Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Severe Hypercalcemia Following Pembrolizumab Therapy: A Case Report and A Literature Review.","authors":"Massimiliano Lazzaroni, Francesco Angelini, Rinaldo Guglielmi, Roberto Novizio, Anjali Iadevaia, Aikaterini Andreadi, Enrico Papini","doi":"10.2174/0118715303409910250725043347","DOIUrl":"https://doi.org/10.2174/0118715303409910250725043347","url":null,"abstract":"<p><strong>Introduction/background: </strong>Immune checkpoint inhibitors (ICIs) play a central role in advanced cancer treatment, but they are associated with immune-related adverse events (irAEs) that include two cases of hypercalcemia induced by the programmed death-1 (PD-1) inhibitor, pembrolizumab. We report a unique case of a colon cancer patient treated with pembrolizumab who acutely developed life-threatening hypercalcemia.</p><p><strong>Case presentation: </strong>This case presents a seventy-five-year-old woman suffering from colon adenocarcinoma with liver metastasis undergoing pembrolizumab therapy. Shortly after its second administration, she developed severe hypercalcemia (21 mg/dL) with acute kidney failure. Serum intact parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrP), 25-OH vitamin D, and 1,25-OH vitamin D were suppressed while computerized tomography (CT) imaging ruled out relevant osteolytic or granulomatous lesions. Treatment included hydration, infusion of zoledronic acid, and high-dose glucocorticoids. The patient's serum calcium levels normalized, andher condition improved. Primary hyperparathyroidism, ectopic PTHrP secretion, and ectopic 25(OH) D-1-hydroxylase expression were ruled out by clinical and laboratory data. Notably, experimental models of PD-1/PD-L1 inhibition have demonstrated increased bone resorption. Although the absence of specific bone turnover markers and a recent 18FDG-PET/CT scan partly limits the understanding of the pathophysiological mechanism, immune-mediated osteoclast activation represents a potential pathophysiological mechanism of acute reversible hypercalcemia.</p><p><strong>Conclusion: </strong>The present case is unique due to its early onset, absence of calcitriol and PTHrP elevation, and rapid response to corticosteroids. Serum calcium should be assessed both before each ICI's dose administration and throughout treatment in case of symptoms suspicious for hypercalcemia to prevent the onset and progression of this rare but critical irAE.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777385","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":"Diagnostic Biomarkers and Targeted Drug Prediction for Acute Kidney Injury: A Computational Approach.","authors":"Liuyin Zhou, Lian Pan, Jiayang Gao, Yi Jiang, Tingting Li, Ruoqing Li","doi":"10.2174/0118715303417142250724042300","DOIUrl":"https://doi.org/10.2174/0118715303417142250724042300","url":null,"abstract":"<p><strong>Introduction: </strong>Acute Kidney Injury (AKI) is a clinical syndrome with rapid onset and poor prognosis, and existing diagnostic methods suffer from low sensitivity and delay. To achieve early identification and precise intervention, there is an urgent need to discover new precise biomarkers.</p><p><strong>Methods: </strong>AKI samples were acquired from Gene Expression Omnibus (GEO) database. AKI-related module genes were identified using the \"WGCNA\" package. The \"Limma\" package was used to filter Differentially Expressed Genes (DEGs). Protein interaction networks were constructed by intersecting key modular genes with DEGs, and six algorithms (MCC, MNC, Degree, EPC, Closeness, and Radiality) in the cytoHubba plug-in were combined to screen candidate genes. Diagnostic biomarkers were cross-screened using LASSO regression with Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning algorithm, and their predictive performance was verified by Receiver Operating Characteristic (ROC) analysis. Transcription Factors (TFs) regulatory network was constructed applying Cytoscape 3.8.0. Finally, the prediction and molecular docking analysis of potential target drugs were performed using the DSigDB database and AutoDockTools.