Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Jiawei Duhuo Jisheng Mixture Attenuates H₂O₂-induced Oxidative Injury and Osteogenic Dysfunction in Primary Osteoblasts: An Integrated Target Analysis and Experimental Validation.","authors":"Jin Wu, Fu Shen, Zifeng Ye, Zhi Wen, Min Lu, Guang Xia, Jiyong Yang, Linhua Wang, Bocheng Zou, Binbin Li, Gaoyan Kuang, Xiaotong Xu","doi":"10.2174/0118715303532780261009114612","DOIUrl":"https://doi.org/10.2174/0118715303532780261009114612","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative stress-induced osteoblast dysfunction is an important event in osteoporosis (OP). Jiawei Duhuo Jisheng Mixture (JDJM) is clinically used for bone-related disorders, but its molecular basis in OP remains unclear. This study explored OP-related candidate targets of JDJM and evaluated its cytoprotective effects in a hydrogen peroxide (H2O2)-induced primary osteoblast injury model.</p><p><strong>Methods: </strong>Candidate JDJM targets were predicted from its identified constituents and intersected with OP-related genes. The study integrated network-based and enrichment analyses with single-cell mapping, followed by molecular docking and molecular dynamics simulation. An H2O2-induced primary osteoblast injury model was used for experimental validation.</p><p><strong>Results: </strong>A total of 210 shared targets were identified. Network pharmacology and enrichment analyses implicated JDJM in the regulation of oxidative stress, inflammatory responses, extracellular matrix remodelling, osteogenesis and apoptosis, primarily through the MAPK, JAK-STAT and PI3K-Akt signalling pathways. Single-cell transcriptomic analysis further localized these candidate targets to osteogenic, stromal, vascular, and inflammatory cell populations. Molecular docking and dynamics simulations predicted stable interactions between representative JDJM-derived compounds and selected protein targets. In H2O2-injured primary osteoblasts, JDJM significantly reduced mean DCF fluorescence intensity, increased the alkaline phosphatase (ALP)-positive area and Alizarin Red S absorbance, and partially restored osteocalcin/bone Gla protein (OCN/BGP) protein and Bglap mRNA expression.JDJM was also associated with decreased total JAK1, STAT3, MAPK3, MMP9, and Bad expression and partial restoration of ESR1 expression.</p><p><strong>Discussion: </strong>JDJM attenuated H2O2-induced oxidative injury and osteogenic dysfunction in primary osteoblasts, accompanied by changes in JAK1, STAT3, MAPK3, MMP9, ESR1, and Bad expression. These results support a multi-target cytoprotective effect of JDJM under oxidative-stress conditions, although direct regulation of the corresponding signaling pathways remains to be confirmed.</p><p><strong>Conclusion: </strong>JDJM attenuated H2O2-induced oxidative injury and partially restored osteogenic function in primary osteoblasts, accompanied by coordinated expression changes in JAK1, STAT3, MAPK3, MMP9, ESR1, and Bad. These findings support a multi-target protective effect of JDJM against oxidative stress-related osteoblast dysfunction.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187384","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 of Krüppel-like Factor 14 rs4731702 Polymorphism in Type 2 Diabetes Mellitus.","authors":"Heba Osman Mohamed Eldidamony, Maysaa El Sayed Zaki, Mohamed Anies Rizk, Ahmed Mohsen Faheem, Mostafa Abdelsalam Ramadan","doi":"10.2174/0118715303406864260803042753","DOIUrl":"https://doi.org/10.2174/0118715303406864260803042753","url":null,"abstract":"<p><strong>Background/objective: </strong>Krüppel-Like Factor 14 (KLF14) polymorphism has been investigated as a potential genetic risk factor for type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between KLF14 rs4731702 (C/T) polymorphism and T2DM susceptibility in Egyptians.</p><p><strong>Methods: </strong>A case-control study was conducted on 100 patients with T2DM and 100 healthy controls. Genotyping of KLF14 rs4731702 (C/T) was performed using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Clinical and biochemical parameters were compared among different genotypes.</p><p><strong>Results: </strong>The CT and TT genotypes were significantly more frequent in diabetic patients (40% and 30%, respectively) than in controls (15% and 20%, respectively) (p<0.001). Subjects carrying CT and TT genotypes showed significantly higher fasting blood glucose, HbA1c, total cholesterol, and triglyceride levels than those carrying the CC genotype.</p><p><strong>Discussion: </strong>These findings suggest a possible association between the T allele and metabolic abnormalities associated with T2DM.