Journal of Endocrinological Investigation最新文献

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TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy. TSH通过PI3K/AKT/CREB通路上调CYP4B1,促进心肌肥厚。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-08 DOI: 10.1007/s40618-025-02554-z
Ziqi Han, Qianqian Dong, Xiao Lu, Shanshan Liu, Yanlong Yang, Feifei Shao, Limin Tian
{"title":"TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.","authors":"Ziqi Han, Qianqian Dong, Xiao Lu, Shanshan Liu, Yanlong Yang, Feifei Shao, Limin Tian","doi":"10.1007/s40618-025-02554-z","DOIUrl":"10.1007/s40618-025-02554-z","url":null,"abstract":"<p><strong>Background: </strong>Subclinical hypothyroidism (SCH) is closely associated with heart failure and cardiac hypertrophy, yet the underlying mechanism remains unclear.</p><p><strong>Methods: </strong>Cardiomyocytes treated with thyroid-stimulating hormone (TSH) were used as an in vitro model. Cardiac-specific TSHR knockout mice (CKO) were treated with isoproterenol (ISO) to induce cardiac hypertrophy in vivo. Serum FT4, TSH levels, heart weight, body weight and tibial length of mice were evaluated. Heart function was analyzed by M-mode cardiac ultrasonography. The pathological changes in cardiac tissues were detected by immunohistochemistry, hematoxylin-eosin and WGA staining. mRNA levels of ANP, BNP, α-MHC and β-MHC were evaluated by RT-PCR. Western blot was used to detect pathway related proteins. Besides, the transcriptome sequencing analysis and dual-luciferase reporter assays were used to verify the relevant molecular mechanisms.</p><p><strong>Results: </strong>TSH significantly promotes cardiomyocyte hypertrophy in cardiomyocytes. Meanwhile, cardiac-specific TSHR knockout significantly reduced ISO-induced cardiac hypertrophy. This was demonstrated by reductions in cell sizes, decreased HW/BW and HW/TL ratios, along with improved expression of hypertrophic genes. Further transcriptome sequencing results showed that TSH can significantly promote the expression of CYP4B1 in vitro. And the knockdown of CYP4B1 repressed TSH-induced cardiomyocyte hypertrophy. Further mechanistic studies revealed that TSH regulated the expression of CYP4B1 hypertrophy through the PI3K/AKT/CREB signaling pathway. Subsequently, the dual-luciferase assays demonstrated that CREB promotes the transcription of CYP4B1 by binding to its promoter region.</p><p><strong>Conclusion: </strong>Overall, our findings highlight the direct impact of TSH/TSHR on cardiomyocyte hypertrophy and proposed CYP4B1 as a promising target for mitigating cardiac hypertrophy in SCH patients.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Recovery of hypopituitarism in macroprolactinomas: a comparison of medical vs. surgical treatment. Results from a European multicenter study. 巨泌乳素瘤垂体功能减退的恢复:内科与外科治疗的比较来自欧洲多中心研究的结果。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-04 DOI: 10.1007/s40618-025-02559-8
Mario Detomas, Barbara Altieri, Isabella Nasi-Kordhishti, Alice Ryba, Linus Haberbosch, Francesco Chierigo, Timo Deutschbein, Martin Fassnacht, Pietro Mortini, Joerg Flitsch, Juergen Honegger, Marco Losa
{"title":"Recovery of hypopituitarism in macroprolactinomas: a comparison of medical vs. surgical treatment. Results from a European multicenter study.","authors":"Mario Detomas, Barbara Altieri, Isabella Nasi-Kordhishti, Alice Ryba, Linus Haberbosch, Francesco Chierigo, Timo Deutschbein, Martin Fassnacht, Pietro Mortini, Joerg Flitsch, Juergen Honegger, Marco Losa","doi":"10.1007/s40618-025-02559-8","DOIUrl":"https://doi.org/10.1007/s40618-025-02559-8","url":null,"abstract":"<p><strong>Context: </strong>Macroprolactinomas not only cause hypogonadism, but also other pituitary dysfunctions, like deficiency of adrenocorticotrophic hormone (ACTH) and thyroid-stimulating hormone (TSH). While dopamine agonist treatment shows varying recovery rates of these insufficiencies, surgical outcomes are less studied, and a direct comparison between treatments is lacking.