</p><p><strong>Results: </strong>A total of 498 key modular genes significantly associated with AKI were screened, and 88 AKI- related DEGs and 18 candidate genes were further identified. Importantly, four biomarkers with high diagnostic value (DDX17, FUBP1, PABPN1, and SF3B1) were screened and validated using dual machine learning algorithms, including LASSO regression and SVM-RFE. The area under the ROC curve (AUC) values for these biomarkers were greater than 0.8, indicating good predictive performance. Moreover, 19 TFs and 17 miRNA of SF3B1, 10 TFs and 58 miRNA of PABPN1, 15 TFs and 60 miRNA of FUBP1, together with 13 TFs and 109 miRNA of DDX17, were screened. Drug prediction and molecular docking analysis revealed that Demecolcine and Testosterone Enanthate stably bind to certain markers.</p><p><strong>Discussion: </strong>Four potential biomarkers closely related to AKI were identified, which may be involved in the occurrence and progression of AKI by regulating key processes such as transcription. The predicted Demecolcine and Testosterone Enanthate may also be involved in the repair of renal injury by regulating key target genes. Although further experimental validation is still needed, these may still provide new intervention strategies for the treatment of AKI.</p><p><strong>Conclusion: </strong>To conclude, four AKI biomarkers with high diagnostic value were screened by integrating multiple computational methods, revealing a new perspective on the molecular mechanism of AKI. The results provided a new theoretical basis for achieving early precision diagnosis and individualized treatment of AKI.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777384","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":"Genetic Prediction of Causal Association Between Celiac Disease and Thyroid Function: A Two-Sample Mendelian Randomized Study.","authors":"Xiaoshun He, Hanxin Lv, Wangjianfei Yu, Jun He, Yuyang Xie, Lihao Zhou, Hua Wu, Lingchuan Guo, Xiaoqin Yang","doi":"10.2174/0118715303364014250713045734","DOIUrl":"https://doi.org/10.2174/0118715303364014250713045734","url":null,"abstract":"<p><strong>Aim: </strong>Observational studies have suggested an association between celiac disease and thyroid dysfunction, but their causal relationship has not yet been established.</p><p><strong>Methods: </strong>Summary statistics for celiac disease were retrieved from the FinnGen Consortium, thyroid hormone and antibody data were obtained from the ThyroidOmics Consortium, and genetic variants associated with hyperthyroidism and hypothyroidism were sourced from the UK Biobank. MR statistical analyses used the inverse variance weighted algorithm, followed by various sensitivity analyses and reliability evaluations.</p><p><strong>Results: </strong>Genetic proxied celiac disease was significantly associated with increased free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) levels and decreased free triiodothyronine (FT3)/FT4 ratio, whereas the causality of this common enteropathy on thyroid stimulating hormone (TSH), FT3, total triiodothyronine (TT3), and TT3/FT4 ratio (and vice versa) is unfounded. Moreover, the findings of MR analysis tend to favor the causality of celiac disease for hyperthyroidism, but not hypothyroidism.</p><p><strong>Conclusion: </strong>By leveraging large GWAS consortia datasets, our MR study indicates that the genetic liability to celiac disease is suggestively detrimental to the homeostasis of FT4 and TPOAb levels and FT3/FT4 ratio. Our findings provide caution regarding the risk of hyperthyroidism but not hypothyroidism for individuals suffering from celiac disease.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mediating Role of Blood Metabolites in the Association between Basal Metabolic Rate and Obstetrical Disorders: A Mendelian Randomization Analysis.","authors":"Yanqiong Gan, Xinlin Tan, Yu Tang, Qi Shi, Hongbo Qi","doi":"10.2174/0118715303400445250718112316","DOIUrl":"https://doi.org/10.2174/0118715303400445250718112316","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies suggest a link between Basal Metabolic Rate (BMR) and obstetrical disorders; however, causality remains unclear. We investigated the causal effects of BMR on 14 obstetric disorders and evaluated the potential mediating effects of blood metabolites in these relationships.