Endocrine Connections最新文献

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Validation of preoperative BRAF V600E testing by ThyroSCAN PanelChip in thyroid nodules. 甲状腺扫描面板芯片在甲状腺结节术前BRAF V600E检测的验证。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-16 Print Date: 2025-05-01 DOI: 10.1530/EC-24-0718
Po-Sheng Lee, Jui-Yu Chen, Chia-Chin Lee, Li-Hsin Pan, Jen-Fan Hang, Po-Chung Kuo, Shan-Fan Yao, Chii-Min Hwu, Chin-Sung Kuo
{"title":"Validation of preoperative BRAF V600E testing by ThyroSCAN PanelChip in thyroid nodules.","authors":"Po-Sheng Lee, Jui-Yu Chen, Chia-Chin Lee, Li-Hsin Pan, Jen-Fan Hang, Po-Chung Kuo, Shan-Fan Yao, Chii-Min Hwu, Chin-Sung Kuo","doi":"10.1530/EC-24-0718","DOIUrl":"10.1530/EC-24-0718","url":null,"abstract":"<p><strong>Objectives: </strong>The high cost of preoperative molecular testing remains a significant barrier to their widespread clinical use. This prospective study aims to investigate the clinical applicability of the ThyroSCAN PanelChip, a qPCR-based method, for preoperative BRAF V600E testing in thyroid nodules.</p><p><strong>Materials and methods: </strong>Adult patients undergoing fine-needle aspiration cytology in outpatient settings between April 2023 and June 2024 were enrolled, and molecular testing was performed on aspiration samples. For patients who proceeded to thyroidectomy, postoperative histopathological findings were compared with preoperative cytology and molecular results. Immunohistochemical VE1 staining on pathology specimens served as the gold standard to validate accuracy. A best-estimate approach was also employed to expand the evaluation, including presumed BRAF V600E-negative cases, such as RAS-positive specimens and benign lesions.</p><p><strong>Results: </strong>Among 73 patients who underwent thyroidectomy and were included in the analysis, preoperative molecular testing identified BRAF mutations in 22 patients, detected the wild-type gene in 39 and classified 12 as inaccessible due to insufficient DNA extraction. For the 38 patients with both preoperative genetic results and VE1 staining, performance metrics were: positive predictive value = 95.5%, negative predictive value = 75.0%, accuracy = 86.8%, sensitivity = 84.0% and specificity = 92.3%. Under the best-estimate approach, metrics improved to positive predictive value = 95.5%, negative predictive value = 89.5%, accuracy = 91.7%, sensitivity = 84.0% and specificity = 97.1%.</p><p><strong>Conclusion: </strong>These findings demonstrate that ThyroSCAN PanelChip effectively identifies BRAF V600E mutations in thyroid nodules using residual thyrocytes from fine-needle aspiration samples.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alterations of brain white matter network topological properties in overt hypothyroidism. 显性甲状腺功能减退患者脑白质网络拓扑特性的改变。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-16 Print Date: 2025-05-01 DOI: 10.1530/EC-25-0039
Jinghe Tian, Quan Zou, Jiancang Cao, Liting Wang, Jing Tian, Chen Yang, Wenxiu Ma, Gang Huang, Jian Tan, Wenwen Zhang, Lianping Zhao
{"title":"Alterations of brain white matter network topological properties in overt hypothyroidism.","authors":"Jinghe Tian, Quan Zou, Jiancang Cao, Liting Wang, Jing Tian, Chen Yang, Wenxiu Ma, Gang Huang, Jian Tan, Wenwen Zhang, Lianping Zhao","doi":"10.1530/EC-25-0039","DOIUrl":"10.1530/EC-25-0039","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined the topological properties of brain white matter networks in overt hypothyroidism (OH) patients and their links to cognitive and emotional dysfunction.</p><p><strong>Materials and methods: </strong>Fifty OH patients and 92 healthy controls underwent brain magnetic resonance imaging, clinical assessments and neuropsychological evaluations. Graph-theoretical network analysis based on diffusion tensor imaging was used to calculate global and local topological properties. Between-group differences were analyzed, and partial correlation and mediation analyses were conducted to explore relationships among topological metrics, clinical variables and neuropsychological scores.