Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Shi Pi Shu Gan Formula Prevents and Treats Sequelae of Pelvic Inflammatory Disease by Regulating PKA-CREB-Yap1 Signaling through the mtDNA/cGAS/STING Network.","authors":"Yuyang Mi, Haiqing He, Yefang Huang, Li Huang, Maoya Li, Xiaoli Ji, Yan Wang","doi":"10.2174/0118715303458984260714211650","DOIUrl":"10.2174/0118715303458984260714211650","url":null,"abstract":"<p><strong>Introduction: </strong>To investigate the effects and mechanisms of Shi Pi Shu Gan formula (SPSGF) on sequelae of pelvic inflammatory disease (SPID) in rats with liver stagnation and spleen deficiency.</p><p><strong>Methods: </strong>A SPID rat model was established using mixed bacterial infection, mechanical injury, and compound stress (restraint, fatigue, diet disorder). Rats were divided into control, model, SPSGF-low (9.9 g/kg), SPSGF-high (36.9 g/kg), positive control, mitophagy inhibitor (Mdivi-1), SPSGF, and SPSGF+Mdivi-1 groups (n=6 each) for a 2-week treatment. Behavior, uterine histopathology (HE, TUNEL, immunohistochemistry), inflammatory cytokines (ELISA), mitophagy (TEM), and cGAS, STING, p-CREB, and p-YAP1 proteins (Western blot) were assessed.</p><p><strong>Results: </strong>SPSGF treatment reduced inflammatory lesions and apoptosis in uterine tissue, decreased mtDNA levels and cGAS/STING expression, and increased p-CREB and p-YAP1 expression compared with the model group.</p><p><strong>Discussion: </strong>This study's findings illuminate a novel link between mitochondrial quality control and tissue repair in SPID. Notwithstanding its limitations, including the model's translational capacity and the formula's complexity, this work lays the groundwork for developing SPSGF as a promising multi-targeted therapeutic strategy, aligning with TCM principles for managing chronic inflammatory sequelae.</p><p><strong>Conclusion: </strong>SPSGF may inhibit the inflammatory response in SPID rats by activating mitophagy to inhibit excessive activation of the cGAS/STING pathway and by activating the downstream PKACREB- Yap1 signaling pathway by interfering with the mtDNA-cGAS-STING network, thereby alleviating the symptoms of SPID.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303458984"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Research on Nrf2 in Diabetic Nephropathy (2000-2025): A Comprehensive Data-mining-based Study.","authors":"Jie Lin, Tianle Zeng, Cuiying Liao, Jianyi Lu, Li'e Deng, Jingyi Zhou, Qiang Li, Hanqi Lu","doi":"10.2174/0118715303455042260723115141","DOIUrl":"10.2174/0118715303455042260723115141","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Diabetic Nephropathy (DN) is the main cause of End-Stage Renal Disease (ESRD) worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important molecular target for regulating oxidative stress and inflammation in DN. This study aims to quantitatively map the global research landscape of Nrf2 in diabetic nephropathy using bibliometric methods, identifying key contributors, thematic evolution, and emerging trends with implications for drug target development.</p><p><strong>Methods: </strong>Bibliometric analysis was conducted using the Web of Science Core Collection database. Publications from 2000 to 2025 were systematically examined using the \"bibliometrix\" package in R, CiteSpace, and VOSviewer, with a focus on publication trends, countries and institutions, journal impact, and keyword development.</p><p><strong>Results: </strong>In total, 465 papers from authors affiliated with 647 institutions, spanning 2,413 researchers and 45 nations, have been identified as meeting the inclusion criteria. China leads in publications (TP = 321) and citations (TC = 9603). Jilin University has the most publications (n = 79). The most influential journals are Free Radical Biology and Medicine and Frontiers in Pharmacology. The keyword cluster analysis identified five main research clusters, including: (1) oxidative stress; (2) cellular processes affected by oxidative stress; (3) signalling pathways and fibrosis; (4) diabetic complications; and (5) genetics and signalling mechanisms. The recent burst of keywords such as \"stress\" and \"protects\" highlights the evolving research frontiers.</p><p><strong>Discussion: </strong>This analysis confirms that the main contributors to this field are worthy of attention because of their contributions to major research hotspots. A noteworthy trend is that research has shifted from focusing solely on oxidative stress to encompassing integrated mechanisms such as autophagy, inflammation, and cellular protection.