International Journal of Endocrinology最新文献

Type 2 diabetes mellitus (T2DM), a metabolic disorder, has the hallmarks of persistent hyperglycemia, insulin resistance, and dyslipidemia. Protein-tyrosine phosphatase 1B (PTP1B) was found to be overexpressed in many tissues in the case of T2DM and involved in the negative regulation of insulin signaling. So, PTP1B inhibition can act as a therapeutic target for T2DM. Numerous studies claimed the anti-inflammatory, hypoglycemic, hepatoprotective, and hypolipidemic activities of Dodonaea viscosa. Previously, we generated the high-fat diet (HFD)-low dose streptozotocin (STZ)-induced diabetic male mice model and treated it with a PTP1B inhibitor (5, 7-dihydroxy-3, 6-dimethoxy-2- (4-methoxy-3- (3-methyl-2-enyl) phenyl)-4H-chromen-4-one), isolated from Dodonaea viscosa. In the current study, we aimed to investigate the De novo lipogenesis, adipocyte differentiation, augmentation of lipoproteins clearance, fatty acid uptake, antilipolysis activity, and hepatic steatosis of PTP1B inhibition in adipose and liver tissues of the HFD-STZ-induced diabetic mice model. We found the retrieval of normal morphology of adipocytes and hepatocytes in the compound-treated group. The biochemical parameters showed the gradual reduction of LDL, VLDL, TC, and TG in the serum of the compound-treated group. To further test our hypothesis, real-time PCR was performed, and data revealed the reduction of PTP1B and other inflammatory markers in both tissues, showing enhanced expression of insulin signaling markers (INSR, IRS1, IRS2, and PI3K). Our compound upregulated the adipogenic (PPARγ), lipogenic (SREBP1c, FAS, ACC, and DGAT2), lipoprotein clearance (LPL, LDLR, and VLDLR), fatty acid uptake (CD36 and FATP1), and lipid droplet forming (FSP27 and perilipin-1) markers expressions in adipocytes and downregulated in hepatocytes. Furthermore, we found elevated cholesterol efflux (in adipose and liver) and decreased lipolysis in adipocytes and elevated in hepatocytes. Hence, we can conclude that our compound protects the adipocytes from abrupt lipolysis and stimulates adipocyte differentiation. In addition, it plays a hepatic protective role by shifting clearance and uptake of lipoproteins and fatty acids to the peripheral tissues and retrieving the fatty liver condition.

Purpose: This study aimed to verify the effect of angiotensin (1-7) on improving islet function and further explore the signaling pathway that may be involved in this improvement. It also aimed to explore the effects of angiotensin (1-7) on blood glucose levels, islet function, and morphological changes in db/db mice and its potential signal pathway. Methods: Forty-five db/db mice were divided randomly into a model control group and different doses of angiotensin (1-7) intervention groups (0, 150, 300, and 600 μg/kg/d), while seven db/m mice were assigned as the normal control group. The angiotensin (1-7) intervention groups received daily intraperitoneal administration for 8 weeks, whereas the normal control group was injected intraperitoneally with an equal volume of normal saline every day for 8 weeks. Changes in weight and food intake of mice were detected. Effect of angiotensin (1-7) on lipid metabolism, islet function, the morphology of pancreatic islets, and β-cell mass on mice were evaluated. The expression of PDX-1 and GCK in pancreatic tissue was verified. Results: The group receiving angiotensin (1-7) at a dosage of 600 μg/kg/d showed a significant decrease in body weight, triglyceride levels, and fasting blood glucose, along with an improvement in glucose tolerance. In the 300 μg/kg/d group, angiotensin (1-7) tended to increase the total volume of islets. Moreover, the intervention groups exhibited a significant increase in the ratio of β cells, small islets (30-80 μm in diameter), as well as the expression levels of PDX-1 and GCK in pancreatic tissue. Conclusion: Angiotensin (1-7) could improve glucose and lipid metabolism and islet function by promoting the expression of PDX-1 and GCK genes in the pancreas of db/db mice.