</p><p><strong>Objective: </strong>To evaluate recovery of pituitary dysfunction in medically vs. surgically treated patients with macroprolactinoma.</p><p><strong>Design: </strong>Retrospective multicenter study including 104 patients with macroprolactinoma (44 surgically vs. 60 medically treated) with at least two hormonal deficiencies before treatment.</p><p><strong>Results: </strong>Before surgery, all patients presented with hypogonadotropic hypogonadism, 25 (57%) with ACTH-deficiency, and 32 (73%) with TSH-deficiency. 10 months post-surgery, prolactin normalized in 25 (57%) patients, while 19(43%), 15 (60%) and 10(31%) recovered from hypogonadism, ACTH-deficiency, and TSH-deficiency, respectively. Before medical therapy, hypogonadism was observed in all patients, ACTH-deficiency in 31 (52%), and TSH-deficiency in 50 (83%). After 12 months under dopamine agonists, prolactin levels normalized in 36 (60%) patients, 25(42%) recovered from hypogonadism, 17 (55%) from ACTH-deficiency, and 14(28%) from TSH-deficiency. No significant difference in recovery rates between surgical and medical treatment for hypogonadism (OR 1.633, p = 0.338), ACTH-deficiency (OR 0.462, p = 0.319), or TSH-deficiency (OR 0.584, p = 0.339) was observed. Large initial tumor size was a significant negative predictor of recovery for all hormone deficiencies (always p < 0.05), while prolactin normalization was a predictor of recovery of hypogonadism (p < 0.001).</p><p><strong>Conclusion: </strong>Both surgical and medical treatment allow for hormonal recovery in patients with macroprolactinoma, with no significant advantage for either approach. Initial tumor size and prolactin-normalization are predictors of recovery outcomes.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Correction to: Who and how to screen for endogenous hypercortisolism in a highrisk population: a special issue of the journal of endocrinological investigations. 更正:谁以及如何在高危人群中筛查内源性高皮质醇血症:内分泌学调查杂志特刊。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-03 DOI: 10.1007/s40618-025-02545-0
Filippo Ceccato, Massimo Terzolo, Carla Scaroni
{"title":"Correction to: Who and how to screen for endogenous hypercortisolism in a highrisk population: a special issue of the journal of endocrinological investigations.","authors":"Filippo Ceccato, Massimo Terzolo, Carla Scaroni","doi":"10.1007/s40618-025-02545-0","DOIUrl":"10.1007/s40618-025-02545-0","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Plasticity deficits of Tregs remodeling toward Th1-like and Th17-like Tregs in individuals with type 1 diabetes. 1型糖尿病患者Tregs向th1样和th17样Tregs重塑的可塑性缺陷
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-03 DOI: 10.1007/s40618-025-02557-w
Yao Qin, Yuxiao Li, Yueshu Wang, Qianying Wei, Liuyan Dai, Mei Huang, Yang Chen, Yong Gu, Tao Yang, Mei Zhang
{"title":"Plasticity deficits of Tregs remodeling toward Th1-like and Th17-like Tregs in individuals with type 1 diabetes.","authors":"Yao Qin, Yuxiao Li, Yueshu Wang, Qianying Wei, Liuyan Dai, Mei Huang, Yang Chen, Yong Gu, Tao Yang, Mei Zhang","doi":"10.1007/s40618-025-02557-w","DOIUrl":"https://doi.org/10.1007/s40618-025-02557-w","url":null,"abstract":"<p><strong>Purpose: </strong>To identify distinct Th-like regulatory T cell (Treg) subsets in the peripheral blood of individuals with type 1 diabetes (T1D) and investigate potential factors that affect Treg polarization within the context of autoimmunity.</p><p><strong>Methods: </strong>A total of 49 T1D patients and 20 healthy controls (HCs) were enrolled in this study. Th-like Treg subsets, including Th1-like, Th2-like and Th17-like Tregs, as well as Th cell subsets in peripheral blood were assessed by flow cytometry. Single nucleotide polymorphisms in Treg-related genes were analyzed. The levels of inflammatory cytokines were measured by ELISA.