</p><p><strong>Methods: </strong>Using Genome-Wide Association Study (GWAS) summary data, we conducted both univariate and multivariable Mendelian Randomization (MVMR) analyses. The primary causal inference was based on Inverse Variance Weighted (IVW), MR-Egger, weighted median, and sensitivity analyses (Cochran's Q, MR-PRESSO). Mediation analysis was employed to quantify the proportion of effects operating through metabolite-regulated pathways.</p><p><strong>Results: </strong>BMR was inversely associated with hyperemesis gravidarum (OR=0.73, 95%CI: 0.59-0.90, P=0.008), Intrahepatic Cholestasis of Pregnancy (ICP) (OR=0.67, 95%CI: 0.56-0.80, P<0.001), poor fetal growth (OR=0.80, 95%CI:0.71-0.90, P=0.001), and preterm delivery (OR=0.78, 95%CI:0.70-0.87, P<0.001). MVMR identified elevated BMR and mannose levels as protective against ICP, with BMR showing a positive correlation with mannose. Mediation analysis revealed that BMR reduced ICP risk partly through increased mannose (OR = 1.38, 95% CI: 1.19-1.59, P = 2.03 × 10^-5), accounting for 29.93% of the effect.</p><p><strong>Discussion: </strong>Elevated BMR significantly reduced risks of intrahepatic cholestasis (HR=0.67), fetal distress (HR=0.80), and preterm birth (HR=0.78), mediated partly by mannose levels. Mendelian randomization established causality, linking metabolic adaptation to improved pregnancy outcomes. However, these findings, based on European genetic data, limit generalizability, and unmeasured confounders may persist despite MR methods.</p><p><strong>Conclusion: </strong>Higher BMR may lower risks of hyperemesis gravidarum, ICP, poor fetal growth, and preterm delivery. Mannose mediates the protective effect of BMR on ICP, highlighting potential metabolic pathways for intervention.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746711","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":"Danshenol A Mediates the Proliferation and Differentiation of Adipocytes in Thyroid-Associated Ophthalmopathy.","authors":"Yuting Chen, Jie Min, Xiali Yu, Haixiang Ni, Yamei Jin","doi":"10.2174/0118715303382831250712200617","DOIUrl":"https://doi.org/10.2174/0118715303382831250712200617","url":null,"abstract":"<p><strong>Introduction: </strong>An increase in the intraorbital adipose tissue is the main pathological feature of thyroid-associated ophthalmopathy (TAO). IGF-1R activates PI3K/AKT signaling and accelerates adipogenesis. Pingmu decoction has been demonstrated to promote orbital adipocyte apoptosis; however, less is reported regarding the action mechanism of Danshenol A (DA), a single active ingredient of <i>Salvia miltiorrhiza</i> (Danshen). Accordingly, this study aimed to investigate the role and association of DA and IGF-1R in the proliferation and lipid accumulation of orbital adipocytes.</p><p><strong>Methods: </strong>Primary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.</p><p><strong>Results: </strong>Orbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.</p><p><strong>Discussion: </strong>This study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.</p><p><strong>Conclusion: </strong>This study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746709","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":"Metabolic Disease Management through Natural Products: A Thorough Exploration.","authors":"Pranav Kumar Prabhakar","doi":"10.2174/0118715303426691250717134755","DOIUrl":"https://doi.org/10.2174/0118715303426691250717134755","url":null,"abstract":"","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710439","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":"NLRP3 Inflammasome: A New Perspective on Revealing Hotspots and Trends in Uric Acid Metabolism Disorders through Bibliometric Analysis.","authors":"Yi Xu, Yu Wang, Chengjin Lu, Zeyu Liu, Zhijian Lin, Xiaomeng Zhang, Bing Zhang","doi":"10.2174/0118715303376897250702230058","DOIUrl":"https://doi.org/10.2174/0118715303376897250702230058","url":null,"abstract":"<p><p>Uric acid metabolism disorders have become major health concerns, primarily causing conditions such as hyperuricemia, uric acid nephropathy, and gout. Recent research has focused on these disorders' underlying pathological mechanisms and pharmacological treatments, emphasizing the role of the NLRP3 inflammasome. This study aims to analyze and summarize the current research