Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"A Predictive Model for Anemia and Coronary Heart Disease Based on Bidirectional Two-Sample Mendelian Randomization and Machine Learning.","authors":"Yan Zhang, Sheng Fan, Pengcheng Ma, Yunhong Xia, Zeping Hu","doi":"10.2174/0118715303427508251007080833","DOIUrl":"10.2174/0118715303427508251007080833","url":null,"abstract":"<p><strong>Introduction: </strong>Anemia has been linked to an increased risk of coronary heart disease (CHD), yet the underlying causal relationship remains unclear. This study aimed to investigate the bidirectional associations between anemia and CHD using a multi-method approach.</p><p><strong>Methods: </strong>Data were obtained from the European FinnGen biobank and the Gene Expression Omnibus (GEO) database. Mendelian Randomization (MR) analysis was performed with instrumental variables (IVs). The study assessed causal robustness using MR methods and sensitivity analysis, followed by differential expression analysis and weighted gene co-expression network analysis (WGCNA) to screen for core genes. Further, machine learning algorithms, such as least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine (SVM) algorithms, were applied to screen for key diagnostic genes. Additionally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and validation was conducted using an in vitro oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell model and western blot experiments.</p><p><strong>Results: </strong>MR analysis revealed a positive causal link among vitamin B12 deficiency anemia, hemolytic anemia, and coronary heart disease, while cardiovascular events appeared to have a negative association with hemolytic anemia. Integrated bioinformatics analysis identified six core genes involved in immune response, inflammation, and lipid metabolism. To improve the accuracy of key gene screening and avoid bias from a single method, this study combined multiple machine learning algorithms for comprehensive analysis, ultimately identifying IFIH1 and APBB2 as potentially valuable diagnostic biomarkers, and revealing affected macrophages, mast cells, and T cells infiltration. In vitro experiments confirmed altered expression of IFIH1 and APBB2 upon ox-LDL treatment, supporting their role in CHD pathogenesis.</p><p><strong>Conclusion: </strong>This study, through the integration of MR, transcriptomics, and machine learning methods, has for the first time revealed the causal role of vitamin B12 deficiency anemia and hemolytic anemia in the occurrence of CHD, and identified IFIH1 and APBB2 as potential biomarkers. This research study has provided a new theoretical basis and research direction for understanding the molecular link between anemia and CHD and for improving clinical early warning systems.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303427508"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145403433","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":"Fortunellin Elevates the AMPK Pathway to Reduce Lipid Deposition and Immune Disorders in Young Non-Alcoholic Fatty Liver Disease Rats","authors":"Nan Ping, Na Qin","doi":"10.2174/0118715303391165250828111133","DOIUrl":"10.2174/0118715303391165250828111133","url":null,"abstract":"<p><strong>Introduction: </strong>Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and seriously threatens children’s health. Fortunellin exerts a protective role in several human diseases, but its function in NAFLD is unclear. This research tried to uncover Fortunellin’s function and mechanism in young NAFLD rats.</p><p><strong>Methods: </strong>A young rat model of NAFLD was established by administering a high-fat diet (HFD). Also, Fortunellin was delivered via intragastric administration. The effects of Fortunellin on NAFLD were assessed through hematoxylin-eosin staining, analysis of serum levels of ALT, AST, TCH, TG, LDL-C, and HDL-C, Oil Red O staining, Western blot, ELISA, and quantitative real-time PCR (qRT-PCR). Additionally, the Fortunellin mechanism in NAFLD was estimated with Western blot, immunofluorescence, Oil Red O staining, and ELISA assays.</p><p><strong>Results: </strong>Functionally, Fortunellin (5 or 10 mg/kg) reduced liver injury in young NAFLD rats, which was mainly associated with the gradual decrease of a liver index, the increased liver tissue score, and the gradually decreased serum levels of ALT and AST. Also, Fortunellin restrained NFALD rat dyslipidemia by lessening TCH, TG, LDL-C serum levels, and increasing HDL-C levels. Furthermore, Fortunellin repressed liver lipid metabolism and immune disorders in young NAFLD rats. Mechanically, Fortunellin enhanced the AMPK activation in young NAFLD rats. Additionally, Fortunellin relieved lipid deposition and immune disorders in young NAFLD rats, while compound C (CC, an AMPK inhibitor) abolished these impacts.