</p><p><strong>Conclusion: </strong>KLF14 rs4731702 (C/T) polymorphism is significantly associated with susceptibility to T2DM in the Egyptian population. The increased prevalence of CT and TT genotypes, along with their association with hyperglycemia and dyslipidemia, suggests that the T allele may contribute to metabolic disturbances and disease development. Further large-scale studies are needed to confirm these findings and clarify the underlying mechanisms.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187377","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":"Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Reveal the Multi-target Anti-influenza a Virus Potential of Cynanchum Atratum.","authors":"Dan Song, Yadong Li, Tao Zheng, Bin Yang","doi":"10.2174/0118715303493863260929075000","DOIUrl":"https://doi.org/10.2174/0118715303493863260929075000","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Influenza A Virus (IAV) remains a major global health threat due to its high mutability and transmissibility, while drug resistance and dysregulated immune responses limit current therapeutic options. To address these challenges, this study developed a molecular dockingbased screening platform to efficiently identify anti-IAV herbal candidates from Traditional Chinese Medicine (TCM) and further elucidated the pharmacological mechanisms of the selected compounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A standardized herb-compound dataset was first established using the TCMSP. Key IAVrelated targets were then collected through literature mining, followed by structure-based virtual screening of bioactive compounds by molecular docking. On this basis, the source herb was reversetraced and further investigated using network pharmacology, including target intersection analysis, protein-protein interaction network construction, and GO and KEGG enrichment analyses. Molecular docking and Molecular Dynamics (MD) simulations were subsequently performed to evaluate the stability of representative compound-target complexes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Retrospective analysis revealed a strong association between multiple constituents of Cynanchum atratum (CA) and IAV inhibition. Using network pharmacology, we systematically evaluated the therapeutic potential and mechanisms of CA against IAV, identifying 21 key bioactive compounds, 291 potential targets, and 136 shared targets between CA and IAV, with AKT1, IL6, EGFR, and JUN likely serving as core targets. GO and KEGG enrichment analyses showed that the shared targets were mainly associated with the TNF, IL-17, and MAPK signaling pathways, Th17 cell differentiation, and COVID-19-related pathways. Molecular docking showed that the core constituents of CA bound favourably to the key targets, with the strongest binding energies reaching -9.8 kcal/mol against JUN and -9.6 kcal/mol against EGFR. MD simulations further corroborated these docking results, among which the EGFR-ethyl oleate complex exhibited the greatest conformational stability over 100 ns, with a mean RMSD of 0.228 ± 0.028 nm and an MM/PBSA binding free energy of -19.6 kcal/mol.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The convergence of target-network, pathway-enrichment, molecular docking, and MD simulation results indicates that CA may act on multiple IAV-related targets and regulate both viral infection-associated and host inflammatory responses. These findings are consistent with the multicomponent and multi-target pharmacological characteristics of TCM and support the applicability of the integrated computational platform for anti-IAV herbal discovery. Nevertheless, the predicted compound-target interactions and biological mechanisms require further validation in cellular and animal models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study developed a comprehensive computational strategy for discovering TCMs against IAV, a","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170705","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 Analysis of T-cell Exhaustion Genes in Pediatric Allergic Rhinitis and their Clinical Diagnostic Significance.","authors":"Huihui Niu, Xiangbin Chai, Qinxue Wang","doi":"10.2174/0118715303467104260922061525","DOIUrl":"https://doi.org/10.2174/0118715303467104260922061525","url":null,"abstract":"<p><strong>Background: </strong>Pediatric Allergic Rhinitis (PAR) is a chronic inflammatory condition. TCell Exhaustion (TCE) contributes to immune dysfunction. This study explored TCE-related genes in PAR and constructed a diagnostic model.