</p><p><strong>Conclusion: </strong>This analysis reveals a thematic shift from oxidative stress to autophagy and inflammation, highlighting evolving opportunities for Nrf2-targeted drug development in DN.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303455042"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889902","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":"Signaling Pathways and Medicinal Properties of Quercitrin: A Review.","authors":"Wenchen Yang, Lei Wen, Yee Xing You, Shirley Gee Hoon Tang, Kok-Yong Chin, Suzana Shahar","doi":"10.2174/0118715303475299260810051534","DOIUrl":"10.2174/0118715303475299260810051534","url":null,"abstract":"<p><strong>Introduction: </strong>Quercitrin (QC) is a dietary flavonoid glycoside with diverse pharmacological activities, yet a review on its cellular signaling mechanisms remains lacking. This review aims to synthesize and rigorously assess existing evidence concerning the modulatory influence of QC on essential signaling pathways and its therapeutic effects.</p><p><strong>Methods: </strong>A literature search was performed using Web of Science, Medline, and Embase databases. The synthesis of 25 original experimental studies evaluating QC as a pure compound with specific effects on signaling pathways was reported.</p><p><strong>Results: </strong>QC potentially inhibited pro-inflammatory signaling pathways, including NF-κB, p38 MAPK, JNK, and Jak/Stat, while activating cytoprotective pathways such as Nrf2 and Wnt/β- catenin. Notably, evidence demonstrated context-dependent bidirectional regulation of PI3K/Akt and ERK signaling, with QC suppressing pathological hyperactivation during inflammation while restoring impaired signaling under oxidative stress, metabolic dysfunction, and tissue injury. These molecular actions contributed to anti-inflammatory, antioxidant, chondroprotective, neuroprotective, metabolic, and anticancer effects.</p><p><strong>Discussion: </strong>Current evidence suggests that QC functions as a context-dependent homeostatic regulator rather than a simple pathway activator or inhibitor. Its ability to differentially modulate signaling networks according to disease context may explain its broad therapeutic potential across multiple pathological conditions.</p><p><strong>Conclusion: </strong>Preclinical evidence supports QC as a multi-target signaling modulator with promising therapeutic potential. However, its clinical translation remains limited by insufficient pharmacokinetic data and the absence of well-designed human studies. Future standardized pharmacokinetic investigations and clinical trials are warranted to establish its efficacy and safety.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303475299"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890023","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 Genetic Link between Irritable Bowel Syndrome and Polycystic Ovary Syndrome: Bidirectional Mendelian Randomization and Machine Learning Approaches","authors":"Ziwei Gao, Zhenglin Mei, Yujun Zhang, Siyao Lv, Jingru Song, Wei Ye","doi":"10.2174/0118715303363459250317084005","DOIUrl":"10.2174/0118715303363459250317084005","url":null,"abstract":"<p><strong>Background: </strong>Research has shown a certain correlation between polycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS). The study aims to determine the directionality and underlying biological processes influencing the relationship between these two disorders.</p><p><strong>Methods: </strong>We explored the causal relationship between IBS and PCOS by conducting a comprehensive bidirectional Mendelian randomization (MR) analysis using five different methods and conducted robustness assessments. We extracted differentially expressed genes from the IBS and PCOS datasets for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Additionally, we developed a protein-protein interaction (PPI) network and applied the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine (SVM) methodologies to pinpoint key diagnostic markers. Diagnostic efficacy was further assessed through Receiver Operating Characteristic (ROC) curve analysis for selected genes. Finally, single-sample gene set enrichment analysis (ssGSEA) was carried out to examine immune cell infiltration in IBS and PCOS.</p><p><strong>Results: </strong>MR analysis identified a causal effect of PCOS on IBS (IVW, OR = 1.034, 95% CI: 1.003-1.065, P = 0.029). Conversely, no relationship between IBS and PCOS was observed in the reverse analysis. Furthermore, integrative bioinformatics and machine learning analyses identified CD14 and CASP1 as key diagnostic biomarkers for both IBS and PCOS, which were significantly associated with immune cell infiltration.