Journal of Endocrinological Investigation最新文献

{"title":"Exploring the interplay of karyotype, hormones, sexuality, and body image perception in individuals with Turner syndrome.","authors":"Chiara Tarantino, Ludovica Vincenzi, Francesco Angelini, Alessandra Tomaselli, Francesco Carlomagno, Elena Rosato, Riccardo Pofi, Andrea Lenzi, Carlotta Pozza, Marianna Minnetti, Matteo Spaziani, Andrea M Isidori, Emilia Sbardella","doi":"10.1007/s40618-024-02521-0","DOIUrl":"10.1007/s40618-024-02521-0","url":null,"abstract":"<p><strong>Purpose: </strong>Most patients with Turner Syndrome (TS) require Hormone Replacement Therapy (HRT). Androgen levels could be compromised due to both ovarian insufficiency and HRT. Despite this, the association between androgen deficiency, sexual health, and body image perception remains underexplored in these patients. This study aimed to assess hormone levels, sexual function, and body image perception in women with TS, categorized by karyotype and HRT regimen.</p><p><strong>Methods: </strong>A cross-sectional analysis of 29 patients with TS was performed. Clinical, hormonal, and ultrasonographic pelvic parameters were evaluated. Sexual function and body image perception were measured using the Female Sexual Function Index (FSFI) and the Body Uneasiness Test (BUT) questionnaires.</p><p><strong>Results: </strong>The cohort included individuals with X chromosome monosomy (Group A), structural X chromosome alterations in some cell lines (Group B) or in all cell lines (Group C), and cells with 46, XX karyotype and monosomy (Group D). Group A and B compared to Group D displayed lower calculated free testosterone (p = 0.006, p = 0.032) and free androgen index levels (p = 0.007, p = 0.025). DHEA-S values differed between groups A and D (p = 0.043) and between groups A and C (p = 0.044). Sexual activity was reported by approximately half of patients (51.7%), with 57% of them presenting sexual dysfunction. Additionally, 44.8% exhibited possible body image disorder.</p><p><strong>Conclusions: </strong>This study acknowledges significant phenotypic differences linked to karyotype in women with TS, highlighting the prevalence of sexual dysfunction and body image dissatisfaction. These findings emphasize the importance of addressing sexual health and body image issues in patients with rare diseases, often neglected in clinical practice.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1225-1236"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411312","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}

{"title":"Male osteoporosis: the impact of lifestyle, from nutrition to physical activity.","authors":"Giuseppe Defeudis, Ludovica Cardinali, Samaneh Eftekhariranjbar, Maria Chiara Massari, Silvia Migliaccio","doi":"10.1007/s40618-024-02517-w","DOIUrl":"10.1007/s40618-024-02517-w","url":null,"abstract":"<p><p>Male osteoporosis is an increasing worldwide pathological condition, characterized by an increased risk of fragility fractures, that is underestimated, underdiagnosed and undertreated. Prevention and treatment play a pivotal role in reducing fractures, and it is important to remember that therapeutic interventions include balanced nutrition and physical activity. Pharmacological treatments are the main and most effective tool to achieve numerous and decisive benefits in this population. Among these, testosterone replacement therapy, when allowed by circumstances and comorbidities, is useful. Anyway, the main goal is always to start from lifestyle, including nutrition and physical activity, plays a very important and crucial role. The many pieces of this puzzle, called lifestyle, need to be accurately collected and grouped carefully, in order to be able to have a broad picture of what needs to be integrated and what is sufficient for the ultimate purpose of enabling each individual man to have a sufficient basic health point. Thus, the purpose of this short narrative review is to highlight the preventive and therapeutic role of lifestyle components, particularly nutrition and physical activity, in males with osteoporosis. Finally, an evaluation of the impact of the main current diets used in recent years and the main physical activities as strategies for the safety of male bone health.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1075-1083"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830527","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}