Patients with atrial fibrillation (AF) are linked to an increased risk of cognitive dysfunction, and serum uric acid levels play an important factor in cognitive dysfunction. However, the optimal serum uric acid level in patients with AF remains unclear. Therefore, we aimed to explore the relationship between serum uric acid and cognitive dysfunction. 583 patients were conducted in the Affiliated Hospital of Jining Medical University. Cognitive dysfunction was assessed by the Montreal Cognitive Assessment (MoCA). The relationship between serum uric acid levels and the risk of cognitive dysfunction in patients with AF was analyzed using the smoothing spline fitting model and threshold analysis. The average serum uric acid level was (383.26 ± 110.11) μmol/L, and the incidence of cognitive dysfunction was 79.76%. There was a non-linear relationship between serum uric acid levels and the risk of cognitive dysfunction in patients with AF, and the inflection point was 352 μmol/L. At the left of the inflection point, the relationship was significant (OR = 1.02, 95% CI = 1.00-1.04). At the right of the inflection point, there was no statistical difference (p=0.101). When serum uric acid levels are less than 352 μmol/L, the risk of cognitive dysfunction increases by 2% for each unit increase in serum uric acid levels in patients with AF. The study provides evidence for the treatment of serum uric acid levels in patients with AF.

In this study, we evaluated the effects of intrabursal administration of cabergoline and N-acetylcysteine on ovarian hyperstimulation syndrome (OHSS) in an immature rat model. The study assessed body, ovarian, and uterine weights, as well as the concentrations of vascular endothelial growth factor A (VEGF-A). Moreover, levels of MDA, 4-HDA, and nitrites were assessed in ovarian homogenates, and vascular permeability was quantified in the peritoneal cavity. Ovarian morphology was characterized using histology and hematoxylin-eosin staining, determining the count of ovarian follicles and corpus luteum. Our results demonstrated a significant increase in lipoperoxidation, nitrite levels, and VEGF-A concentrations in the OHSS group compared to the control group. These biochemical alterations corroborate the successful induction of OHSS in the experimental model. Direct injection into the ovarian bursa resulted in reduced vascular permeability and VEGF-A levels, suggesting that the effects of cabergoline are predominantly ovarian. Particularly, cabergoline did not significantly alter other parameters such as ovarian weight, lipoperoxidation, nitrite levels, or morphology. Conversely, low concentrations of N-acetylcysteine (25-50 µg/kg) significantly reduced ovarian and uterine weights, VEGF-A levels, and vascular permeability. Interestingly, this dose-response relationship was not observed at higher NAC concentrations (100-200 μg/kg), suggesting a potential threshold beyond which NAC loses efficacy in these specific parameters. Our results suggest that the localized administration of N-acetylcysteine shows promise as a therapeutic strategy for OHSS by modulating key parameters associated with the syndrome. These promising results warrant further investigation into its mechanisms and efficacy, potentially expanding therapeutic options for OHSS management.

Endocrine-disrupting chemicals (EDCs), found in various cosmetic products, interfere with the normal functioning of the endocrine system, impacting hormone regulation and posing risks to human health. Common cosmetic EDCs, such as ultraviolet (UV) filters, parabens, and triclosan, can enter the human body through different routes, including skin absorption. Their presence has been linked to adverse effects on reproduction, immune function, and development. High-throughput in vitro assays, using various human cell lines, were employed to assess the effects of common cosmetic EDCs such as ethylhexyl methoxycinnamate (EHMC), benzophenone-3 (BP-3), homosalate, and parabens. Despite ongoing regulatory efforts, gaps persist in understanding their long-term impacts, particularly when they are present as mixtures or degradation products in the environment. This study focuses on recent in vitro research to investigate the mechanisms through which cosmetic-related EDCs disrupt the endocrine system and other physiological systems. The in vitro findings highlight the broader systemic impact of these chemicals, extending beyond the endocrine system to include immune, reproductive, and cardiovascular effects. This research underscores the importance of developing safer cosmetic formulations and enhancing public health protection, emphasizing the need for stricter regulations.

Aims: To explore the distribution of site-specific volumetric bone mineral density (vBMD) and analyze the mechanism of vertebral compression fractures with type 2 diabetes mellitus (T2DM) subjects using quantitative computed tomography (QCT). Materials and Methods: 304 postmenopausal women without T2DM and 274 postmenopausal women with T2DM underwent QCT scan, and all divided into three age subgroups. L1 vertebra was segmented into nine zones based on the corresponding position to the human body. Results: Whether in the T2DM or non-T2DM of each age group, from the ventral to the dorsal side of L1 vertebra, the posterior third zones were the highest, and from the head to the foot of L1 vertebra, the middle third zones were the highest (p < 0.05). Global and most zonal vBMDs of T2DM were higher than those of non-T2DM in the age group of 50-59 years old, vBMD-mp of T2DM was higher in the age group of 60-59 years old, and vBMD-mm of T2DM was higher in the age group of 70-80 years old (p < 0.05). Zonal vBMDs in T2DM were higher than non-T2DM and the difference decreases with age especially in the upper third of L1 vertebra and the lower third of L1 vertebra. Conclusions: Vertebral compression fractures and the confusion between T2DM and vBMD may be all caused by the heterogeneous distribution of vBMDs. The higher risk of T2DM with vertebral compression fractures may be associated with the different loss rate of global and site-specific vBMD, independent of vBMD itself.