</p><p><strong>Discussion: </strong>This study confirmed that Fortunellin alleviated liver injury in young rats with NAFLD, and this might be achieved by activating the AMPK axis. The completion of this study provided a promising drug for the NAFLD treatment.</p><p><strong>Conclusion: </strong>In summary, Fortunellin alleviated lipid deposition and immune disorders in young rats with NAFLD through the activation of AMPK.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303391165"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002410","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":"Mechanisms of Cinnamomi Cortex against Diabetes Mellitus Explored by Network Pharmacology Combined with Molecular Docking and Experimental Validation","authors":"Jianqin Yu, Zijun Song, Lusheng Wang, Hongyu Yang, Hui Fan","doi":"10.2174/0118715303300442240820075910","DOIUrl":"10.2174/0118715303300442240820075910","url":null,"abstract":"<p><strong>Objective: </strong>Cinnamomi cortex (CC), a traditional Chinese herbal medicine, exhibits antidiabetic properties, yet the underlying mechanisms are not fully understood. Our study combined network pharmacology, molecular docking, and experimental validation to elucidate the antidiabetic mechanisms of CC.</p><p><strong>Methods: </strong>Active components of CC and their potential antidiabetic targets were identified through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database. Molecular docking with core targets was performed using Autodock Vina. The efficacy of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the T2DM mouse.</p><p><strong>Results: </strong>Eleven active components and sixty-six potential antidiabetic targets of CC were identified. The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects.</p><p><strong>Conclusion: </strong>CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated inflammation, providing a multi-pathway therapeutic approach.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303300442"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335711","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":"Advances in Sources, Content Determination, and Bioactivity of 20α-Hydroxyprogesterone.","authors":"Liangyun Li, Shujing Yan, Yuexuan Cheng, Chunhong Zhong, Chunli Chen, Xiaoli Gao","doi":"10.2174/0118715303302957250117052100","DOIUrl":"10.2174/0118715303302957250117052100","url":null,"abstract":"<p><p>20α-hydroxyprogesterone [(20S)-20-hydroxypregn-4-en-3-one, 20α-DHP] is one of the endogenous metabolites of progesterone (Pregn-4-ene-3,20-dione, P4) and a steroid hormone. The literature related to 20α-DHP mainly concentrates on the years from the 1950s to 1970s, and a review of 20α-DHP has not been conducted. In this work, the endogenous and exogenous sources of 20α-DHP are introduced, and methods for determining 20α-DHP in biological samples are described. The biological activities of 20α-DHP are summarized in detail, including the maintenance of pregnancy, endometrial protection, regulation of hormone secretion, ovulation promotion, uterine epithelial cell proliferation, antagonism of breast cancer, and as a diagnostic indicator for psoriasis and polycystic ovarian syndrome. Finally, the pharmacokinetic characteristics of 20α- DHP are briefly introduced to provide a reference for the further development and utilization of 20α-DHP.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303302957"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416408","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":"Metformin Alone and in Combinations Alter the Methylation Patterns of <i>ABCG1</i> and <i>TXNIP</i> Loci in Patients of Type 2 Diabetes.","authors":"Shehla Shaheen, Shamim Mushtaq, Zahida Memon, Rubina Ghani, Asher Fawwad, Fatima Jehangir","doi":"10.2174/0118715303389767251009070040","DOIUrl":"10.2174/0118715303389767251009070040","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;DNA methylation, being a predictor of gene-environment interaction, a dynamic and reversible process, and a target of drugs, may help clinicians to step towards precision medicine. Epigenome-wide association studies have linked methylation changes with type 2 diabetes and glycemic control; among such frequently documented differentially methylated loci include TXNIP (Thioredoxin interacting protein) and ABCG1 (ATP-binding cassette Subfamily G Member 1). However, research evaluating the effects of antidiabetic treatment on DNA methylation is quite meager.