High-density lipoprotein (HDL) modulates low-density lipoprotein and cell membrane oxidation through the action of paraoxonase-1 (PON1). Endoplasmic reticulum (ER) stress has been linked to a wide range of human pathologies including diabetes, obesity, and atherosclerosis. Previous studies have reported that PON1 is glycated in diabetes. The aim of this study is to investigate whether and how PON1 glycation contributes to endothelial dysfunction in diabetes. ER stress markers were monitored by western blot. Endothelial function was determined by organ bath. Incubation of recombinant PON1 proteins with high glucose increased PON1 glycation and reduced PON1 activity. Exposure of HUVECs to glycated PON1 induced prolonged ER stress and reduced SERCA activity, which were abolished by tempol, apocynin, BAPTA, and p67 and p22 siRNAs. Chronic administration of amino guanidine or 4-PBA prevented endothelial dysfunction in STZ-injected rats. Importantly, injection of glycated PON1 but not native PON1 induced aberrant ER stress and endothelial dysfunction in rats, which were attenuated by tempol, BAPTA, and 4-PBA. In conclusion, glycation of PON1 by hyperglycemia induces endothelial dysfunction through ER stress. In perspectives, PON1 glycation is a novel risk factor of hyperglycemia-induced endothelial dysfunction. Therefore, inhibition of oxidative stress, chelating intracellular Ca²⁺, and ER chaperone would be considered to reduce vascular complications in diabetes.

Background: The aim of this study was to assess the relationship between serum 25-hydroxyvitamin D [25(OH)D] and serum intact parathyroid hormone (PTH) in Chinese childbearing women, and to estimate the optimum threshold of 25(OH)D that maximally inhibits the PTH, which is considered to be the optimal status for vitamin D sufficiency. Methods: Serum samples were selected from the biological samples’ bank of the Chinese Chronic Diseases and Nutrition Survey (CCDNS) 2015. The serum 25(OH)D concentration was determined by liquid chromatography tandem mass spectrometry and the serum PTH was determined by electronic chemiluminescence. Simple linear and partial correlation analysis, locally weighted regression smooth scatterplot (LOESS), nonlinear least squares estimation (NLS), and segmented regression (SR) were utilized to estimate the relationship of 25(OH)D and PTH, and to determine the threshold of 25(OH)D. Results: A total of 1568 serum samples of 25(OH)D concentration and PTH concentration were analyzed. A significant inverse relationship between 25(OH)D and PTH concentration was observed below 15.25 (14.22–16.28) ng/mL, and PTH decreased slowly with the increase of 25(OH)D above 16.75 (15.43–18.06) ng/mL after adjusting by age, latitude, city type, season, corrected calcium, and phosphorus. A very short plateau of PTH was found at 15.25 ng/mL and 16.75 ng/mL in terms of 25(OH)D according to LOESS, NLS, and SR. Conclusions: The serum 25(OH)D was negatively correlated with the serum PTH. The threshold of VitD sufficiency was found in the range of 14.22–18.06 ng/mL in terms of serum 25(OH)D concentration for Chinese childbearing women aged 18–44 years old.

Background: Evidence regarding serum uric acid (SUA) and sarcopenia remains insufficient and controversial. Muscle mass is a basic and objective component of sarcopenia, and relative muscle loss has been used to define sarcopenia in some studies. We sought to investigate the association of SUA levels with relative muscle loss in the National Health and Nutrition Examination Survey (NHANES) 2011–2018.Methods: Relative muscle loss was defined by the Foundation for the National Institutes of Health (FNIH) as characterized by appendicular lean mass (ALM) adjusted by BMI (ALM/BMI) < 0.512 for women and < 0.789 for men. Multivariate logistic regression models were performed, and sample weights were accounted to reflect the nationally representative estimates. Restricted cubic spline regression was performed to visualize the dose–response relationship.Results: A total of 8967 individuals (mean age 39.4 ± 0.3 years, female 50.1%) were included, with a mean SUA of 5.3 ± 0.02 mg/dL; 762 patients with relative muscle loss (weight prevalence 7.1%) were identified, and participants in the highest quintile of SUA exhibited the highest prevalence, up to 10.5%, while participants in the lowest quintile presented the lowest prevalence (5.3%). After adjusting for sociodemographic, behavioural factors, morbidities and renal function related indicators, participants in the highest quintile of SUA levels presented an elevated risk of relative muscle loss, with OR of 1.78 (95% CI: 1.24, 2.56), as compared with the lowest quintile. This association remained stable across most subgroups, and stronger associations were observed in groups with BMI < 25 kg/m² and exceeding recommended physical activity levels (p for interaction < 0.05). Notably, a nonlinear association between SUA and relative muscle loss was observed in the overall populations, whereas a linear association was observed in men, participants with BMI < 25 kg/m², and participants with exceeding recommended physical activity levels, with the risk of relative muscle loss increasing as SUA levels increased (p for overall < 0.01 and p for nonlinear > 0.05).Conclusions: In summary, this study revealed that elevated SUA levels are a potentially independent risk factor of relative muscle loss among the US adults. Clinical screening for SUA levels may contribute to early detection and prevention of muscle loss.