Objective: To explore the feasibility and clinical application value of differentially expressed lncRNA in human peripheral blood mononuclear cell (PBMC) as a potential biomarker for postmenopausal osteoporosis (PMOP). Methods: In this study, a case-control trial was conducted to collect a total of 10 samples of PBMC from PMOP and postmenopausal-without-osteoporosis (n-PMOP) patients. RNA sequencing was performed to profile lncRNA and mRNA expression, identifying differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) based on the criteria of fold change (FC) ≥ 2 and p value < 0.05; GO and KEGG enrichment analyses were carried out for differentially expressed genes (DEGs); 10 DElncRNAs and 20 DEmRNAs were selected for lncRNA-mRNA correlation analysis and Circos plot to screen out the lncRNAs that could be used as potential biomarkers. Then, ROC curve analysis was used to evaluate the diagnostic and therapeutic value of DElncRNAs as clinical potential diagnostic markers for PMOP. Afterward, 20 PMOP and 20 n-PMOP patients were reincluded and quantitative real-time PCR (qRT-PCR) was performed to externally validate the screening of lncRNAs. Result: (1) Compared with n-PMOP, there were 1978 DElncRNAs and 1024 DEmRNAs in PMOP patients. (2) Bioinformatics technology was used to analyze the DEGs, and the GO analysis showed that the activities of the gene products were mainly related to the protein binding, membrane, plasma membrane, and extracellular region. The results of KEGG enrichment analysis showed that it was mainly enriched in PI3K-Akt signaling pathway, metabolic pathways, and pathways in cancer and focal adhesion. (3) The correlation network and Circos plot further indicated the implication of DElncRNA expression profiles in PMOP via interactions with DEmRNAs. Among them, lncRNA RAB37, lncRNA BEGAIN, and lncRNA ZNF529 had the highest number of nodes, totaling 19, possibly potential diagnostic markers for PMOP. (4) The diagnostic efficacy of the screened lncRNAs was analyzed by ROC curve. The results showed an the area under the ROC curve (AUC) of 0.960 for lncRNA RAB37, 1.000 for lncRNA ZNF529, 1.000 for lncRNA BEGAIN. (5) The qPCR results showed that lncRNA RAB37, lncRNA ZNF529, and lncRNA BEGAIN were all significantly correlated with the occurrence of PMOP (p < 0.05). However, the significant difference of lncRNA ZNF529 was superior to that of other lncRNAs. Conclusion: The lncRNA ZNF529 is significantly overexpressed in PBMC in PMOP, and bioinformatics analysis and validation experiments indicate that it is closely associated with PMOP; thus, it is expected to be a potential diagnostic marker for PMOP.

Objective: Adult growth hormone deficiency (AGHD) is characterized by central adiposity and metabolic disorders. Asprosin, a newly discovered adipokine, plays a crucial role in connecting adipose tissue function with the development of metabolic syndrome. This study aims to evaluate the circulating levels of asprosin in AGHD patients and explore the potential correlation between asprosin levels and various metabolic parameters. Subjects and Methods: Forty male patients with AGHD (mean age: 33.5 ± 9.5 yrs and mean BMI: 25.0 ± 4.5 kg/m²) and forty age-, gender-, and BMI-matched non-AGHD controls were enrolled. Medical history, anthropometric parameters (weight, height, waist circumference), and biochemical and hormonal investigations were collected from the electronic medical record system. Fat mass, fat percentage, and fat-free mass (FFM) were evaluated by bioelectrical impedance. Serum levels of asprosin were measured by ELISA. Results: Patients with AGHD demonstrated notably increased waist-to-hip ratios, triglyceride levels, and decreased HDL-cholesterol levels compared with the control group. In additionally, AGHD patients exhibited significantly higher serum levels of asprosin compared with controls (p=0.039). A notable association was observed between serum asprosin levels and FFM, triglycerides, and HDL-cholesterol levels in the whole population. Conclusions: Our study highlights distinct metabolic alterations in AGHD patients when matched for BMI with controls and investigates variations in serum asprosin levels for the first time. These findings have significant implications for identifying potential biomarkers for metabolic syndrome risk in AGHD patients and informing future treatment approaches.