</p><p><strong>Conclusion: </strong>MR analysis has demonstrated a significant positive causal relationship between PCOS and IBS, though the reverse causality from IBS to PCOS appeared non-significant. The genes CD14 and CASP1 emerged as potential shared diagnostic markers between these two conditions.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303363459"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063736","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":"A Case Report of Anti-GAD65 Antibody-Positive Autoimmune Encephalitis Associated with Diabetes.","authors":"Xiuping Xuan, Liheng Meng, Lulu Chen, Xuemei Xie, Xinghuan Liang, Yingfen Qin","doi":"10.2174/0118715303405229251028051625","DOIUrl":"10.2174/0118715303405229251028051625","url":null,"abstract":"<p><strong>Background: </strong>Patients with GAD65 antibody-associated autoimmune encephalitis who also have diabetes are usually considered to have type 1 diabetes mellitus (T1DM). However, previous reports often lacked β-cell function assessments, relying solely on anti-GAD65 positivity for diagnosis, which is insufficient for accurate classification.</p><p><strong>Case presentation: </strong>We present a 30-year-old Chinese woman diagnosed with GAD65-associated autoimmune encephalitis, hyperthyroidism, and diabetes. Her peak C-peptide level was 3.99 ng/mL, inconsistent with the β-cell dysfunction typical of classic T1DM. The combination of high GAD65 antibody titers and preserved β-cell function made it challenging to determine her diabetes type.</p><p><strong>Conclusion: </strong>This case suggests that clinicians should pay more attention to assessing and monitoring β-cell function when GAD65-associated autoimmune encephalitis is accompanied by diabetes.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303405229"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145703497","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":"Associations of Mercury Exposure with Serum Sex Steroid Hormones in Children 6-18 Years from NHANES 2013-2016.","authors":"Binwei Qiu, Yan Lin","doi":"10.2174/0118715303396515250912001734","DOIUrl":"10.2174/0118715303396515250912001734","url":null,"abstract":"<p><strong>Introduction: </strong>To examine the relationship between mercury exposure and serum sex steroid hormones among children aged 6-18 years.</p><p><strong>Methods: </strong>Data were collected from the NHANES 2013-2016. A cohort of 2,637 Children with available information on mercury exposure, serum sex steroid hormones, and covariates was enrolled. Generalized linear models were applied to explore the association of mercury exposure with sex steroid hormones. Finally, we adopted the Bayesian kernel machine regression (BKMR) model to investigate the effect of mixture exposure to mercury on hormone levels.</p><p><strong>Results: </strong>Methyl mercury (MeHg) and total mercury (Hg) were associated with all sex steroid hormones except E2 (P <0.05). After adjusting for covariates, MeHg and Hg were related to sex hormone- binding globulin (SHBG) and free androgen index (FAI) (P <0.05). Stratified analysis by sex-puberty revealed a negative relationship between Hg and SHBG, while a positive association of MeHg with FAI in prepubertal girls (P <0.05). Their associations were confirmed by the BKMR model analysis, in which the mixture exposure was positively linked to FAI but inversely related to SHBG, particularly among prepubertal girls.</p><p><strong>Discussion: </strong>These findings suggest that mercury may disrupt sex hormone homeostasis during critical developmental windows. Appropriate measures should be implemented to mitigate the adverse effects of mercury on sex hormones in the young population. However, future longitudinal large-scale studies are required for validation.</p><p><strong>Conclusion: </strong>Exposure to MeHg and Hg is associated with increased FAI levels, but decreased levels of SHBG, which are more pronounced in girls. The heightened susceptibility of prepubertal girls underscores the need for targeted public health interventions, including dietary guidance on seafood consumption and early biomonitoring of mercury levels in high-risk populations, to mitigate potential health impacts.