</p><p><strong>Results: </strong>We observed a decreased frequency of Th1-like Tregs in peripheral blood of T1D patients, while the proportion of total Foxp3<sup>+</sup> Tregs remained unchanged. Moreover, an imbalance of Th17-like Treg/Th17 cells was noted, characterized by a decreased frequency of Th17-like Tregs and an increased proportion of Th17 cells. Further analysis revealed a correlation between the frequency of Th2-like Tregs and the risk variants of IL-2RA rs3118470. Notably, T1D patients with a normal weight exhibited a higher frequency of Th1-like Tregs compared to their lean and overweight counterparts. However, Treg plasticity was not associated with disease characteristics. Additionally, the serum levels of IL-1β, TNF-α and IL-6 in T1D patients were significantly higher than those in HCs, and the proportions of Th1-like and Th2-like Tregs were negatively associated with IL-6 and TNF-α concentrations in T1D patients, respectively. Nevertheless, the proportions of Th-like Treg subsets in the peripheral blood of HCs exhibited no significant correlation with age, BMI, or the levels of inflammatory cytokines.</p><p><strong>Conclusion: </strong>Our study has provided novel evidence on the altered plasticity and the possible mechanisms underlying the transformation of conventional Tregs towards Th1-like and Th17-like Tregs in the peripheral blood of T1D patients. The findings serve to further augment our understanding of the Treg-mediated immune imbalance that plays a crucial role in the immunopathogenesis of T1D.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The bearded lady Helena Antonia from Liège (1579-1621). 留胡子的夫人海伦娜·安东尼娅(1579-1621)。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2025-01-07 DOI: 10.1007/s40618-024-02525-w
H Valdes-Socin, E Micha
{"title":"The bearded lady Helena Antonia from Liège (1579-1621).","authors":"H Valdes-Socin, E Micha","doi":"10.1007/s40618-024-02525-w","DOIUrl":"10.1007/s40618-024-02525-w","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"783-784"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism. 下丘脑-垂体促甲状腺激素活动的反弹效应:更好地理解甲状腺功能减退症的新模型。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2024-10-21 DOI: 10.1007/s40618-024-02480-6
T Piticchio, C Luongo, P Trimboli, D Salvatore, F Frasca
{"title":"Rebound effect of hypothalamic-pituitary thyreotropic activity: a new model to better understand hypothyroidism.","authors":"T Piticchio, C Luongo, P Trimboli, D Salvatore, F Frasca","doi":"10.1007/s40618-024-02480-6","DOIUrl":"10.1007/s40618-024-02480-6","url":null,"abstract":"<p><strong>Purpose: </strong>Hypothalamic-pituitary thyrotropic activity (HPta) is crucial since TSH is the mainstay for evaluating primary hypothyroidism (hT) and replacement therapy in clinical practice. Despite TSH values, some patients experience symptoms and metabolic alterations, raising several issues about hT. The aim of the study was to investigate factors influencing the TSH values achieved after a period of hT induced in a standardized and controlled manner (TSH_time1).</p><p><strong>Methods: </strong>Our institutional database was searched to extract records of differentiated thyroid cancer (DTC) patients undergoing a LT4 withdrawal protocol prior to radioiodine (RAI) administration. We collected clinical and biochemical parameters before LT4 discontinuation and after one month of induced hT. We performed Mann-Whitney U-test and linear regression analyses.</p><p><strong>Results: </strong>We included 102 patients, with a median age of 44 years. In univariate analyses, TSH_time1 was correlated with age (p 0.005) and the dose pro Kg/die of LT4 assumed until the discontinuation of LT4 (LT4_dose) (p 0.023). The higher the age, the lower the TSH_time1 level. The higher the LT4_dose, the higher the TSH_time1 level. After multivariate analysis, the fittest model included age, BMI, LT4_dose, and systemic inflammation response index with an adjusted R<sup>2</sup> of 0.4.</p><p><strong>Conclusion: </strong>The study highlights new mechanisms that influence HPta. HPta progressively reduces with age, and this must be considered when evaluating TSH values in the elderly. Furthermore, we report for the first time a rebound effect of HPta, determined by the dose pro Kg/die of LT4 taken prior to its discontinuation. Inflammation and metabolic status also affect these phenomena.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"587-596"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Metabolic, genetic and immunological features of relatives of type 1 diabetes patients with elevated insulin resistance. 胰岛素抵抗升高的1型糖尿病患者亲属的代谢、遗传和免疫学特征