{"title":"UBC9: a novel therapeutic target in papillary thyroid carcinoma.","authors":"Hui Zhang, Jingjing Wu, Huaiyuan Hu, Heng Tang, Kemeng Tan, Mengxue Hu, Genbao Zhu","doi":"10.1007/s40618-024-02523-y","DOIUrl":"10.1007/s40618-024-02523-y","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Despite the favorable prognosis in some patients, there remains a risk of lymph node metastasis and death in some patients. Therefore, new therapeutic strategies are required to improve PTC outcomes.</p><p><strong>Methods: </strong>In this study, we performed differential expression analysis using data from patients with PTC collected from the Cancer Genome Atlas program database, and prognostic analysis of differential genes. To understand the effects of ubiquitin-conjugating enzyme 9 (UBC9) on drug therapy, immunotherapy, immune relevance, and gene mutations in tumor cells of patients with PTC, we performed cancer drug susceptibility genomics, computed tumor immune dysfunction and exclusion, tertiary lymphoid tissues, cytolytic activity, immune infiltration, immune modulators, genomic signature differences, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Moreover, we investigated the function of UBC9 in tumor cells using a knockdown assay.</p><p><strong>Results: </strong>UBC9 expression level was significantly elevated in the tumor tissues of patients with PTC, and in vitro experiments demonstrated that UBC9 knockdown inhibited tumor proliferation and migration and promoted apoptosis. UBC9 is closely linked to immunity in PTC, and UBC9 may be a potential therapeutic target.</p><p><strong>Conclusions: </strong>Our study demonstrated that UBC9 is a novel therapeutic target for PTC and may be a potential strategy for its treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1101-1119"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537936","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}

{"title":"Long noncoding RNA FAM111A-DT promotes aggressiveness of papillary thyroid cancer via activating NF-κB signaling.","authors":"Junxin Chen, Yue Chen, Rong Huang, Pengyuan Zhang, Zijun Huo, Yanbing Li, Haipeng Xiao, Hongyu Guan, Hai Li","doi":"10.1007/s40618-025-02531-6","DOIUrl":"10.1007/s40618-025-02531-6","url":null,"abstract":"<p><strong>Purpose: </strong>Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the tumorigenesis and progression of various cancers. However, the functional roles of lncRNAs in papillary thyroid cancer (PTC) remain unclear. In this study, we investigated the functional role of the lncRNA FAM111A-DT in PTC progression and the underlying mechanisms.</p><p><strong>Methods: </strong>Different expression levels of lncRNAs in PTC were compared via analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses and qRT‒PCR were used to investigate the expression of FAM111A-DT in PTC. Cell proliferation was measured via CCK8, EdU, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. Apoptosis was detected via flow cytometry. RNA sequencing, qRT‒PCR, Western blot, immunofluorescence and dual-luciferase reporter assays were performed to assess the underlying mechanisms involved.</p><p><strong>Results: </strong>FAM111A-DT was highly expressed in PTC and associated with poor prognosis, thyroid dedifferentiation, various clinical features and the BRAF^V600E mutation in PTC patients. Overexpression of FAM111A-DT enhanced the proliferation, migration and invasion of PTC cells while reducing their degree of apoptosis. The NF-κB signaling pathway was activated in FAM111A-DT-overexpressing PTC cells. The NF-κB inhibitor PDTC attenuated the promotive effects of FAM111A-DT on aggressive phenotypes and NF-κB pathway activity in PTC cells.</p><p><strong>Conclusion: </strong>FAM111A-DT is upregulated in PTC, and its expression is associated with poor clinical outcomes. FAM111A-DT plays an oncogenic role by, at least partially, activating the NF-κB signaling pathway.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1121-1136"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957123","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}