</p><p><strong>Results: </strong>The OH group showed significantly higher depressive and anxious scores, and lower cognitive scores. In the global topological analysis, the OH group showed decreased global efficiency, which was negatively correlated with the Hamilton Rating Scale for Depression-24 scores. Local topological abnormalities were predominantly observed in the nodal efficiency (NE), degree centrality and nodal local efficiency of several regions within the limbic system and default mode networks. Notably, NE in the left amygdala and left paracentral lobule was negatively correlated with the Hamilton Rating Scale for Depression-24 scores, and decreased NE in the right median cingulate and paracingulate gyri was positively correlated with executive function/visuospatial ability scores and the clock drawing test score.</p><p><strong>Conclusion: </strong>OH patients show depression, anxiety and cognitive impairments linked to global efficiency and regional abnormalities in the limbic system and default mode network. These findings provide insights into the neuropathophysiological mechanisms underlying emotional and cognitive impairments.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association between the AST/ALT ratio and osteopenia or osteoporosis in patients with type 2 diabetes mellitus. 2型糖尿病患者AST/ALT比值与骨质疏松或骨质减少的关系
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-13 Print Date: 2025-05-01 DOI: 10.1530/EC-25-0086
Yuan Zhang, Guanhua Chen, Shanshan Lv, Weimin Wang, Yali Jing
{"title":"The association between the AST/ALT ratio and osteopenia or osteoporosis in patients with type 2 diabetes mellitus.","authors":"Yuan Zhang, Guanhua Chen, Shanshan Lv, Weimin Wang, Yali Jing","doi":"10.1530/EC-25-0086","DOIUrl":"10.1530/EC-25-0086","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to investigate the relationship between the AST/ALT ratio and osteopenia or osteoporosis in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>A total of 589 patients with T2DM were divided into two groups based on T-score: T-score ≥ -1.0 group, normal bone mineral density and T-score < -1.0 group, osteopenia or osteoporosis (OP). The association between the AST/ALT ratio and osteopenia/OP was evaluated by multivariate analyses. The receiver operating characteristic (ROC) curves were used to estimate the diagnostic performance according to the area under the ROC curve (AUC).</p><p><strong>Results: </strong>The patients in the T-score < -1.0 group showed significantly higher AST/ALT level than those in the T-score ≥ -1.0 group (0.93 ± 0.16 vs 1.17 ± 0.24, P < 0.001). According to the interquartile range of the AST/ALT ratio, the participants were divided into four groups: Q1 (0.650, 0.874), Q2 (0.875, 0.999), Q3 (1.000, 1.173) and Q4 (1.174, 1.917). After adjustment for confounding factors, compared with Q1 of the AST/ALT level, subjects in Q3 and Q4 remained more likely to have osteopenia or osteoporosis (Q3, OR 3.478, 95% CI 1.641-7.411; Q4, OR 15.278, 95% CI 6.377-36.837). The AST/ALT ratio provided an AUC value of 0.81 (95% CI 0.77-0.84) for osteopenia or osteoporosis in patients with T2DM.</p><p><strong>Conclusion: </strong>An elevated AST/ALT ratio is associated with the evaluated risk of osteopenia/OP in patients with T2DM. The AST/ALT ratio, a practical and cost-effective biomarker, may be a potential predictor of osteopenia/OP in patients with T2DM.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in clinical features of adrenal Cushing syndrome: a national registry study. 肾上腺库欣综合征临床特征的变化:一项国家登记研究。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-12 Print Date: 2025-05-01 DOI: 10.1530/EC-24-0684
Takuyuki Katabami, Shiko Asai, Ren Matsuba, Masakatsu Sone, Shoichiro Izawa, Takamasa Ichijo, Mika Tsuiki, Shintaro Okamura, Takanobu Yoshimoto, Michio Otsuki, Yoshiyu Takeda, Mitsuhide Naruse, Akiyo Tanabe
{"title":"Changes in clinical features of adrenal Cushing syndrome: a national registry study.","authors":"Takuyuki Katabami, Shiko Asai, Ren Matsuba, Masakatsu Sone, Shoichiro Izawa, Takamasa Ichijo, Mika Tsuiki, Shintaro Okamura, Takanobu Yoshimoto, Michio Otsuki, Yoshiyu Takeda, Mitsuhide Naruse, Akiyo Tanabe","doi":"10.1530/EC-24-0684","DOIUrl":"10.1530/EC-24-0684","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Adrenal Cushing syndrome (CS) has been rarely studied in recent years in Japan. This study aimed to investigate clinical characteristics and their changes over time in patients with adrenal CS. We analyzed 101 patients with adrenal CS caused by adenoma, dividing them into two groups based on diagnosis period: December 2011-November 2016 (later group, n = 50) and August 2005-November 2011 (earlier group, n = 51). Differences between the groups and comparisons