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2024-12-10 DOI: 10.1007/s40618-024-02497-x
V Codazzi, V Salvatore, F Ragogna, I Marzinotto, A Anselmo, N Baldoni, M R Pastore, S Martinenghi, A Stabilini, E Bosi, A Giustina, L Piemonti, I Libman, H M Ismail, M J Redondo, V Lampasona, P Monti, A Giovenzana, A Petrelli
{"title":"Metabolic, genetic and immunological features of relatives of type 1 diabetes patients with elevated insulin resistance.","authors":"V Codazzi, V Salvatore, F Ragogna, I Marzinotto, A Anselmo, N Baldoni, M R Pastore, S Martinenghi, A Stabilini, E Bosi, A Giustina, L Piemonti, I Libman, H M Ismail, M J Redondo, V Lampasona, P Monti, A Giovenzana, A Petrelli","doi":"10.1007/s40618-024-02497-x","DOIUrl":"10.1007/s40618-024-02497-x","url":null,"abstract":"<p><strong>Purpose: </strong>Insulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D).</p><p><strong>Objective: </strong>This study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D.</p><p><strong>Methods: </strong>We retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells.</p><p><strong>Results: </strong>While GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass.</p><p><strong>Conclusion: </strong>These findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"765-775"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Anxiety, depression and acromegaly: a systematic review. 焦虑、抑郁与肢端肥大症:系统综述。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2024-11-07 DOI: 10.1007/s40618-024-02483-3
Orlando Silvestro, Trine Lund-Jacobsen, Francesco Ferraù, Elena Sofia Blanca, Antonino Catalano, Giorgio Sparacino, Peter Schwarz, Salvatore Cannavò, Gabriella Martino
{"title":"Anxiety, depression and acromegaly: a systematic review.","authors":"Orlando Silvestro, Trine Lund-Jacobsen, Francesco Ferraù, Elena Sofia Blanca, Antonino Catalano, Giorgio Sparacino, Peter Schwarz, Salvatore Cannavò, Gabriella Martino","doi":"10.1007/s40618-024-02483-3","DOIUrl":"10.1007/s40618-024-02483-3","url":null,"abstract":"<p><strong>Purpose: </strong>scientific literature highlights risk factors linked to the onset of psychopathology in different medical pathological contexts. Acromegaly is a rare condition, particularly noteworthy due to the associated clinical psychological features. This research aimed at understanding the main psychopathological outcomes related to acromegaly, with particular emphasis to anxiety and depression.</p><p><strong>Methods: </strong>In January 2024, in line with PRISMA guidelines, a systematic search based on PubMed, Scopus, Web of Science and PsycInfo was conducted to detect studies considering anxiety, depression and alexithymia in patients suffering from acromegaly. The Keywords used for the search phase were \"Acromegaly\" AND \"Depression\" OR \"Anxiety\" OR \"Alexithymia\".</p><p><strong>Results: </strong>Fifty-five studies were eligible. Anxiety and depression were significantly present in patients with acromegaly, with prevalence rates variable based on disease status and psycho-diagnostic instruments. None of the included studies reported alexithymia in patients with acromegaly. No significant difference was found regarding anxiety and depressive symptoms in patients with acromegaly in comparison with patients suffering from different pituitary diseases and chronic conditions. Anxiety and depression were associated with lower perceived HR-QoL, presence of comorbidity, joint issues, delayed diagnosis, disease duration and body image concerns.</p><p><strong>Conclusions: </strong>Anxiety and depression may be encountered in patients with acromegaly, impacting HR-QoL and the course of the disease. This systematic review suggests that a deeper evaluation of clinical psychological features in patients suffering from acromegaly is needed. Particularly, the early detection of clinical psychological symptoms may lead to multi-integrate interventions promoting individuals' well-being and a better HR-QoL.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"527-546"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