status, hotspots, and trends in this field from a new perspective of the NLRP3 inflammasome, providing insights for future research and disease treatment. Based on the Web of Science Core Collection (WoSCC), this study systematically retrieved all publications related to the NLRP3 inflammasome and uric acid metabolism disorders published between 2009 and 2023. A comprehensive statistical analysis and visualization of the gathered data were conducted using VOSviewer, CiteSpace, R-bibliometrix, Microsoft Excel, Scimago Graphica, and Pajek. A total of 585 articles from 250 journals spanning 49 countries/regions worldwide were identified, demonstrating a consistent annual increase in publications. China contributed the largest number of publications, followed by the United States and South Korea. FRONTIERS IN IMMUNOLOGY emerged as the most prolific journal, while ANNALS OF THE RHEUMATIC DISEASES boasted the highest impact factor. The current research hotspots can be broadly categorized into three themes: the molecular mechanisms underlying NLRP3 inflammasome activation, the pathological mechanisms of NLRP3 inflammasome involvement in uric acid metabolism disorders, and the development of therapeutic compounds/ drugs targeting the NLRP3 inflammasome. Furthermore, the safety of drugs targeting NLRP3 inflammasome may emerge as a significant research trend in the future. Over the past 15 years, the crucial role of the NLRP3 inflammasome in uric acid metabolism disorders has attracted considerable attention. In the foreseeable future, the role of the NLRP3 inflammasome in uric acid metabolism disorders will continue to be a research focus. The development and safety of drugs targeting the NLRP3 inflammasome will remain a future research trend.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692944","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":"Associations of Anthropometric Indicators with Bone Mineral Density and the Risk of Bone Fractures and Falls: A Large-Scale Genetic Correlation Study.","authors":"Xiao Hu, Zhao-Xing Gao, Yan-Yu Zhu, Sheng Li, Wen-Wen Ding, Hai-Feng Pan, Peng Wang","doi":"10.2174/0118715303369995250702111723","DOIUrl":"https://doi.org/10.2174/0118715303369995250702111723","url":null,"abstract":"<p><strong>Introduction: </strong>Although observational studies have suggested potential associations between Anthropometric Indicators (AIs), Osteoporosis (OP), and bone fractures, the causal links are still scarce. This study aimed to comprehensively evaluate the causal relationships between five AIs and site- and age-specific Bone Mineral Density (BMD), as well as bone fractures and falls.</p><p><strong>Methods: </strong>Genetic exposure data for AIs and outcome data for BMD, bone fractures, and falls were retrieved from various genetic consortia. Genome-wide associations of Single-Nucleotide Polymorphisms (SNPs) were selected as Instrumental Variables (IVs) to infer causal effects in univariable and multivariable Mendelian Randomization (MR) analyses.</p><p><strong>Results: </strong>The results of primary univariable MR analyses revealed that a per-unit increase in Hip Circumference (HC) was causally associated with a lower risk of bone fractures (Inverse Variance Weighting [IVW] method: OR = 0.80, 95% CI: 0.74, 0.88; P = 1.73×10^-06). After adjusting for Body Mass Index (BMI), smoking, and alcohol consumption, further Multivariable Mendelian Randomization (MVMR) analysis supported the presence of causal effects of HC on the decreased risk of fractures. Nevertheless, no causal associations were found between Neck Circumference (NC), Waist Circumference (WC), Waist-to-Hip Ratio (WHR), or Intracranial Volume (ICV) and site/age-specific BMD or the risk of bone fractures or falls.</p><p><strong>Discussion: </strong>Genetic MR analysis establishes HC as an independent protective factor against fractures, resolving prior observational evidence. Limitations include European ancestry bias.</p><p><strong>Conclusion: </strong>This study reveals an independent causal association between HC and a lower risk of bone fractures, suggesting that an appropriate increase in HC is beneficial for the prevention of OP.