{"title":"Evaluation of fluid status in patients with acromegaly through bioelectrical impedance vector analysis: a cross-sectional study.","authors":"Emanuele Varaldo, Nunzia Prencipe, Alessandro Maria Berton, Daniela Cuboni, Luigi Simone Aversa, Michela Sibilla, Francesca Mocellini, Fabio Bioletto, Ezio Ghigo, Valentina Gasco, Silvia Grottoli","doi":"10.1007/s40618-025-02541-4","DOIUrl":"10.1007/s40618-025-02541-4","url":null,"abstract":"<p><strong>Purpose: </strong>The acromegalic state is associated with an increase in total body water and sodium. The aim of our study was to assess the hydration status of patients with acromegaly using bioimpedance vector analysis (BIVA), differentiating patients according to their disease status (active, medically controlled or cured) and to compare the confidence and tolerance ellipses of BIVA in those patients in relation to a reference healthy population.</p><p><strong>Methods: </strong>We analyzed data from 73 consecutive patients aged 18 years or older, diagnosed with acromegaly and undergoing regular follow-up at our Division for whom a BIVA analysis was available. Patients were evaluated through BIVA and insulin-like growth factor I (IGF-I), growth hormone (GH), serum sodium and potassium, creatinine, glucose, HbA1c and plasma and urine osmolality were collected. Exclusion criteria were concurrent presence of arginine-vasopressin deficiency, dysnatremia or the presence of pathologies known to significantly alter the extracellular fluid.</p><p><strong>Results: </strong>Sixty-nine patients (M/F 34/35, age 60 ± 14 years) were enrolled in the study. As expected, patients with active disease (n = 22) presented higher IGF-I and GH levels compared to other subjects. Patients with controlled disease (n = 33) were significantly older than other individuals (p = 0.028 vs. active disease, p = 0.024 vs. cured disease). Compared to a reference healthy population, patients with either active or medically controlled disease showed significant fluid overload (p < 0.0001 for both males and females) and BIVA confidence analysis demonstrated that there were no significant differences in hydration status between the two groups (p = 0.363). On the other hand, patients with cured disease (n = 14) showed reduced hydration status compared to patients with active disease (p = 0.016), although no difference was observed compared to patients with controlled disease (p = 0.308).</p><p><strong>Conclusion: </strong>The results of our study demonstrate that patients with either active or medically controlled acromegaly present a significant overhydration compared to a healthy reference population and that alterations in body water content usually improve in individuals with cured disease.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1185-1195"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426529","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}

{"title":"The thyroid hormone activating enzyme, DIO2, is a potential pan-cancer biomarker and immunotherapy target.","authors":"A Nappi, C Miro, A G Cicatiello, S Sagliocchi, L Acampora, F Restolfer, M Dentice","doi":"10.1007/s40618-024-02526-9","DOIUrl":"10.1007/s40618-024-02526-9","url":null,"abstract":"<p><strong>Purpose: </strong>Type 2 deiodinase (D2), encoded by DIO2 gene, catalyzes the activation of the prohormone thyroxine (T4) into the bioactive hormone triiodothyronine (T3) in peripheral tissues, thereby regulating the intracellular Thyroid Hormone (TH) availability. Recently, several studies have demonstrated that a drastic increase in the peripheral activation of TH, via D2, fosters tumor progression, metastasis, and immunity.</p><p><strong>Methods: </strong>To further prove the clinical relevance of D2 in human cancer, based on public Database of The Cancer Genome Atlas (TCGA), we conducted a pan-cancer analysis of DIO2 expression in various cancer types and investigated the association of DIO2 expression with the tumor microenvironment (TME) components and immune cell infiltration, along with the DIO2 genetic alteration types.</p><p><strong>Results: </strong>Although with different expression levels between the various cancer types, the pan-cancer analysis showed that DIO2 was highly expressed in most tumors and related to the progression of some tumor types. Furthermore, DIO2 expression was also significantly correlated with TME components, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets.</p><p><strong>Conclusion: </strong>The relevance of this study is that it adds a clinical relevance to the recent demonstrations that D2 accelerates tumor invasion in animal models and poses DIO2 gene as a potential prognostic marker in various human cancers.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1149-1172"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014487","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}