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The current study aimed to evaluate the pre-and post-treatment methylation status of ABCG1 and TXNIP loci in individuals diagnosed recently with type 2 diabetes (T2Ds).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In this quasi-experimental study, individuals recently diagnosed with T2Ds were recruited from 1st March 2022 to 12th June, 2023 from diabetes OPDS/clinics. We included the participants (total n=75) as groups that were prescribed Metformin (Met)alone (n=25), Metformin and Dipeptidyl Peptidase- 4 inhibitors in combination (Met+DDP4I) (n=25), and Metformin and Sodium-Glucose co-Transporter 2 Inhibitors in combination (Met+SGLT2I) (n=25). The methylation status of TXNIP and ABCG1 for all the study groups were evaluated by methylation-specific qPCR. Paired T-test and ANOVA were applied to compare the pre-and post-treatment methylation status of the study groups. Pearson’s correlation test followed by multiple linear regression analysis was performed to analyze the respective correlations and effect of different independent variables on the outcome of the study i.e., post-treatment methylation percentages of ABCG1 and TXNIP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In all groups, post-treatment ABCG1 methylation was found to be significantly decreased, post-treatment TXNIP methylation displayed a significant increase. In a model of linear regression, among various dependent variables, BMI was observed to significantly influence post treatment ABCG1 methylation in all groups, including Met alone (β=0.788, p=0.002), Met+DDP4I, (β= 0.754, p=0.04) and Met+SGLT2I (β= 0.733, p=0.027). While post-treatment TXNIP methylation was significantly affected by reduction in HbA1c levels in all groups, Met alone (β= -0.999, p &lt;0.001), Met+DDP4I (β= -0.850 p &lt;0.001) and Met+SGLT2I (β= -1.007, p &lt;0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Metformin alone and its combinations with DDP4I and SGLT2I decrease the methylation of ABCG1, while increase the methylation of TXNIP in patients with type 2 diabetes. The post-treatment ABCG1 methylation is associated with a decrease in BMI, whereas the post-treatment TXNIP methylation is associated with a decrease in HbA1c levels. Considering the effects of antidiabetic drugs on the methylation status of aforementioned loci involved in the control of glycemic and metabolic parameters; the results of the current study may pave a pa","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303389767"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373551","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":"Repurposing of Chinese Medicine Extract against Staphylococcus Aureus: Assessing the Antibacterial and Anti-Transfer Activity of Plasmid in Drug-Resistant Bacteria.","authors":"Yanqing Tong, Jian Kang, Qian Wang","doi":"10.2174/0118715303352305250214071027","DOIUrl":"10.2174/0118715303352305250214071027","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is one of the most frequent human infections, which triggers various infectious diseases like soft tissue infection, lethal pneumonia, endocarditis, and bacteremia. The most common pathogen responsible for simple cystitis is E.coli; however, it also causes pneumonia, bacteremia, and abdominal infections, such as spontaneous bacterial peritonitis.</p><p><strong>Objective: </strong>Chinese medicines have been used effectively in the treatment of infectious disorders; thus, this study aimed to investigate the efficiency of Chinese medicine against S. aureus.</p><p><strong>Methods: </strong>An extract of traditional Chinese medicine was prepared using nine compounds: tongcao, talc, red peony root, fennel, guangui, lychee core, dry sunflower, dianthus, and purslane, to evaluate its antibacterial activity against Staphylococcus aureus RN450RF.</p><p><strong>Results: </strong>The minimum inhibitory concentration (MIC) of the Chinese medicine measured by the consecutive double dilution technique was 200g/L. The drug-resistant plasmid was transferred equally well under controlled laboratory conditions with a median conjugation frequency of 1.1x106. The maximum activity of conjugated transfer of resistant drug plasmid of E. coli CP9 (R45) was observed at 2/1 MIC (100 g/L drug concentration), 32h time interval, with a bacterial concentration 108 CFU/ml.</p><p><strong>Conclusion: </strong>These results suggest that the secondary inhibitory concentration (1/2 MIC) of the Chinese medicine solution can promote the combination and transfer of the resistance plasmid of Chinese medicine (R45) between different strains. The drug concentration, binding time, and initial bacterial concentration have different degrees of positive promotion effects on the conjugation and transfer of drug-resistant plasmids. Traditional Chinese medicine might be a potentially huge disease management and infection control resource.