in UUO mice. Using adeno-associated virus (AAV)-mediated EphrinB2 overexpression, we observed significant improvements in renal function and injury, as well as a marked reduction in fibrosis. For example, EphrinB2 overexpression decreased the expression of fibrosis markers such as Fibronectin and α-SMA by approximately 40%. In vitro, EphrinB2 also significantly reduced extracellular matrix (ECM) deposition and cellular fibrosis under TGF-β stimulation. Mechanistically, EphrinB2 inhibited TGF-β/Smad3 signaling by approximately 40%, and reduced inflammatory markers such as MCP1 and IL-1β by approximately 60% and 35%, respectively.</p><p><strong>Conclusions: </strong>This study uncovered a previously unrecognized anti-fibrotic role of EphrinB2 in renal fibrosis, which is achieved through the prevention TGF-β/Smad3 signaling and inflammation response. It seemed that EphrinB2 might be a promising therapeutic target in the treatment of fibrotic diseases and kidney failure.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039613","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}