{"title":"SP1 activates AKT3 to facilitate the development of diabetic nephropathy.","authors":"Shanshan Xie, Han Yang","doi":"10.1007/s40618-025-02530-7","DOIUrl":"10.1007/s40618-025-02530-7","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and has the complex pathogenesis. The previous study reported that protein kinase Bγ (AKT3) was involved in DN progression. Our aim was to explore the detailed mechanisms of AKT3 in DN development.</p><p><strong>Methods: </strong>RT-qPCR was performed to measure the levels of specificity protein 1 (SP1) and AKT3. Mesangial cells were treated with high glucose (30 mM) to form DN cell model in vitro. Western blot was conducted to detect the protein expression of AKT3, SP1, fibrosis-related proteins, and AKT/mTOR pathway-related proteins. Cell proliferation and inflammation were evaluated via MTT, EdU staining, and ELISA assays, respectively. Oxidative stress was determined via measuring ROS and MDA levels. ChIP and dual-luciferase reporter assays were carried out to verify the relationship between SP1 and AKT3. C57BL/6 mice-treated with streptozotocin for 5 days were used to establish DN mouse model in vivo, and HE and Masson staining were conducted to evaluate pathological changes of mouse kidney tissues.</p><p><strong>Results: </strong>AKT3 and SP1 were highly expressed in DN kidney tissues and HG-induced mesangial cells. AKT3 depletion could relieve HG treatment-caused cell damage of mesangial cells through repressing cell proliferation, fibrosis, inflammation and oxidative stress. SP1 can bind to the promoter of AKT3 and serve as a translation regulation factor of AKT3. SP1 overexpression worsened HG treatment-caused cell damage of mesangial cells. Moreover, AKT3 upregulation could block the suppressive effects of SP1 depletion on cell proliferation, fibrosis, inflammation and oxidative stress in HG-induced mesangial cells. SP1 depletion reduced AKT3 expression to inactivate the AKT/mTOR pathway in HG-induced mesangial cells. Besides, AKT3 knockdown inhibited the activation of the AKT/mTOR pathway to hamper the development of DN in mice through alleviating fibrosis and inflammation in vivo.</p><p><strong>Conclusion: </strong>Our results indicated that SP1 activated AKT3 and AKT/mTOR pathway to promote mesangial cell proliferation, fibrosis, inflammation and oxidative stress, thereby facilitating DN development.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1269-1281"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957161","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}

{"title":"Thyroxine overuse and clinical indices guiding successful treatment withdrawal.","authors":"Sarantis Livadas, Nicholas Angelopoulos, Anastasios Kollias, Rodis D Paparodis, Ioannis Androulakis, Panagiotis Anagnostis, Anastasios Boniakos, Dimitrios Askitis, Djuro Macut, Juan C Jaume, Leonidas Duntas","doi":"10.1007/s40618-025-02543-2","DOIUrl":"10.1007/s40618-025-02543-2","url":null,"abstract":"<p><strong>Purpose: </strong>Levothyroxine (LT4) is commonly prescribed, but there is evidence strongly suggesting that a significant proportion of these patients are on treatment without solid evidence of hypothyroidism. Small trials on treatment discontinuation, did not detect any predictors of success. Therefore, we conducted this study in an attempt to identify predicting factors for successful LT4 withdrawal.</p><p><strong>Methods: </strong>In 802 consecutive patients (83% females, mean age 48 ± 16 years) on LT4 treatment for 8.8 ± 7.3 years without a solid diagnosis of hypothyroidism, therapy was abruptly discontinued. A total of 387 persons were followed up for up to 4 months (group A) and 415 individuals who were euthyroid at 4 months post LT4 discontinuation, were followed up for up to 60 months (group B). Recurrent hypothyroidism was defined if thyrotropin (TSH) level exceeded 4.5mIU/L.</p><p><strong>Results: </strong>Among the entire cohort, 182 patients (23%) became hypothyroid, 40% of group A and 7% of group B (p < 0.001). The Τhyroid treatment Discrimination Index (T4RxDI), the product of TSH levels multiplied by the daily LT4 dose divided by BMI, was calculated. In group A, successful LT4 withdrawal was strongly indicated by a T4RxDI value < 2.78 (72% sensitivity, 66% specificity), while in group B, the corresponding value was 3.75 (100% sensitivity, 48% specificity).</p><p><strong>Conclusions: </strong>Our findings reveal considerable overuse of LT4 and propose a T4RxDI product of < 3 as a valuable predictive factor of recurrent hypothyroidism, justifying a treatment discontinuation trial. If hypothyroidism does not resume within 4 months, the risk of developing long-term hypothyroidism is likely to be minimal.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1139-1147"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081527","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}