with previous reports were assessed. Patients with subclinical CS were excluded. Adrenal incidentalomas were the most frequent reason for CS diagnosis (34%). Most patients exhibited few specific cushingoid features (2.5 ± 1.3), with moon faces and central obesity being the most common. Compared to earlier reports, specific cushingoid features were less frequent; nonetheless, no significant differences were observed between the earlier and later groups. All patients had midnight and post-dexamethasone suppression test serum cortisol levels exceeding 5 μg/dL. No significant differences were found between the groups regarding non-specific symptoms, endocrinological findings related to cortisol secretion, cardiometabolic commodities or infections, except for glucose intolerance and bone complications. The prevalence of metabolic disorders other than glucose intolerance and osteoporosis fluctuated over time. Sixteen patients developed cardiovascular diseases or severe infections. In conclusion, adrenal CS became less florid in the 2000s, showed no improvement in the following years, and remained associated with a high complication rate. Further research is needed to establish an early detection model for CS.</p><p><strong>Plain language summary: </strong>Our study found that one-sixth of patients with adrenal Cushing syndrome continued to develop severe complications in this century despite their specific cushingoid features being less pronounced than in the past. Notably, the findings provide clinical insights that may aid in earlier disease diagnosis.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":"14 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Short stature in pre-pubertal children with X-linked hypophosphatemia. x连锁低磷血症的青春期前儿童身材矮小。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-01 DOI: 10.1530/EC-24-0605
Hanting Liang, Wenting Qi, Chenxi Jin, Cong Zhang, Yushuo Wu, Xiaosen Ma, Qianqian Pang, Ruizhi Jiajue, Yue Chi, Wei Liu, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Jiajun Zhao, Weibo Xia
{"title":"Short stature in pre-pubertal children with X-linked hypophosphatemia.","authors":"Hanting Liang, Wenting Qi, Chenxi Jin, Cong Zhang, Yushuo Wu, Xiaosen Ma, Qianqian Pang, Ruizhi Jiajue, Yue Chi, Wei Liu, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Jiajun Zhao, Weibo Xia","doi":"10.1530/EC-24-0605","DOIUrl":"https://doi.org/10.1530/EC-24-0605","url":null,"abstract":"<p><strong>Objective: </strong>Short stature is a characteristic of X-linked hypophosphatemia (XLH). We aim to explore the factors that influence the height of pre-pubertal children with XLH.</p><p><strong>Methods: </strong>Based on a randomized clinical trial of high/low doses of active vitamin D with neutral phosphate treatment for XLH children, we recruited 124 pre-pubertal children with XLH, and 46 participants completed the 24-month follow-up. Participants were separated into the short stature (height Z score<-2) and non-short stature groups (height Z score≥-2). Height, medication history, biochemical parameters, the Thacher rickets severity score (RSS), and bone age were evaluated.</p><p><strong>Results: </strong>At baseline, 50.8% of participants were short stature. The height Z score of males (-2.35±1.18) was significantly inferior to that of females (-1.86±1.03), p=0.014. The height Z score had negative correlations with age when enrolled, initial age of medication, and RSS (β:-0.327~-0.251, p<0.01), but had a positive correlation with calcium-phosphorus product (β:0.213, p=0.015). Compared to the non-short stature group, the proportion of delayed bone age was higher in the short stature group (10.0% vs. 42.9%, p<0.001). At 24-month follow-up, the median height Z score increased from -1.91 to -1.74 (p=0.002), whose improvement had no significant differences between groups of male/female, high/low doses of calcitriol, and non-truncating/truncating variants.</p><p><strong>Conclusion: </strong>In pre-pubertal children with XLH, a higher height Z score has associations with females, early initiation of treatment, better bone mineralization, and milder rachitic lesions. Conventional therapy improves their heights, but the efficacy does not depend on sex, active vitamin D dosage, or variant type.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network insights into childhood obesity: unveiling methylated-differentially expressed genes and pathways through integrative bioinformatics analysis. 儿童肥胖的网络洞察:通过综合生物信息学分析揭示甲基化差异表达基因和途径。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-01 DOI: 10.1530/EC-25-0049