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303396515"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188200","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":"Erchen Decoction Induces Browning Tendency in White Adipose Tissue of Obese Rats <i>via</i> the SP1/SREBP/UCP1 Signaling Pathway.","authors":"Yue Luo, Mengzhen Wang, Donglin Liu, Fengyi Guo, Nan Song, Zhe Jin, Ziyu Liu, Xiao Yang","doi":"10.2174/0118715303415055251209122646","DOIUrl":"10.2174/0118715303415055251209122646","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Obesity is a global metabolic challenge that leads to excessive fat accumulation and adipose tissue dysfunction due to the disruption of the balance between energy intake and consumption. This study focuses on whether Erchen Decoction promotes high-fat diet-induced white fat browning in obese rats through the SP1/SREBP/UCP1 signaling pathway, thereby improving obesity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Male SD rats were fed a high-fat diet to establish an obesity model, and were randomly divided into the High-fat diet (HFD) group, Erchen Decoction low dose, medium dose, high dose groups, and high dose + SP1 inhibitor group. Rats fed a normal diet served as the control group. TC, TG, LDL-C and HDL-C were detected by an automatic biochemical analyzer; the morphology of adipose tissue was observed with HE staining; the expression of SP1, SREBP and UCP1 in adipose tissue was detected with immunofluorescence staining; the mRNA and protein expression levels of SP1, SREBP, UCP1, PPA γ, PGC-1α, p-p65, Fass and ACC in white adipose tissue were detected with Real-time PCR and Western blot respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Each dose group of Erchen Decoction and the HD-SP1i group could effectively improve the body weight, blood lipids, and fat tissue morphology of obese rats. After the intervention of Erchen Decoction and HD-SP1i, the expressions of UCP1 and PGC-1α in rat adipose tissue cells were up-regulated, while the expressions of SP1, SREBP, PPA γ, p-p65, Fass, and ACC were inhibited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Obesity is a significant global health challenge closely linked to metabolic disorders. According to Traditional Chinese Medicine (TCM) theory, it is often understood as stemming from spleen deficiency leading to the accumulation of phlegm-dampness. Erchen Decoction, a classic TCM formula, achieves its therapeutic effects through the synergistic action of its herbal components, which collectively strengthen the spleen, resolve phlegm, and eliminate dampness. This study demonstrates that Erchen Decoction effectively reduces body weight, improves dyslipidemia, and alleviates pathological changes in adipose tissue in obese rats. The findings indicate that the decoction promotes a \"browning\" tendency in white adipose tissue, as evidenced by the upregulation of thermogenic markers UCP1 and PGC-1α, and the downregulation of key lipogenic factors SP1, SREBP, Fas, and ACC. These observations suggest that the anti-obesity effects of Erchen Decoction may be mediated through the modulation of the SP1/SREBP/UCP1 signaling pathway, which induces white adipose tissue browning and suppresses lipogenesis. This study provides novel molecular insights into the anti- obesity mechanism of Erchen Decoction, enriching the evidence base for TCM in the treatment of metabolic diseases. Future research should aim to obtain direct histological evidence of UCP1 expression and the formation of multilocular adipocytes, and f","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303415055"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311046","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":"Mendelian Randomization Analysis of Psoriasis and Multiparameter Renal Function Trajectories.","authors":"Zhihao Huang, Shengxiu Liu","doi":"10.2174/0118715303426134251202143308","DOIUrl":"10.2174/0118715303426134251202143308","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;While observational studies suggest that psoriasis may increase the risk of renal impairment, evidence supporting a causal relationship remains inconclusive. This Mendelian randomization (MR) study systematically investigates the genetic causality between psoriasis and multidimensional renal function trajectories, encompassing both static measures and dynamic progression patterns.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We utilized genetic variants associated with psoriasis identified in a Finnish population- based genome-wide study of 373,338 participants. Using a two-sample MR framework, we examined potential causal relationships across six kidney-related outcomes: (1) estimated glomerular filtration rate (eGFR), (2) albuminuria, (3) chronic kidney disease stages G3-G5 (CKD G3-G5), (4) need for dialysis, (5) accelerated progression to CKD (CKDi25), and (6) rapid deterioration in renal function (Rapid3). To ensure robustness, we applied MR-PRESSO for outlier correction and performed inverse-variance weighted (IVW) analyses under a random-effects model as the primary method, complemented by comprehensive sensitivity analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Genetic liability to psoriasis showed no causal association with any of the following renal outcome: eGFR (β = -0.0005, P = 0.393), albuminuria (OR = 0.992, P = 0.819), CKD G3-G5 (OR = 1.012, P = 0.520), dialysis (OR = 0.940, P = 0.377), CKDi25 (OR = 1.013, P = 0.527), or Rapid3 (OR = 1.005, P = 0.728). No evidence of horizontal pleiotropy was detected.