</p><p><strong>Methods: </strong>Differential expression analysis was performed on GSE19187 data (14 PAR, 11 controls). Intersection with TCE-associated genes yielded TCE-related Differentially Expressed Genes (TCERDEGs). Functional enrichment, logistic regression, the Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO) were applied to build a diagnostic model and identify hub genes. Immune infiltration was also analyzed.</p><p><strong>Results: </strong>Twenty-two TCERDEGs were identified. IFNG and CD96 showed the strongest positive correlation (r = 0.89), while FSTL3 and MTOR showed the strongest negative correlation (r = -0.70). Many TCERDEGs localized to chromosomes 3 and 9. A diagnostic model was established with three hub genes: CD96, CD200R1, and TRAF1. Immune analysis revealed strong positive correlations between activated CD4 memory T cells and resting dendritic cells (r = 1), and negative correlations between resting and activated NK cells (r = -0.78). CD96 positively correlated with naive B cells (r = 0.58), while TRAF1 negatively correlated with resting mast cells (r = -0.57).</p><p><strong>Discussion: </strong>This study developed a PAR diagnostic signature consisting of CD96, CD200R1, and TRAF1 from T‑cell‑exhaustion‑related genes, highlighting the vital role of T‑cell exhaustion‑mediated immune dysregulation in pediatric allergic rhinitis. The distinct correlations between hub genes and multiple infiltrated immune cells further suggested that these biomarkers might contribute to PAR pathogenesis by modulating the local immune microenvironment. Nevertheless, these results are derived from public transcriptomic datasets, and prospective clinical samples are required to verify the diagnostic performance and biological function of the three candidate genes.</p><p><strong>Conclusion: </strong>Aberrant expression of CD96, CD200R1, and TRAF1, linked to immune infiltration, suggests TCE-related immune changes may underlie PAR pathogenesis. These genes show potential as diagnostic biomarkers, though further clinical validation is needed. Our findings provide a useful diagnostic model and insights into PAR immune status.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083647","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":"Exploring the Influence of Demographic and Clinical Parameters on Knowledge, Attitudes, and Practices in Type- II Diabetes Mellitus Patients in Punjab, India: A Cross-Sectional Study","authors":"Sandeep Kaur, Sidharth Mehan, Ghanshyam Das Gupta","doi":"10.2174/0118715303401307251007044510","DOIUrl":"10.2174/0118715303401307251007044510","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus is a global health issue, affecting over 6.2% of the population. Effective management of type II diabetes mellitus (DM II) depends largely on patients' knowledge, attitudes, and practices (KAP). This study has examined how demographic and clinical factors influence KAP among DM II patients in Punjab, India, aiming to identify knowledge gaps and behavioral trends.</p><p><strong>Methods: </strong>A cross-sectional study was conducted from February 2023 to July 2024 across three outpatient clinics in Punjab. A total of 500 patients were recruited using non-probability purposive sampling. Data were collected using a pre-validated questionnaire and analyzed through SPSS software. KAP scores were assessed and categorized into poor, fair, or good, with multiple linear regression used to identify significant predictors.</p><p><strong>Results: </strong>Among the 500 participants (197 females, 303 males), demographic and clinical factors significantly influenced KAP scores (p<0.05). Higher scores were associated with males, married individuals, those with higher educational attainment, health insurance, and regular clinic visits. Education was a key predictor of improved KAP across all domains. Conversely, poor scores were linked to lower education levels, absence of health insurance, and limited physical activity. Gender disparities were observed, with males displaying better knowledge and attitudes, while females exhibited higher practice scores.</p><p><strong>Conclusion: </strong>This study has highlighted disparities in KAP among DM II patients in Punjab, emphasizing the critical role of education, healthcare access, and physical activity. Targeted interventions, community-based educational programs, and policy-driven improvements in healthcare accessibility are essential to bridge knowledge gaps, reshape attitudes, and foster positive practices. These findings can guide the development of tailored strategies for diabetes management, ultimately improving health outcomes and quality of life for affected individuals.