International Journal of Endocrinology最新文献

Background: Anaplastic thyroid carcinoma (ATC) is a rare, aggressive cancer with a poor prognosis and limited treatment options. KIF23, a key regulator of cell division, has been implicated in tumor progression, but its role in ATC remains unclear. This study investigates the effects of KIF23 on ATC cell viability, migration, invasion, and signaling pathways.

Methods: ATC cell models were generated by transfecting cells with KIF23 silencing or overexpression plasmids. KIF23 expression was measured by RT-qPCR and Western blot. Cell viability, oxidative stress, migration, and invasion were assessed using CCK-8, ELISA, scratch, and Transwell assays. Wnt/β-catenin pathway activation was analyzed by Western blot, and ferroptosis was induced by erastin.

Results: Silencing KIF23 significantly decreased cell viability, increased oxidative stress, and reduced cell migration and invasion. Overexpression of KIF23 enhanced cell viability, migration, and invasion, and these effects were partially reversed by the Wnt/β-catenin pathway inhibitor NTZ. KIF23 overexpression led to a decrease in intracellular ROS levels and reduced oxidative stress markers. Erastin treatment, in contrast, increased ROS levels, reduced cell viability, and suppressed migration and invasion. In the OE-KIF23 + erastin group, erastin partially reversed the pro-survival and pro-motility effects of KIF23 overexpression, with ROS levels and functional readouts shifting toward those of erastin-treated cells, indicating that KIF23 interacts with ferroptosis-related oxidative stress regulation in ATC cells.

Conclusion: KIF23 regulates ATC cell viability, migration, and invasion via the Wnt/β-catenin signaling pathway and ferroptosis. These findings suggest that KIF23 may be a potential therapeutic target for ATC treatment.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel composite marker that reflects systemic inflammation, nutrition, and immune status. However, its association with mortality among individuals with diabetes or prediabetes remains uncertain. This study aimed to assess the relationship between the CALLY index and both all-cause (ACM) and cardiovascular mortality (CVM) in U.S. adults with diabetes or prediabetes.

Methods: A total of 8463 adults with diabetes or prediabetes from the U.S. NHANES (2003-2010 and 2015-2018) were included in the analysis. Cox proportional hazards models were used to evaluate potential linear associations between the CALLY index and ACM and CVM. Kaplan-Meier survival curves and log-rank tests were used to compare cumulative survival across groups. Restricted cubic spline (RCS) models were applied to examine potential nonlinear associations.

Results: During an average follow-up of 7.83 years, 1391 participants died, 470 from cardiovascular causes. After adjusting for all confounders, the natural log-transformed (ln) CALLY index was inversely associated with ACM (HR = 0.83, 95% CI: 0.79-0.88) and CVM (HR = 0.82, 95% CI: 0.74-0.92). Compared to participants in the lowest quartile of the ln CALLY index, those in the highest quartile had significantly lower risks of ACM (HR = 0.67, 95% CI: 0.55-0.81) and CVM (HR = 0.66, 95% CI: 0.45-0.98). Kaplan-Meier survival analysis showed significantly higher survival probabilities among individuals in higher ln CALLY index quartiles (p < 0.001). RCS models further indicated a nonlinear relationship between the ln CALLY index and both ACM and CVM (p < 0.0001 for nonlinearity).

Conclusions: A higher CALLY index is independently associated with lower risks of ACM and CVM among individuals with diabetes or prediabetes. These findings suggest that the CALLY index may serve as a valuable marker for monitoring mortality risk in these populations.

Background: The diagnosis and management of gestational diabetes mellitus (GDM) before 24 weeks of gestation are controversial topics. While some retrospective studies have shown that early diagnosis of GDM significantly impacts pregnancy outcomes, recent randomized controlled trials have found no benefit. This disparity in findings raises essential questions about the optimal timing of GDM diagnosis and its potential impact on maternal and neonatal outcomes.

Objective: We aimed to compare pregnancy outcomes between women with GDM diagnosed early and those diagnosed during routine second-trimester screening.

Methods: This retrospective cohort study compared outcomes between women with early GDM diagnosed at < 14 weeks and those with GDM diagnosed at 24-28 weeks. Maternal and neonatal outcomes and the need for pharmacotherapy were compared using appropriate statistical tests.

Results: Of 437 women with GDM, 113 (25.9%) were diagnosed early, and 324 (74.1%) were diagnosed in the second trimester. Women diagnosed early had a higher prepregnancy BMI and gained less weight during pregnancy compared to those diagnosed later (p < 0.05). However, maternal and neonatal outcomes and the need for pharmacotherapy did not significantly differ between the groups.

Conclusion: An early diagnosis of GDM before 14 weeks, despite a higher BMI, was associated with less gestational weight gain but did not lead to significant differences in pregnancy outcomes or mode of treatment compared to later diagnosis.

Objective: This study aimed to investigate the relationship between asthma and the risk of Type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2016.