MiR-375: it could be a general biomarker of metabolic changes and inflammation in type 1 diabetes patients and their siblings. MiR-375:它可能是 1 型糖尿病患者及其兄弟姐妹代谢变化和炎症的一般生物标志物。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2024-10-25 DOI: 10.1007/s40618-024-02474-4
Eman A Mostafa, Nagwa Abdallah Ismail, Abeer M Nour El Din Abd El Baky, Tarek F ElShaer, Ingy Ashmawy, Aliaa Ahmed Wahby, Mai Magdy Abdel Wahed, Shereen Hamdy Abd El Aziz
{"title":"MiR-375: it could be a general biomarker of metabolic changes and inflammation in type 1 diabetes patients and their siblings.","authors":"Eman A Mostafa, Nagwa Abdallah Ismail, Abeer M Nour El Din Abd El Baky, Tarek F ElShaer, Ingy Ashmawy, Aliaa Ahmed Wahby, Mai Magdy Abdel Wahed, Shereen Hamdy Abd El Aziz","doi":"10.1007/s40618-024-02474-4","DOIUrl":"10.1007/s40618-024-02474-4","url":null,"abstract":"<p><strong>Purpose: </strong>Type 1 diabetes (T1D) is a chronic autoimmune illness that results in loss of pancreatic beta cells and insulin insufficiency. MicroRNAs (miRNAs) are linked to immune system functions contributing to the pathophysiology of T1D, miRNA-375 is significantly expressed in the human pancreas and its circulatory levels might correspond to beta cell alterations. Pancreatic islet cell antibodies (ICA) and Glutamic acid decarboxylase antibodies (GADA) have roles in autoimmune pathogenesis and are predictive markers of T1D. The aim of this work was to detect serum level changes of miRNA-375, ICA, and GADA in T1D patients, and their siblings compared to healthy controls and correlate them with T1D biochemical parameters.</p><p><strong>Methods: </strong>The study included 66 T1D patients (32 males and 34 females; age range 3-18 years), 22 patients' siblings (13 males and 9 females; age range 4-17 years), and 23 healthy controls (7 males and 16 females; age range 4-17 years). MiRNA-375 levels were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR), while ICA and GADA levels were measured using enzyme-linked immunosorbent assay (ELISA). Data analysis was done utilizing SPSS-17 software.</p><p><strong>Results: </strong>MiR-375 levels were downregulated in T1D patients and further decreased in their siblings when compared to healthy controls. Furthermore, miR-375 exhibited inverse correlations with HbA1c levels but no correlations with Total Insulin Dose, disease duration, or autoantibodies (GADA & ICA).</p><p><strong>Conclusion: </strong>Our study indicates that miR-375 is significantly downregulated in children with T1D and their siblings, suggesting its potential role as a biomarker for beta-cell function and glycemic control.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"757-764"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis. 雌激素通过ERα/KRT19信号轴增强甲状腺乳头状癌的增殖、迁移和侵袭。
IF 5.4 2区 医学
Journal of Endocrinological Investigation Pub Date : 2025-03-01 Epub Date: 2024-10-25 DOI: 10.1007/s40618-024-02473-5
Z M Song, Y D Wang, F Chai, J Zhang, S Lv, J X Wang, Y Xi
{"title":"Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis.","authors":"Z M Song, Y D Wang, F Chai, J Zhang, S Lv, J X Wang, Y Xi","doi":"10.1007/s40618-024-02473-5","DOIUrl":"10.1007/s40618-024-02473-5","url":null,"abstract":"<p><strong>Background: </strong>Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development.</p><p><strong>Methods: </strong>The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING.</p><p><strong>Results: </strong>Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway.</p><p><strong>Conclusions: </strong>Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"653-670"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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