Felipe Mateus Pellenz, Guilherme Coutinho Kullmann Duarte, Giovanna Câmara Giudicelli, Thayne Woycinck Kowalski, Tais Silveira Assmann, Daisy Crispim
{"title":"Network insights into childhood obesity: unveiling methylated-differentially expressed genes and pathways through integrative bioinformatics analysis.","authors":"Felipe Mateus Pellenz, Guilherme Coutinho Kullmann Duarte, Giovanna Câmara Giudicelli, Thayne Woycinck Kowalski, Tais Silveira Assmann, Daisy Crispim","doi":"10.1530/EC-25-0049","DOIUrl":"10.1530/EC-25-0049","url":null,"abstract":"<p><strong>Background: </strong>Childhood obesity, a global epidemic with profound impacts on physical and psychological health, remains a complex challenge with elusive underlying mechanisms. This study aimed to unravel the epigenetic landscape of this disease by identifying methylated-differentially expressed genes (MeDEGs) in childhood obesity through integrated bioinformatics approaches.</p><p><strong>Methods: </strong>Expression profiling (GSE9624) and methylation profiling (GSE25301, GSE27860, and GSE57484) datasets containing data on children with obesity (cases) and eutrophic children (control group) were obtained from the Gene Expression Omnibus (GEO) repository. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between the groups were identified using GEO2R. MeDEGs were identified by superimposing the lists of DEGs and DMGs. The protein-protein interaction (PPI) network was constructed using the STRING database and analyzed using Cytoscape. Topological and modular PPI network analyses were carried out using the CytoHubba and MCODE plugins, respectively. Functional enrichment analyses were performed based on Gene Ontology terms and KEGG pathways.</p><p><strong>Results: </strong>A total of 70 MeDEGs were identified, including 45 hypomethylated-high expression and 25 hypermethylated-low expression genes. The PPI network highlighted three hub-bottleneck genes (CCL5, STAT1, and GATA3) and two functional modules. Overall, the 70 MeDEGs were associated with KEGG pathways related to cellular differentiation, inflammation, chemokine signaling, lipid and glucose metabolism, insulin resistance, and apoptosis.</p><p><strong>Conclusion: </strong>This study, employing integrative bioinformatics approaches, provides insights into the methylation-mediated mechanisms contributing to childhood obesity, advancing our understanding of this multifaceted chronic disease.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist. 新型甲状旁腺激素受体1激动剂eneoparatide的1期临床试验。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-01 DOI: 10.1530/EC-24-0464
Michel Ovize, Soraya Allas, Michael D Culler, Stephane Milano, Taha Ouldrouis, Mark Sumeray, Jeroen V D Wetering de Rooij, Michael Mannstadt
{"title":"Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist.","authors":"Michel Ovize, Soraya Allas, Michael D Culler, Stephane Milano, Taha Ouldrouis, Mark Sumeray, Jeroen V D Wetering de Rooij, Michael Mannstadt","doi":"10.1530/EC-24-0464","DOIUrl":"10.1530/EC-24-0464","url":null,"abstract":"<p><strong>Objective: </strong>this study evaluated the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of eneboparatide (AZP-3601), a novel agonist of the PTH receptor 1 being developed for the treatment of hypoparathyroidism.</p><p><strong>Design: </strong>This was a randomized, double-blind, placebo-controlled study. 104 healthy volunteers were recruited into 7 single ascending dose (SAD) and 5 multiple ascending dose (MAD) cohorts.</p><p><strong>Methods: </strong>PK parameter were time to peak, Cmax, area under the curve (AUC) and half-life. PD parameters included albumin-adjusted serum calcium (sCa), serum phosphorus (sPh), serum endogenous PTH, 24hr-urinary excretion of calcium (24h-uCa), fractional excretion of calcium (FECa) and bone turnover markers (s-CTX and P1NP).</p><p><strong>Results: </strong>there were no serious adverse events (SAE). All adverse events (AE) were of mild to moderate intensity. AUC and Cmax of eneboparatide increased with increasing doses. Time to maximum plasma concentration was 5-20 minutes. SAD showed a dose-dependent increase of sCa and decrease of sPh associated with a reduction of serum endogenous PTH. MAD demonstrated a rapid access to maximal PD effects and maintained levels of sCa throughout the day. Urinary excretion of calcium did not increase as a function of the dose of eneboparatide. P1NP and s-CTX did not change over the treatment period.