Methods: Weighted t-tests and weighted chi-square tests were used to compare the baseline characteristics between patients with T2DM and individuals without T2DM. Weighted multivariate logistic regression models were used to determine the association between asthma and the risk of T2DM. Two-sample univariate Mendelian randomization (MR) was performed to analyze asthma and the risk of T2DM.

Results: Among the 2348 participants included, the prevalence of asthma was 70.9% in T2DM patients. The results of the weighted multivariate logistic regression models revealed that asthma was significantly positively linked to T2DM risk, with odds ratios of 2.24, 2.26, and 1.92 in Models 1, 2, and 3, respectively. The fitting curve analysis demonstrated that asthma was positively correlated with the risk of T2DM. The MR results revealed a marked causal effect of asthma on T2DM, identifying asthma as a risk factor for T2DM. Sensitivity analysis confirmed the robustness of MR findings.

Conclusion: Asthma was significantly and positively associated with T2DM risk, indicating that it serves as a risk factor for the onset of this condition.

Purpose: Neural EGF-like 1 (Nell-1), originally implicated in craniosynostosis, has been identified as a key regulator in osteogenic processes. While preclinical data were encouraging, clinical studies correlating serum Nell-1 levels with osteoporosis remain scarce. This study aims to investigate the relationship between circulation Nell-1 level and bone turnover markers, bone mineral density (BMD), bone microstructure, muscle strength, fall risk, and fractures in Chinese postmenopausal women.

Methods: Serum Nell-1 levels were measured in 123 Chinese postmenopausal women. Muscle function was evaluated through grip strength tests, the Short Physical Performance Battery (SPPB), and the Timed Up and Go (TUG) test. Dual-energy X-ray absorptiometry was used to assess areal bone mineral density (aBMD), lumbar trabecular bone score (TBS), and muscle mass. High-resolution peripheral quantitative computed tomography (HR-pQCT) was applied to determine volumetric bone mineral density (vBMD), analyze bone microarchitecture, and estimate bone strength.

Result: Postmenopausal women with higher serum Nell-1 levels had higher aBMD and total volumetric bone mineral density (Tot.vBMD) at the distal tibia, larger cortical area (Ct.Ar) and thicker cortical thickness (Ct.Th) at the distal tibia, and higher bone strength. There was a significant negative association between serum Nell-1 levels and C-terminal cross-linking telopeptide of type I collagen (β-CTX), while no significant correlations were observed between serum Nell-1 levels and muscle mass or function.

Conclusion: Postmenopausal women with higher serum Nell-1 levels exhibited higher BMD and bone strength, indicating its potential as a therapeutic invention for osteoporosis.

Objective: To investigate the association between serum human epidermal growth factor receptor 2 (HER2) levels and metabolic syndrome (MS) in women and to explore the relationship between HER2 and the use of commonly prescribed metabolic medications.

Methods: A total of 532 women who visited Nanjing Drum Tower Hospital between January 2021 and January 2023 were enrolled. Participants were classified into a non-MS group (n = 278) and an MS group (n = 254) according to the diagnostic criteria of the Chinese Diabetes Society (2020 edition). General characteristics and serum HER2 levels were compared between groups. Based on serum HER2 levels, participants were further categorized into quartiles (Q1 [< 7.4 ng/mL], Q2 [7.4-8.5 ng/mL], Q3 [8.6-9.9 ng/mL], and Q4 [> 9.9 ng/mL]), and clinical parameters were compared among these groups. Spearman correlation analysis was performed to examine the relationships between HER2, MS-related indicators, and medication use. Logistic regression analysis was conducted to identify independent risk factors for MS.

Results: Serum HER2 levels were significantly higher in the MS group compared with the non-MS group (8.10 [7.10-9.10] vs. 9.25 [8.10-10.80] ng/mL, p < 0.001). The prevalence of MS increased progressively across HER2 quartiles: 31.30% (Q1), 36.43% (Q2), 50.00% (Q3), and 72.39% (Q4) (p < 0.001). Serum HER2 levels were positively correlated with body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting C-peptide (FCP), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.001) and negatively correlated with age, high-density lipoprotein cholesterol (HDL-C), and the use of renin-angiotensin system inhibitors and statins (all p < 0.001). Logistic regression analysis showed that higher HER2 levels remained a significant risk factor for MS after adjustment for confounders, and compared with Q1, the risk of MS in Q4 remained significantly higher in fully adjusted models.

Conclusion: The use of renin-angiotensin system-targeting antihypertensive agents or statins was associated with significantly reduced serum HER2 levels. Increasing serum HER2 levels correlated with a higher prevalence of MS, suggesting that elevated HER2 may serve as an independent risk factor and a potential biomarker for MS in women.