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303352305"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671950","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 Profiling Identifies JUNB/SPI1-Driven Inflammatory Programs and Novel Communication Axes in Myeloid Cells of Sepsis","authors":"Liyao Liu, Lin Zhao, Jixiang Tan","doi":"10.2174/0118715303425071250925075308","DOIUrl":"10.2174/0118715303425071250925075308","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a Systemic Inflammatory Response (SIR) caused by invading pathogens. We aimed to characterize infiltrating cells in sepsis and provide novel insight for the treatment of sepsis.</p><p><strong>Materials and methods: </strong>Whole-blood scRNA-seq samples from four septic patients and five healthy subjects were collected from the Gene Expression Omnibus (GEO) database (GSE175453). The Seurat R package was used for quality control and cell clustering by scRNA- seq analysis. Gene set enrichment analysis (GSEA) was performed using the clusterProfiler R package for pathway enrichment analysis. Then, the SCENIC analysis was used to identify key transcriptional regulons, and the CellChat R package was used for cell communication analysis.</p><p><strong>Results: </strong>We mainly obtained 9 cell clusters, including myeloid cells, T cells, dendritic cells, NK T cells, B cells, plasma B cells, megakaryocytes, mast cells and erythrocytes. Notably, myeloid cells, erythrocytes and mast cells had a higher proportion in sepsis patients. Activated IL-17 and p53 pathways supported anti-infection response in myeloid cells, and JUNB and SPI1 mediated multiple inflammatory pathways, including TNF signaling and neutrophil activation. We also identified that the cell interaction mode of myeloid cells, such as MPZL1-MPZL1 and FASL-FAS, may serve as a potential target for an anti-inflammatory response in sepsis treatment.</p><p><strong>Discussions: </strong>The scRNA-seq analysis revealed pro-inflammatory pathways (IL-17, p53) and key regulators (JUNB, SPI1) in septic myeloid cells. Receptor genes (MPZL1 and FAS) mediated cell communication, offering potential biomarkers and targets for sepsis therapy.</p><p><strong>Conclusion: </strong>We characterized the pro-inflammatory immune response pathways, transcriptional regulon and cell interaction modes of myeloid cells in the development of sepsis.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303425071"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331488","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":"Gene-predicted Causal Association of Immune Cell-mediated Plasma Metabolites with Acute Hepatitis B: A Mendelian Randomization Study.","authors":"Size Li, Ting Fang, Wenying Qi, Shihao Zheng, Wei Wang, Fan-E Cheng, HongBo Du, Xiaobin Zao, Xiaoke Li, Yong'an Ye","doi":"10.2174/0118715303431456260424063524","DOIUrl":"10.2174/0118715303431456260424063524","url":null,"abstract":"<p><strong>Introduction: </strong>Acute Hepatitis B (AHB) remains a significant global health challenge, with complex interactions between metabolic and immune responses influencing disease progression. This study aimed to investigate the causal relationships between immune cell-mediated plasma metabolites and acute hepatitis B using Mendelian Randomization (MR) analysis.</p><p><strong>Methods: </strong>A two-sample MR analysis was conducted using genome-wide association study data from the FinnGen consortium (133 AHB cases and 451,214 controls) to examine relationships between 1,400 plasma metabolites and 731 immune cell phenotypes. Inverse variance weighting, MR-Egger regression, and weighted median analyses were employed to assess causal relationships. Mediation analysis was performed to explore the role of immune cells in metabolite-AHB associations.</p><p><strong>Results: </strong>A total of 49 circulating metabolites were identified as being significantly associated with AHB risk, including 32 risk factors (e.g., 4-methylguaiacol sulfate, N-formylmethionine) and 17 protective factors (e.g., indoleacetylglutamine, beta-hydroxyisovalerate). Mediation analysis revealed 12 pairs of immune cell-metabolite relationships significantly associated with AHB. Notably, phenyllactate levels negatively regulated AHB through CD39+ secreting Treg AC (MP=- 4.83%) and B cell AC (MP=-12.1%), while 4-methylguaiacol sulfate levels positively mediated AHB through CD38 on IgD+ CD24- (MP=6.41%) and naive-mature B cells (MP=7.37%).