Objective: Mesenchymal stem cells (MSCs) have been highly confirmed for their critical role in the treatment of different diseases. This study focuses on the mechanism of umbilical cord-derived MSCs (UC-MSCs) in the treatment of ornidazole (ORN)-induced asthenozoospermia (AS) in rats via the AKT/mTOR pathway. Methods: An animal model of AS was established in ORN-induced rats, followed by treatment of UC-MSCs and rapamycin (autophagy activator) or MK-2206 (AKT inhibitor). The sperm motility, concentration, and viability of rats were measured by an automatic sperm analyzer. Hematoxylin and eosin (HE) staining was conducted to observe the pathological injury of testicular tissue in rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was utilized to evaluate the apoptosis rate of testicular cells. Western blot analysis was performed to determine the expression of apoptosis-related proteins, autophagy-related proteins, and AKT, p-AKT, mTOR, and p-mTOR. The rate of light chain 3 (LC3)-positive cells in testicular tissue was detected by immunohistochemistry (IHC). Results: In ORN-induced AS rats, sperm motility, concentration, and viability as well as the number of mesenchymal cells and spermatogenic cells were significantly decreased, spermatogenic tubule space, apoptosis rate, and cleaved caspase-3, LC3II/I, Beclin-1, and LC3-positive cell rates were increased, and Bcl2 was downregulated. UC-MSCs could improve sperm quality and testicular injury in AS rats by inhibiting excessive autophagy. Besides, UC-MSCs could activate the AKT/mTOR pathway. Moreover, inhibition of the AKT/mTOR pathway partially reversed the therapeutic effect of UC-MSCs on ORN-induced AS rats. Conclusion: UC-MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.

Objective: The utilization of radioactive iodine-131I (RAI) has long been established as a cost-effective and conventional treatment for managing Graves' disease (GD). However, the accurate prediction of the clinical response to RAI treatment remains difficult. The successful resolution of GD through RAI therapy is typically characterized by the induction of hypothyroidism or euthyroidism. Thus, the principal aim of this study was to identify plausible predictors of RAI efficacy in the treatment of GD. Methods: The clinical data of 613 GD patients, who underwent RAI treatment for the first time, were retrospectively analyzed, including age, gender, duration of hyperthyroidism, presence or absence of ocular signs, thyroid volume, thyroid weight, thyroid function (FT3, FT4, and TSH), radioactive iodine uptake (RAIU) at 2 h/6 h/24 h (2-h/6-h/24-h RAIU) prior to RAI treatment, the highest RAIU (RAIU_max), and administered activity of 131I and 131I activity per gram of thyroid tissue. Success of RAI treatment was defined as achieving hypothyroidism or euthyroidism for more than 1 year after the initial treatment. Univariate and multivariate logistics regression analyses were conducted to identify factors that influence the efficacy of RAI treatment for GD. And at last, based on the results of the multivariate logistic regression analysis, a nomogram model was established. Results: In this study, the success rate of RAI treatment for GD was 91.2% (559/613). Univariate analysis demonstrated that several factors, including age (p=0.005), thyroid volume (p=0.001), thyroid-stimulating hormone (TSH, p=0.042), ratio of RAIU at 6 h to 24 h (6-h/24-h RAIU, p=0.048), total 131I activity (p=0.026), and 131I activity per gram of thyroid tissue (p=0.001), were significantly associated with treatment outcome. Multivariate logistic regression analysis indicated thyroid volume and 131I activity per gram of thyroid tissue as significant independent predictors of radioactive iodine therapy (RIT) efficacy. The area under the ROC curve of the established nomogram model was 0.769 (95% confidence interval [CI]: 0.692-0.846), indicating that the model has good discriminatory ability. Conclusion: Calculated-dose RAI is effective in the treatment of GD. The smaller thyroid volume and the higher 131I activity per gram of thyroid tissue are predictors of RAI efficacy in the treatment of GD.