This study aimed to investigate the role of N⁶-methyladenosine (m⁶A) methylation in osteogenic differentiation during osteoporosis (OP). Serum specimens were obtained from 25 individuals diagnosed with OP and 25 age-matched healthy controls. In parallel, MC3T3-E1 preosteoblastic cells were employed for in vitro functional assays. Expression levels of m⁶A-associated genes were quantified using qPCR. Osteogenic potential was evaluated by measuring ALP activity with an ALP assay kit and by assessing matrix mineralization through Alizarin Red S staining. RIP and dual-luciferase reporter assays were performed to elucidate the molecular interactions involved. To corroborate the in vitro observations, an ovariectomized (OVX) mouse model of OP was established for in vivo validation. The results revealed a significant downregulation of AlkB Homolog 5 (ALKBH5) in both serum samples from OP patients and MC3T3-E1 cells undergoing osteogenic differentiation. Moreover, enforced expression of ALKBH5 suppressed osteogenic differentiation in these cells. Mechanistically, ELK1 was found to be a key downstream effector of ALKBH5. Additionally, YTH domain family protein 2 (YTHDF2) was demonstrated to function as the m⁶A reader that specifically recognizes the ALKBH5-mediated demethylation site on ELK1 mRNA. Rescue experiments confirmed that ELK1 overexpression or YTHDF2 knockdown promoted osteogenic differentiation, whereas these effects were abolished by ALKBH5 overexpression or ELK1 silencing. In OVX mice, ALKBH5 knockdown mitigated bone loss, improved bone strength, and restored ELK1 expression. Notably, ELK1 inhibition reversed the protective effects of YTHDF2 knockdown on bone loss and mechanical strength in OVX mice. In conclusion, ALKBH5/YTHDF2 axis might be involved in osteogenic differentiation via regulating ELK1 (a key downstream effector), which might provide a new insight for OP treatment.

Background: Obesity and abdominal obesity are major public health issues closely related to metabolic diseases. Serum α1-acid glycoprotein (SSAGP), an acute-phase reactant influenced by inflammation and metabolic status, has an unclear relationship with obesity and abdominal obesity. This study investigates this association in women.

Methods: Using cross-sectional data from NHANES (2015-2018), 2219 adult women were divided into three groups based on SSAGP levels (low, medium, and high). Multiple regression analyses assessed the relationship between SSAGP and BMI, waist circumference, obesity (BMI ≥ 30 kg/m²), and abdominal obesity (waist circumference ≥ 90 cm). Threshold and interaction analyses were also conducted.

Results: As SSAGP levels increased, BMI, waist circumference, fasting blood glucose, insulin, and hs-CRP levels rose significantly (p < 0.001), while HDL levels decreased (p < 0.001). SSAGP was positively correlated with BMI, waist circumference, obesity, and abdominal obesity (p < 0.0001). After adjusting for confounders, a one-unit increase in SSAGP was associated with a 4.42 increase in BMI (95% CI: 3.08, 5.76), a 12.18 cm increase in waist circumference (95% CI: 9.22, 15.14), a 3.63-fold increase in obesity risk (95% CI: 1.96, 6.72), and a 10.75-fold increase in abdominal obesity risk (95% CI: 4.85, 23.85). Threshold effect analysis showed an inflection point (K = 1.2), with SSAGP having a stronger promoting effect below this point and an inhibitory effect above it (p < 0.001). Educational level significantly influenced the SSAGP-obesity relationship (p = 0.0096).

Conclusion: SSAGP levels are significantly associated with obesity and abdominal obesity in women, with educational level playing a modulatory role. SSAGP may serve as a potential biomarker for obesity risk. Future studies should explore the causal relationships and underlying mechanisms.

[This corrects the article DOI: 10.1155/2013/405127.].

The increasing global prevalence of obesity, exacerbated by factors such as high-fat diets and reduced physical activity, poses a substantial risk for lifestyle-related diseases, particularly in postmenopausal women. Premenopausal women initially have a lower incidence of cardiovascular disease than men, but this risk increases after menopause, highlighting menopause as a critical risk factor. Our previous study showed that the extract of Cordyceps militaris (CM) modulates androgen metabolism partially by inhibiting the gene expression of catabolizing enzyme 5α-reductase. In this study, we investigated the effect of CM on estrogen deficiency-induced obesity in ovariectomized (OVX) mice fed a 0.1% CM diet (estimated human equivalent dose: 7.5 g/day) for 52 days. OVX mice had increased body weight, which subsequently decreased with CM, without altering daily food intake. Regarding visceral fat, CM suppressed OVX-induced adipogenic markers (Pparg, Cebpa, Cebpb, Fabp4, and Adipoq) and protein levels of C/EBPβ, PPARγ, and p-AKT. CM effectively reversed the OVX-induced reduction in the levels of adipose Cyp17a1 and Hsd17b1, key enzymes involved in steroid hormone biosynthesis, increased the cellular senescence markers p21 and p53, and decreased Lmnb1 expression. CM reduced the expression of oxidative stress markers HO-1, NRF2, and 4-HNE. Moreover, CM increased uterine weight and serum superoxide dismutase in 17β-estradiol-treated OVX rats. These findings suggested that CM, particularly its component cordycepin, holds promise as a natural agent for mitigating weight gain, particularly in the context of postmenopausal obesity.