{"title":"An integrated view of the pathophysiological crosstalk between adipose tissue, bone and cardiovascular system in men and women.","authors":"Fationa Tolaj Klinaku, Laura Comi, Claudia Giglione, Paolo Magni","doi":"10.1007/s40618-024-02516-x","DOIUrl":"10.1007/s40618-024-02516-x","url":null,"abstract":"<p><strong>Background: </strong>Obesity, bone-related and cardiovascular diseases (CVD) are among the leading global health concerns. Growing evidence suggests that these conditions share common pathophysiological pathways and disease outcomes. PATHOGENETIC INTERACTIONS OF OBESITY, CVD AND BONE-RELATED DISEASES: Obesity is a well-established risk factor for atherosclerotic CVD (ASCVD), as dysfunctional ectopic adipose tissue may produce endocrine/paracrine hormones modulating metabolic processes and inflammation, predisposing to ASCVD. Although obesityhas been considered a protective factor for bone loss, it may lead to osteoporosis development and increased fracture risk at specific sites. Biological and epidemiological evidence has demonstrated the existence of a dynamic relationship between ASCVD and osteoporosis, since atherosclerotic calcification and bone mineralization share common pathophysiological mechanisms. Therefore, addressing ASCVD, obesity, and bone-related diseases requires multiple-level approach, which involve accurate screening, lifestyle modifications and pharmacological interventions.The current evidence about the pathophysiological relationships between obesity, bone-related diseases and ASCVD is discussed herein, highlighting common risk factors, proposed biomolecular mechanisms, clinical outcomes, lifestyle changes and pharmacological treatments.</p><p><strong>Conclusions: </strong>As populations become increasingly older and obese, understanding the correlation within this triad highlights an unmet clinical need. Applying this knowledge would help to reduce both societal and individual costs, while supporting the development of novel preventive, diagnostic and therapeutic strategies to reduce morbidity and disability associated with cardio-metabolic and bone-related diseases.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1061-1074"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848182","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}

{"title":"Fasting plasma methylglyoxal concentrations are associated with higher numbers of circulating intermediate and non-classical monocytes but with lower activation of intermediate monocytes: the Maastricht Study.","authors":"Xiaodi Zhang, Marleen M J van Greevenbroek, Jean L J M Scheijen, Simone J P M Eussen, Jaycey Kelly, Coen D A Stehouwer, Casper G Schalkwijk, Kristiaan Wouters","doi":"10.1007/s40618-025-02536-1","DOIUrl":"10.1007/s40618-025-02536-1","url":null,"abstract":"<p><strong>Purpose: </strong>Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study.</p><p><strong>Methods: </strong>696 participants of The Maastricht Study (age 60.3 ± 8.4 years, 51.9% women) underwent an oral glucose tolerance test (OGTT). Fasting and post-OGTT plasma MGO concentrations were measured using mass spectrometry. Numbers and activation of circulating immune cells at fasting state were quantified using flow cytometry. Activation scores were calculated by averaging individual marker z-scores for neutrophils (CD11b, CD11c, CD16) and classical, intermediate, and non-classical monocytes (CD11b, CD11c, CX3XR1, HLA-DR). Associations were analysed using multiple linear regression adjusted for potential confounders. Stratified analyses were performed for glucose metabolism status for associations between plasma MGO levels and immune cell counts.</p><p><strong>Results: </strong>Higher fasting plasma MGO concentrations were significantly associated with higher numbers of intermediate (β = 0.09 [95%CI 0.02; 0.17]) and non-classical monocytes (0.08 [0.002; 0.15]), but with lower activation scores for the intermediate monocytes (-0.14 [-0.22; -0.06]). Stratified analyses showed that positive associations between fasting plasma MGO levels and numbers of intermediate and non-classical monocytes appear only in participants with type 2 diabetes. Post-OGTT plasma MGO concentrations were not consistently associated with immune cells counts or activation.</p><p><strong>Conclusion: </strong>Higher fasting plasma MGO concentrations are associated with higher intermediate and non-classical monocyte counts but with lower activation of intermediate monocytes.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1257-1268"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025195","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}