</p><p><strong>Conclusion: </strong>The PD effects of eneboparatide were prolonged despite the short half-life. These data suggest that eneboparatide may provide sustained control of serum calcium in patients with hypoparathyroidism with once daily dosing. An open-label phase 2 study in patients with hypoparathyroidism has been recently completed and published and a phase 3 study has been initiated.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LncRNA RP11-34D15.2 sponges miR-223 to promote the PGC-1a/Irisin signaling pathway contributes to increased FFA and insulin resistance in obese children. LncRNA RP11-34D15.2利用miR-223促进PGC-1a/Irisin信号通路,有助于肥胖儿童FFA和胰岛素抵抗的增加。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-05-01 DOI: 10.1530/EC-25-0028
Shuang Guo, Mengnan Lu, Yuesheng Liu, Hongai Zhang, Biyao Lian, Yanfeng Xiao, Chunyan Yin
{"title":"LncRNA RP11-34D15.2 sponges miR-223 to promote the PGC-1a/Irisin signaling pathway contributes to increased FFA and insulin resistance in obese children.","authors":"Shuang Guo, Mengnan Lu, Yuesheng Liu, Hongai Zhang, Biyao Lian, Yanfeng Xiao, Chunyan Yin","doi":"10.1530/EC-25-0028","DOIUrl":"https://doi.org/10.1530/EC-25-0028","url":null,"abstract":"<p><strong>Background: </strong>The global surge in pediatric obesity is closely linked to insulin resistance (IR) and type 2 diabetes, where adipose tissue free fatty acid (FFA) overload and mitochondrial dysfunction play pivotal roles. Long non-coding RNAs (lncRNAs) are emerging regulators of metabolic diseases, but their mechanistic contributions to childhood obesity-associated IR remain underexplored.</p><p><strong>Objective: </strong>This study investigates whether lncRNA RP11-34D15.2 modulates FFA-induced IR through the miR-223/PGC-1α/irisin signaling axis in obese children.</p><p><strong>Methods: </strong>We analyzed serum FFA, insulin, irisin, and white adipose tissue (WAT) transcriptomes in 40 obese and 40 normal-weight children. Functional validation included dual-luciferase reporter assays, primary adipocyte models, and high-fat diet (HFD) mice treated with lncRNA-specific shRNA (n=10 per group). Molecular interactions were verified via RNA immunoprecipitation and Western blotting.</p><p><strong>Results: </strong>Obese children exhibited 2.1-fold higher FFA levels and HOMA-IR (P<0.01) but 38% lower serum irisin compared to controls, with irisin inversely correlating with body fat percentage (r=-0.67, P=0.003). LncRNA RP11-34D15.2 was downregulated by 4.3-fold in obese WAT and positively correlated with irisin expression (r=0.603, P=0.018). Mechanistic studies revealed that lncRNA directly binds miR-223 (RIP-seq fold enrichment=5.2, P=0.004), relieving miR-223-mediated suppression of PGC-1α. Overexpressing lncRNA in adipocytes increased PGC-1α (2.8-fold) and irisin (1.9-fold), upregulated mitochondrial genes (CPT-1: 3.1-fold; UCP-1: 2.4-fold, P<0.01), and reduced extracellular FFA by 44%. In HFD mice, lncRNA knockdown exacerbated glucose intolerance (AUC increased 29%, P=0.007), whereas irisin supplementation restored insulin sensitivity (P=0.013).</p><p><strong>Conclusion: </strong>LncRNA RP11-34D15.2 functions as a ceRNA sponging miR-223 to activate PGC-1α/irisin-mediated mitochondrial β-oxidation and FFA clearance, identifying therapeutic targets for childhood obesity.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peripheral blood HIF-1α levels: a study on their predictive ability for early-stage diabetic retinopathy. 外周血HIF-1α水平对早期糖尿病视网膜病变预测能力的研究
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-04-29 Print Date: 2025-05-01 DOI: 10.1530/EC-25-0004
Zhiqiang Su, Lijuan Chen, Meijuan Lu, Jingyi Li, Liping Qiu, Liting Shi