</p><p><strong>Discussion: </strong>The study's findings provide genetic evidence for causal relationships between specific plasma metabolites and acute hepatitis B risk through immune cell-mediated pathways. The identification of phenyllactate as a protective factor via CD39+ regulatory T cells and 4-methylguaiacol sulfate as a risk factor through CD38+ B cells offers insights into the immunometabolic mechanisms underlying AHB pathogenesis.</p><p><strong>Conclusion: </strong>This Mendelian randomization study reveals novel causal associations between plasma metabolites and acute hepatitis B mediated by specific immune cell phenotypes, providing potential biomarkers and therapeutic targets for future hepatitis B management strategies.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303431456"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261187","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":"REV-ERBα as a Transcriptional Regulator Linking Circadian Rhythm, Metabolism, and Inflammation.","authors":"Xuguang Luo, Ximei Cao","doi":"10.2174/0118715303480841260729054543","DOIUrl":"10.2174/0118715303480841260729054543","url":null,"abstract":"<p><p>The nuclear receptor REV-ERBα modulates the expression of genes associated with circadian rhythm, metabolic homeostasis, and inflammation. Previous studies have demonstrated that circadian disruption drives persistent inflammation, which further contributes to multiple chronic inflammatory complications, including muscle wasting. Muscle wasting is a consequence of disruptions in the balance between energy metabolism and anabolic catabolism. Specifically, this review focuses on the regulatory role of REV-ERBα in energy metabolism and inflammation, with the aim of facilitating the development of novel therapeutic approaches for metabolic syndrome and related disorders. The disruption of circadian and metabolic homeostasis is linked to a rising incidence of inflammatory disorders. <i>Rev-erbα</i> may be a promising target for addressing changes in metabolic pathways and inflammation within the circadian rhythm. Clarifying how the circadian clock and <i>Rev-erbα</i> intersect with immune functions is critical for interpreting immune system function and developing new therapeutic approaches for managing inflammatory conditions, such as muscle wasting. In summary, research on the role of REV-ERBα in energy metabolism and inflammation is currently ongoing. It is necessary that highly selective targeted compounds be developed to advance strategies for metabolic and inflammatory diseases.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303480841"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809731","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":"Immune Checkpoint Inhibitor-induced Diabetes Mellitus: A Clinical Case Series.","authors":"Zhenya Ruseva, Radina Dimitrova","doi":"10.2174/0118715303482804260804060220","DOIUrl":"10.2174/0118715303482804260804060220","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs for the treatment of various malignancies by harnessing the immune system to eliminate cancer cells. However, their antitumor efficacy is accompanied by a spectrum of immune-mediated adverse effects, including endocrine disorders. Among them, diabetes mellitus, though rare compared to thyroid dysfunction, is a serious complication due to its abrupt onset and high risk of life-threatening diabetic ketoacidosis.</p><p><strong>Methods: </strong>This article presents several clinical cases of ICI-induced diabetes mellitus with an emphasis on the clinical presentation, biochemical assessment, and the importance of early recognition.</p><p><strong>Results: </strong>Each of the patients in this clinical case series was admitted to the hospital on an emergency basis with significant hyperglycaemia and ketonuria. Given the established insulin deficiency (low C-peptide levels), after stabilization with intravenous insulin and rehydration, they were switched to maintenance therapy with subcutaneous administration of basal and rapid-acting insulin.</p><p><strong>Discussion: </strong>The management of immune-mediated diabetes mellitus requires an individualized approach, considering the rapid progression to insulin dependence, the oncologic status of the patient, and the need for continuation of immunotherapy.</p><p><strong>Conclusion: </strong>Early identification through regular glucose monitoring and rapid insulin initiation are crucial for effective management of ICI-induced diabetes mellitus. Comprehensive care requires close cooperation between oncology and endocrinology teams, individualized follow-up, and lifelong insulin therapy.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"26 ","pages":"e18715303482804"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027499","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}