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Combination Therapy of Pasireotide LAR Plus Pegvisomant and Cabergoline Relieved Acromegaly-Related Headache in a Female Patient with AIP-Mutated Acromegaly: A Case Report.","authors":"Penelope Giambò, Sabrina Chiloiro, Antonella Giampietro, Pier Paolo Mattogno, Liverana Lauretti, Laura De Marinis, Antonio Bianchi, Francesco Doglietto, Alfredo Pontecorvi","doi":"10.2174/0118715303400381250715180534","DOIUrl":"https://doi.org/10.2174/0118715303400381250715180534","url":null,"abstract":"<p><strong>Introduction: </strong>Acromegaly is a rare condition characterized by excessive exposure to GH and IGF-1 due to a pituitary adenoma in most cases. The disease is associated with numerous symptoms, including headaches, which are frequently difficult to manage.</p><p><strong>Case presentation: </strong>We report the clinical history of an 11-year-old female patient with an AIP mutation and acromegaly, who was unresponsive to treatment with somatostatin receptor ligands and diagnosed with chronic, disabling headaches resistant to multiple treatments, such as indomethacin, cyclooxygenase-2 inhibitors, gabapentin, melatonin, topiramate, galcanezumab, and verapamil. The patient achieved biochemical control of acromegaly with a combination therapy using lanreotide autogel (Lanreotide ATG) and pegvisomant. However, due to persistent and disabling headaches, lanreotide ATG was discontinued, and combination therapy with pasireotide long-acting release (Pasireotide LAR) and pegvisomant was initiated, resulting in the resolution of the headache, with sustained improvement over time.</p><p><strong>Conclusion: </strong>This case report highlights the potential benefits of pasireotide in the treatment of refractory headaches, particularly when combined with pegvisomant.  .</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683970","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":"Identifying AIM2 Circulating Methylation Levels as a Novel Diagnostic Biomarker for Rheumatoid Arthritis Using Targeted DNA Methylation Sequencing.","authors":"Jianan Zhao, Binghen He, Yu Shan, Kai Wei, Ping Jiang, Yiming Shi, Cen Chang, Yixin Zheng, Fuyu Zhao, Yunshen Li, Yuejuan Zheng, Yehua Jin, Xinliang Lv, Mengru Guo","doi":"10.2174/0118715303401357250707080740","DOIUrl":"https://doi.org/10.2174/0118715303401357250707080740","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the association between <i>AIM2</i> cg11003133 DNA methylation and Rheumatoid Arthritis (RA), evaluating its diagnostic potential for RA and subtypes.</p><p><strong>Methods: </strong>MethylTarget™ sequencing targeted <i>AIM2</i> cg11003133 (chr1:159076528-159076740) in RA, Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), gout, Systemic Lupus Erythematosus (SLE), Dermatomyositis (DM), primary Sjögren's Syndrome (SS), and Healthy Controls (HC) patients. Logistic regression, random forest, and XGBoost models were applied, with Spearman's correlation used to assess associations.</p><p><strong>Results: </strong>RA and RF/CCP-positive patients showed significantly higher methylation at cg11003133_79/91 compared to HC and AS (FDR < 0.05), but lower levels compared to DM. Methylation at cg11003133_139 was elevated in RA compared to AS/SS (FDR = 0.04/0.03). Anti- TNF-α non-responders had higher cg11003133_79/91 methylation levels compared to HC/AS non-responders (FDR < 0.05). RF-negative RA patients had higher cg11003133_91 methylation than AS patients who failed anti-TNF-α treatment (FDR < 0.05). Haplotype CCCC correlated positively with CRP (r = 0.14, P = 0.006); TTTT was significantly negatively correlated with erythrocyte sedimentation rate, CRP, and the presence of diabetes (r = -0.18, -0.15, and -0.14; P < 0.001, 0.003, and 0.008, respectively). XGBoost and RF models achieved AUCs of 0.9911 and 0.9975 for RA versus non-RA, and 1 for RF/CCP double-negative versus double-positive RA.</p><p><strong>Discussion: </strong><i>AIM2</i> cg11003133 methylation is strongly linked to RA, aligning with its role in inflammasome activation. While promising for diagnostics, larger validation is needed.</p><p><strong>Conclusions: </strong><i>AIM2</i> cg11003133 methylation may serve as a diagnostic biomarker for RA and subtypes.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677122","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}