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Although prior observational studies have linked psoriasis to impaired kidney function, these associations are likely confounded by factors, such as nephrotoxic drug use (e.g., cyclosporine), metabolic comorbidities, or medical surveillance bias. In contrast, this MR study focused exclusively on genetic susceptibility to psoriasis, effectively avoiding such confounding factors. Our findings provide robust genetic evidence that psoriasis itself does not causally affect kidney function, as supported by the lack of significant associations across multiple renal endpoints. Moreover, genetic overlap between psoriasis and kidney disease risk appears minimal, reinforcing the notion that psoriasis is not an independent driver of renal damage. Clinically, screening should emphasize traditional risk factors, such as hypertension and diabetes. In psoriasis patients without these risk factors, frequent long-term kidney monitoring lacks a genetic rationale, which could optimize resource utilization and prevent unnecessary interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This MR study found no genetic causality between psoriasis and renal impairment across three domains: static kidney function (eGFR, albuminuria), end-stage damage (CKD G3-G5, dialysis), and dynamic progression (CKDi25, Rapid3). These findings challenge prior observational associations and highlight the importance of considering ps","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303426134"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145857","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":"Investigation of the Mechanism of Action of Liu Miao San in the Treatment of Lipid Metabolism Disorders on the basis of Network Analysis and Dynamic Ultrasound.","authors":"Yu-Jia Xu, Hua Hou, Lin Liu, Fang-Jie Bi","doi":"10.2174/0118715303417569251201075052","DOIUrl":"10.2174/0118715303417569251201075052","url":null,"abstract":"<p><strong>Introduction: </strong>Lipid metabolism disorders are a critical global health issue. Liu Miao San (LMS), a traditional Chinese medicine (TCM) formula, has demonstrated clinical efficacy against these disorders; however, its underlying mechanism remains unclear.</p><p><strong>Methods: </strong>Network analysis was performed to predict LMS targets using the TCMSP and ETCM databases, followed by protein-protein interaction (PPI) network construction and GO/KEGG enrichment analyses. These predictions were validated <i>in vitro</i> using oleic acid-stimulated HepG2 cells by assessing lipid accumulation (Oil Red O staining, TG/TC measurements) and SREBP1/PPARγ localization via immunofluorescence. <i>In vivo</i>, high-fat diet (HFD)-induced rat models were used. Rats underwent dynamic ultrasound assessments, plasma and liver biochemical analyses (TG, TC, LDL-C, HDL-C, ALT, AST, TNF-α, IL-6), H&E staining, and liver immunofluorescence.</p><p><strong>Results: </strong>Network analysis identified SREBP1 and PPARγ as core targets. <i>In vitro</i>, LMS reduced lipid accumulation, decreased TG/TC levels, inhibited SREBP1 nuclear translocation, and promoted PPARγ nuclear translocation. <i>In vivo</i>, LMS alleviated HFD-induced lipid disorders, improved liver histopathology, reduced plasma TG/TC/LDL-C/ALT/AST and hepatic TG/TC/TNF-α/IL-6 levels, and normalized ultrasound parameters (e.g., liver volume and echogenicity). Immunofluorescence further confirmed SREBP1 inhibition and PPARγ activation in liver tissue.</p><p><strong>Discussion: </strong>LMS ameliorates lipid metabolism disorders through a dual regulatory mechanism: suppressing SREBP1 (reducing fatty acid and cholesterol synthesis) and activating PPARγ (promoting cholesterol efflux and exerting anti-inflammatory effects). This multitarget action addresses both hepatic and systemic lipid dysregulation.</p><p><strong>Conclusion: </strong>LMS exerts therapeutic effects via SREBP1/PPARγ modulation, supporting its clinical application in TCM and providing a methodological framework for mechanistic studies of complex herbal formulations.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":"e18715303417569"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145849","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}