{"title":"Peripheral blood HIF-1α levels: a study on their predictive ability for early-stage diabetic retinopathy.","authors":"Zhiqiang Su, Lijuan Chen, Meijuan Lu, Jingyi Li, Liping Qiu, Liting Shi","doi":"10.1530/EC-25-0004","DOIUrl":"https://doi.org/10.1530/EC-25-0004","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the correlation between the levels of hypoxia-inducible factor-1α (HIF-1α) in the peripheral blood of patients with type 2 diabetes (T2D) and early-stage diabetic retinopathy (DR) and to evaluate its potential as a predictor of early DR.</p><p><strong>Methods: </strong>From November 2021 to December 2023, 70 patients who underwent fundus photography at Zhangzhou Second Hospital were recruited. Based on the results, patients were categorized into a T2D group comprising 25 patients and a DR group comprising 45 patients. In addition, 18 healthy individuals who underwent routine physical examinations during the same period were included as a control group. Serum levels of the HIF-1α protein were measured in all three groups.</p><p><strong>Results: </strong>The results indicated that patients in the early-stage DR group had significantly higher levels of HIF-1α, albumin (Alb), Ca and blood urea nitrogen (BUN) compared to the T2D group (P < 0.05). In addition, patients in the DR group exhibited higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG) and glycated hemoglobin (HbA1C) than the control group (P < 0.05). The incidence rates of DR in groups A, B, C and D were 18.18, 31.82, 59.09 and 95.45%, respectively, with statistically significant differences (P < 0.05). Spearman's correlation analysis revealed significant positive correlations between HIF-1α and age, disease duration (years), systolic blood pressure, Cr, FPG and HbA1c, with a strong positive correlation between HIF-1α and HbA1c (P < 0.05) optimal cutoff value of 2.3855 ng/mL.</p><p><strong>Conclusion: </strong>Increased levels of HIF-1α in peripheral blood are closely linked to the development of DR, suggesting that HIF-1α may act as a potential biomarker for the early detection and prediction of DR risk.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":"14 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of microRNA-139-5p by glucagon-like peptide-1 ameliorates oxidative stress-induced vascular endothelial cell damage via targeting SOD1/GCLc. 胰高血糖素样肽-1抑制microRNA-139-5p通过靶向SOD1/GCLc改善氧化应激诱导的血管内皮细胞损伤。
IF 2.6 3区 医学
Endocrine Connections Pub Date : 2025-04-29 Print Date: 2025-05-01 DOI: 10.1530/EC-25-0022
Jiaqi Zhang, Jiake Mo, Ying Liu, Xubiao Meng, Weian Tang, Lanfang Fu, Jing Xiong, Zhaohui Mo
{"title":"Inhibition of microRNA-139-5p by glucagon-like peptide-1 ameliorates oxidative stress-induced vascular endothelial cell damage via targeting SOD1/GCLc.","authors":"Jiaqi Zhang, Jiake Mo, Ying Liu, Xubiao Meng, Weian Tang, Lanfang Fu, Jing Xiong, Zhaohui Mo","doi":"10.1530/EC-25-0022","DOIUrl":"https://doi.org/10.1530/EC-25-0022","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Oxidative stress is a key driving factor for the progression of vascular disease in diabetes, and is closely related to endothelial dysfunction. The exact mechanism by which glucagon-like peptide-1 (GLP-1) directly protects vascular endothelium by reducing oxidative stress is not yet fully understood. In this study, we investigated the protective effect of GLP-1 on endothelial cells exposed to palmitic acid (PA)/high glucose-induced oxidative stress and further explored the potential mechanisms involved in microRNA-139-5p (miR-139-5p) regulation. We found that miR-139-5p expression was exhibited significantly elevated in HUVECs that were exposed to PA/high glucose or H2O2, which were reversed by glutathione. Interestingly, this expression was significantly attenuated after GLP-1 pretreatment, with reduced reactive oxygen species (ROS), increased GSH/GSSG ratio and amelioration of cell dysfunction. Overexpression of miR-139-5p resulted in increased ROS and apoptosis, decreased GSH/GSSG ratio, damaged migration and proliferation of HUVECs, while inhibition of miR-139-5p significantly restored PA-induced HUVECs impairments. Further investigation revealed that miR-139-5p directly targets superoxide dismutase 1 (SOD1)/glutamate-cysteine ligase catalytic (GCLc) subunit. The upregulation of miR-139-5p abrogated the protective effects of GLP-1 on cells exposed to PA, and GLP-1-induced downregulation of miR-139-5p was counteracted by the GLP-1 receptor antagonist exendin(9-39). These findings demonstrated that GLP-1 ameliorates oxidative stress-induced endothelial dysfunction, at least in part, by suppressing miR-139-5p, which targets SOD1 and GCLc. This provides further evidence for the vascular protective effects of GLP-1 intervention in diabetes.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":"14 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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