Background: Advanced glycation end products (AGEs), a group of food processing byproducts, have been implicated in the development of various diseases. However, the relationship between circulating AGEs and sleep disorders remains uncertain. Methods: This cross-sectional study elucidated the association of plasma AGEs with sleep disorders among 1732 Chinese adults who participated in the initial visit (2019–2020) of the Tongji–Shenzhen Cohort (TJSZC). Sleep behavior was assessed using self-reported questionnaires and precise accelerometers. Plasma levels of AGEs, including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1), were quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results: In logistic regression, per IQR increment in individual AGEs was associated with an increased odds ratio of short sleep duration (CML: 1.11 [1.00, 1.23]; CEL: 1.16, [1.04, 1.30]), poor sleep quality (CML: 1.33 [1.10, 1.60]; CEL: 1.53, [1.17, 2.00]; MG-H1: 1.61 [1.25, 2.07]), excessive daytime sleepiness (CML: 1.33 [1.11, 1.60]; MG-H1: 1.39 [1.09, 1.77]), and insomnia (CML: 1.29 [1.05, 1.59]). Furthermore, in weighted quantile sum regression and Bayesian kernel machine regression analyses, elevated overall exposure levels of plasma AGEs were associated with an increased risk of sleep disorders, including short sleep duration, poor sleep quality, excessive daytime sleepiness, and insomnia, with CML being identified as the leading contributor. Insufficient vegetable intake and higher dietary fat intake was associated with an increase in plasma CEL. Conclusions: These findings support a significant association between plasma AGEs and sleep disorders, indicating that AGEs may adversely influence sleep health and reducing the intake of AGEs may facilitate preventing and ameliorating sleep disorders.

Objectives: We aimed to explore the possible effects of Kashin–Beck disease (KBD) on the risk of sarcopenia and its possible interaction in the association between the risk of sarcopenia and element concentration. Methods: This cross-sectional study was conducted among individuals 18–75 years old in Qamdo, a KBD-endemic area. All individuals received physical and radiological examinations before recruitment. Patients with KBD were enrolled in the KBD group based on a diagnosis of national criteria WS/T 207-2010. Healthy individuals without KBD were enrolled in the non-KBD group. Participants with a history of element supplements, other severe musculoskeletal diseases, or organ dysfunctions were excluded. We adopted WOMAC scores for the assessment of musculoskeletal conditions and SARC-F scores for the risk of sarcopenia. Patients with SARC-F ≥ 4 were at risk of sarcopenia. Serum element concentrations were analyzed by inductively coupled plasma mass spectrometry. Dose–relationship effects of clinical scores and element concentrations on the risk of sarcopenia were determined in correlation analysis. Risk factors were identified using univariate and multivariate regression. Statistical analysis was conducted using R software. Results: A total of 65 patients with KBD and 38 participants without KBD were enrolled in the analysis. After propensity score matching, population characteristics were comparable in the two groups, and the incidence of SARC-F ≥ 4 was determined to be higher in the KBD group (p = 0.002). The WOMAC scores were correlated with SARC-F scores in the KBD group (p < 0.001) and non-KBD (p < 0.001) group, respectively. Further analysis proved that KBD was the independent risk factor for the risk of sarcopenia (p = 0.014). Moreover, high Selenium concentrations were associated with a low risk of sarcopenia in the non-KBD group (p = 0.047), while this association was not observed in the KBD group (p = 0.239). Conclusions: KBD as an independent risk factor increased the risk of sarcopenia for patients. Although high Se concentration was associated with a low risk of sarcopenia in participants without KBD, this association was not observed in those with KBD.