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303401307"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357439","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":"Unraveling the Lipidomic Determinants of Atrial Fibrillation: An Extensive Mendelian Randomization Study","authors":"Lingyan Ye, Dongli Lin, Feng Chen, Xiaoyong Huang, Xianjun Wu","doi":"10.2174/0118715303378914250418095928","DOIUrl":"10.2174/0118715303378914250418095928","url":null,"abstract":"<p><strong>Background: </strong>Atrial Fibrillation (AF) is the most prevalent form of cardiac arrhythmia, with a complex etiology that implicates lipid metabolism. This study employs Mendelian Randomization (MR) to dissect the causal relationships between lipidomic profiles and AF, utilizing comprehensive genetic data to clarify these associations.</p><p><strong>Methods: </strong>Summary statistics for 179 lipid species across 13 classes were retrieved from the GWAS Catalog, encompassing 7,174 Finnish individuals from the GeneRISK study. For AF, data were synthesized from six major studies comprising over one million subjects. Our Two-Sample MR (TSMR) approach was implemented using Inverse Variance Weighting (IVW), MR-Egger, and MR-PRESSO for sensitivity analysis. Additionally, we uniquely integrated the Mendelian Randomization-Bayesian Model Averaging (MR_BMA) method to robustly prioritize the most likely causal lipid determinants of AF, and performed bidirectional MR analysis to assess potential reverse causality.</p><p><strong>Results: </strong>The TSMR analysis, reinforced by MR_BMA, revealed significant causal associations between specific lipid species and AF risk. In particular, Phosphatidylcholine (17:0_18:2) was associated with a decreased risk of AF (OR = 0.96, 95% CI 0.93-0.99, P<0.05), whereas Phosphatidylcholine (16:0_20:5) and Phosphatidylcholine (17:0_20:4) were linked to increased risks (OR = 1.04, 95% CI 1.01-1.07, P<0.01; and OR = 1.02, 95% CI 1.00-1.05, P<0.05, respectively). Furthermore, elevated levels of Phosphatidylethanolamine (18:0_20:4) (OR = 1.03, 95% CI 1.01-1.06, P<0.01) and Triacylglycerol (50:4) (OR = 1.04, 95% CI 1.00-1.07, P<0.05) were also associated with increased AF risk. In addition, Sphingomyelin (d34:2), Sterol ester (27:1/18:0), and Sterol ester (27:1/18:3) emerged as further risk factors, thereby expanding the spectrum of lipidomic determinants implicated in AF. The bidirectional MR analysis provided no evidence of reverse causation, reinforcing the directionality of the lipid-driven association. Sensitivity analyses demonstrated robust findings with no indication of pleiotropy or heterogeneity.</p><p><strong>Conclusion: </strong>This study provides strong evidence for the causal role of specific lipid species in the development of AF. Our comprehensive MR analysis not only deepens our understanding of AF pathophysiology but also highlights the therapeutic potential of targeting these lipid alterations. Notably, the absence of reverse causation supports a unidirectional relationship wherein altered lipid species drive AF risk.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303378914"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048436","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":"Metabolomic Analysis of the Effects of Canagliflozin on HFpEF Rats and Its Underlying Mechanism","authors":"Guorui Zhang, Qingjuan Zuo, Sai Ma, Lili He, Zhongli Wang, Jianlong Zhai, Tingting Zhang, Yan Wang, Yifang Guo","doi":"10.2174/0118715303373321250108174111","DOIUrl":"10.2174/0118715303373321250108174111","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) represents a challenging cardiovascular condition characterized by normal systolic function but impaired diastolic performance. Despite its increasing prevalence, therapeutic options remain limited. This study investigated the metabolic effects of canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on cardiac function and energy metabolism in HFpEF.</p><p><strong>Methods: </strong>We established a rat model of HFpEF using Dahl salt-sensitive rats and evaluated three experimental groups: control (A), HFpEF (B), and canagliflozin-treated HFpEF (C). This study carried out comprehensive analyses of cardiac structure and function, metabolomic profiling, and detailed assessment of myocardial energy metabolism, including mitochondrial respiratory capacity and ATP synthesis. Additionally, we validated our findings using H9C2 cardiomyocytes under controlled conditions.</p><p><strong>Results: </strong>Canagliflozin treatment significantly improved cardiac remodeling markers, including reduced myocardial volume and fibrosis area, while enhancing diastolic function (E/A ratio). Metabolomic analysis revealed normalization of hypermetabolic states, with significant reductions in key metabolites, including L-lysine, D-glucose, and uridine. The treatment restored balance in multiple metabolic pathways, particularly affecting β-alanine metabolism, pyrimidine metabolism, and the citrate cycle. Notably, canagliflozin enhanced mitochondrial respiratory function, increased ATP synthesis, and optimized fatty acid utilization, as evidenced by reduced free fatty acid content.</p><p><strong>Conclusion: </strong>Our findings demonstrated that canagliflozin exerts cardioprotective effects through multiple metabolic pathways, suggesting its potential as a therapeutic option for HFpEF. The ability of the drug to optimize energy metabolism and improve mitochondrial function represents a novel mechanism for treating this challenging condition.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303373321"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019450","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":"Single-cell RNA Sequencing Analysis Reveals the Regulatory Functions of Copines Family Genes in Testicular Cancer Progression","authors":"Nan Li, Kai Yu, Delun Huang, Xuehong Zhu, Zhong Lin","doi":"10.2174/0118715303375462250430055914","DOIUrl":"10.2174/0118715303375462250430055914","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;The aim of this study is to investigate the expression patterns and regulatory functions of Copines family genes in different cellular subpopulations in testicular cancer based on single-cell data and to analyze the regulatory mechanism of Copines family genes in cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Testicular cancer is a frequently diagnosed male tumor. Emerging evidence suggests that Copines family genes are implicated in a variety of cancer phenotypes and cancer progression. Analyzing the expression pattern of Copines family genes in testicular cancer may help improve the treatment efficacy of the cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study sought to characterize the expression profiles of Copines family genes in the cellular subpopulations of testicular cancer and to identify key signaling pathways through which they regulate cancer progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Based on single-cell transcriptomic data of testicular cancer, we classified testicular cancer cell subpopulations and analyzed the expressions of Copines family genes in each subpopulation. Cell subpopulations were grouped according to the expression levels of Copines family genes, and differentially expressed Copines family genes between the groups were screened by differential expression analysis. Functional enrichment analysis on the differentially expressed genes (DEGs) was performed with a clusterprofiler package. Functional pathways enriched by the Copines family genes were calculated by AUCell enrichment score. Copy number variation (CNV) analysis was performed using inferCNV to analyze gene mutation patterns across cellular subpopulations, and pseudotime analysis was conducted using Monocle to infer cellular differentiation pathways of cellular subpopulations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Single-cell clustering identified four major cell subpopulations, namely, NK/T cells, tumor cells, B cells, and macrophages. Notably, the control samples had a relatively small proportion of tumor cells. Further clustering of the tumor cells identified six cell subpopulations, among which multiple Copines genes, especially CPNE1 and CPNE3, showed a high expression. The testicular cancer samples were grouped by the expression patterns of Copines genes, and the DEGs between groups included GNLY, MGP1, CFD2, CCL21, SPARCL13 as well as some other genes involved in the malignant progression of cancer. Pseudotime analysis showed that the upregulated genes were enriched in cell migration and PI3K-Akt pathway, while the downregulated genes were related to immunity. This indicated that the Copines genes regulated the cellular heterogeneity and malignant transformation in testicular cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study revealed the potential molecular mechanism through which Copines family genes drove the progression of testicular cancer through regulating PI3K-Akt signaling pathway and cell cycle, providing a new target for t","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303375462"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016351","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":"A Comparative Analysis of COVID-19-Associated and Non-COVID-19-Associated Mucormycosis","authors":"Süheyla Kömür, Aslıhan Candevira, Ayşe Seza İnala, Ferit Kuşcua, Behice Kurtarana, Funda Memişoğlub, İlkay Karaoğlanc, Yeşim Taşovaa","doi":"10.2174/0118715303335275250116055824","DOIUrl":"10.2174/0118715303335275250116055824","url":null,"abstract":"<p><strong>Background: </strong>COVID-19-associated Mucormycosis (CAM) has emerged as a significant complication during the COVID-19 pandemic. However, there is a lack of comprehensive comparative studies with non-COVID-associated mucormycosis (NCM).</p><p><strong>Objective: </strong>This study aims to compare the clinical characteristics, risk factors, and outcomes of CAM and NCM to enhance the understanding and management of these infections, particularly during the COVID-19 pandemic.</p><p><strong>Method: </strong>A retrospective multicenter study was conducted at Cukurova University, Malatya İnönü University, and Gaziantep University. We analyzed and compared cases of CAM and NCM diagnosed between January 2018 and February 2022. Data were collected from the infectious diseases and clinical microbiology departments, including demographic details, underlying conditions, treatment regimens, and outcomes.</p><p><strong>Results: </strong>A total of 38 cases were analyzed, with 21 cases of COVID-19-associated mucormycosis (CAM) and 17 cases of non-COVID-19-associated mucormycosis (NCM). The key findings of the study were as follows: CAM was strongly associated with corticosteroid use (p<0.001) and diabetes (p=0.001), while NCM cases were more frequently linked to malignancy and neutropenia (p<0.05). Clinically, CAM cases had a higher incidence of cavernous sinus involvement and bone destruction (p=0.003) compared to NCM cases. However, there was no significant difference in overall survival between the CAM and NCM groups (p=0.201).</p><p><strong>Conclusion: </strong>The study highlights the critical role of corticosteroid use and diabetes as prominent risk factors for CAM. Timely diagnosis and intervention are essential to prevent severe complications, such as cavernous sinus involvement and bone destruction. These findings emphasize the need for tailored management strategies for CAM in the context of COVID-19, with particular attention to these risk factors.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303335275"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461347","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":"Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress via the TLR4/NF-κB/NLRP3 Pathway","authors":"Meng Wang, Qian Ma, Wenjuan Wang, Jiawei Cun, Heng Wen","doi":"10.2174/0118715303393744250423100211","DOIUrl":"10.2174/0118715303393744250423100211","url":null,"abstract":"<p><strong>Background: </strong>Esketamine has shown promise in mitigating tissue damage caused by ischemia- reperfusion injury, making it a potential therapeutic candidate for acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR-ALI).</p><p><strong>Objective: </strong>This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model.</p><p><strong>Methods: </strong>The effects of esketamine on the LIR-ALI rats model were evaluated through histopathological examination, assessment of pulmonary edema, measurement of MDA and SOD levels, and analysis of inflammatory cytokine levels (IL-1β, etc.) in the bronchoalveolar fluid (BALF) and serum. Western blot analysis was used to assess the expressions of TLR4, NF-κB, and NLRP3. TLR4 agonist, LPS, was used to validate the role of NF-κB/NLRP3 pathway in LIRALI.</p><p><strong>Results: </strong>Esketamine significantly alleviated LIR-induced ALI by reducing pulmonary edema, inflammatory cell infiltration, and oxidative stress. Elevated MDA content and suppressed SOD activity were significantly reversed by esketamine, along with inactivity of the TLR4/NF-κB/NLRP3 pathway. Esketamine treatment reduced inflammatory response in BALF and serum. TLR4 activation by LPS reversed the ameliorative effects of esketamine on LIR-ALI.</p><p><strong>Conclusion: </strong>Esketamine protected against LIR-induced ALI by mitigating oxidative stress and suppressing the TLR4/NF-κB/NLRP3 axis. These findings highlight the potential therapeutic value of esketamine for ALI.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303393744Pages"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036695","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}