Endothelial progenitor cells (EPCs) are an independent factor predicting cardiovascular events. Visfatin plays an important role in the pathogenesis of various metabolic disorders. In this study, we examined the effects of visfatin on the apoptosis of EPCs and the mechanisms underlying these effects. Cultured EPCs pre-treated with various concentrations of visfatin, FK866 (visfatin inhibitor) and BAY11-7085 [referred to as BAY11; nuclear factor-κB (NF-κB) inhibitor] were used to investigate the association between visfatin and EPC apoptosis. Following treatment with visfatin for 48 h, the EPCs exhibited a dose-dependent increase in apoptosis and an upregulated expression of Bax, caspase-3 and NF-κB at both the mRNA and protein level, and a decreased protein expression of Bcl-2. Compared with the untreated control group, the increase in EPC apoptosis, as well as in Bax and caspase-3 expression was significant following treatment with 150 ng/ml visfatin, which also induced a dose-dependent and significant increase in the protein expression of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). All the visfatin-induced effects were suppressed by pre-treatment with FK866. Pre-incubation of the EPCs with BAY11 for 1 h followed by treatment with visfatin (150 ng/ml) for 48 h also abolished visfatin-induced apoptosis; it also abolished the promoting effects of visfatin on the expression of caspase-3, Bax, ICAM-1 and IL-6, and its suppressive effects on the protein expression of Bcl-2. On the whole, our data indicate that visfatin induces EPC apoptosis by increasing the expression of pro-inflammatory mediators partly through the regulation of NF-κB.

Diabetes mellitus (DM) is an important risk factor for cardiovascular disease. Aerobic interval training (AIT) has been recommended to patients as a non-pharmacological strategy to manage DM. However, little is known about whether AIT intervention at the onset of DM will reverse the process of diabetic cardiomyopathy (DCM). In this study, we sought to evaluate whether AIT can reverse the process of DCM and explore the underlying mechanisms. Fifty Wistar rats were randomly divided into a control group (CON), DCM group (DCM) and AIT intervention group (AIT). A high-fat diet and streptozotocin (STZ) were used to induce diabetes in rats in the DCM group and AIT group. Rats in the AIT group were subjected to an 8-week AIT intervention. Fasting blood glucose (FBG), lipid profiles and insulin levels were measured. Haematoxylin and eosin (HE) staining and oil red O staining were used to identify cardiac morphology and lipid accumulation, respectively. Serum BNP levels and cardiac BNP mRNA expression were measured to ensure the safety of the AIT intervention. Free fatty acid (FFA) and diacylglycerol (DAG) concentrations were analysed by enzymatic methods. AMPK, p-AMPK, FOXO1, CD36 and PPARα gene and protein expression were detected by RT-PCR and Western blotting. AIT intervention significantly reduced rat serum cardiovascular disease risk factors in DCM rats (P < 0.05). The safety of AIT intervention was illustrated by reduced serum BNP levels and cardiac BNP mRNA expression (P < 0.05) after AIT intervention in DCM rats histological analysis and FFA and DAG concentrations revealed that AIT intervention reduced the accumulation of lipid droplets within cardiomyocytes and alleviated cardiac lipotoxicity (P < 0.05). CD36 and PPARα gene and protein expression were elevated in the DCM group, and these increases were reduced by AIT intervention (P < 0.01). The normalized myocardial lipotoxicity was due to increased expression of phosphorylated AMPK and reduced FOXO1 expression after AIT intervention. AIT intervention may alleviate cardiac lipotoxicity and reverse the process of DCM through activation of the AMPK–FOXO1 pathway.

Purpose: The aims of this study were to determine the relationship between 25-hydroxyvitamin D [25(OH) D] and glycated hemoglobin (HbA1c) levels in male and female patients with type 2 diabetes mellitus (T2DM). Patients and Methods: The participants were adults diagnosed with T2DM recruited from Hebei General Hospital. Patient information and information regarding blood indicators were collected. The subjects were divided into no vitamin D deficiency group [25(OH) D > 20 ng/mL] and vitamin D deficiency group [25(OH) D < 20 ng/mL], and these groups were then further subdivided into male-only or female-only subgroups. And then, the subjects were divided into male group and female group in different 25(OH) D levels. Results: HbA1c levels in the vitamin D deficiency group were significantly higher than those in the no vitamin D deficiency group for all subjects. The same was true for female patients but not for male patients. There was no difference in HbA1c levels between male and female patients with T2DM, regardless of 25(OH) D deficiency. A negative correlation existed between 25(OH) D and HbA1c in all subjects, as well as in the male-only and female-only subgroups. Vitamin D deficiency was associated with high HbA1c levels before and after adjusting for confounding factors in all participants and in the female-only subgroup, but not in the male-only subgroup. Conclusion: This study confirmed that vitamin D deficiency was related with high HbA1c levels in patients with T2DM, and this relationship differs between female and male patients.

Purpose/Aims of the study: This study sought to study the levels of circulating endothelial progenitor cells (EPCs), serum visfatin, and oxidative stress in obese individuals, and their respective correlations. Materials and methods: The circulating levels of EPCs were measured through detecting CD309 and CD34 by flow cytometry. Serum visfatin concentration was measured by enzyme-linked immunosorbent assay in 31 obese men [obese group: BMI 28.9 ± 0.86 kg/m²; age 44.93 ± 1.78 years (range 40 to 47)] and 30 normal-weight men [control group: BMI 22.7 ± 1.22 kg/m²; age 44.03 ± 1.87 years (range 41 to 47)]. Indexes of oxidative stress were assayed by a colorimetric method. The relationships between circulating EPCs, serum visfatin, and oxidative stress markers were further analyzed by multiple linear regression analysis. Statistical significance was set at p < 0.05. Results: The obese group showed higher levels of serum visfatin and a lower level of circulating EPCs compared with controls. Serum superoxide dismutase (SOD) activity, total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-px) activity were significantly lower in obese subjects than in controls, while levels of serum malondialdehyde (MDA) were significantly higher. Circulating EPCs were positively associated with SOD (β = 0.306) and LnHOMA-IR (β = 0.223) and negatively associated with BMI (β = −0.321), serum visfatin (β = −0.236), and MDA (β = −0.293). Conclusions: The quantity of circulating EPCs decreases in obese individuals, along with increased serum visfatin and oxidative stress product. Visfatin and oxidative stress might therefore impact on the circulating EPCs in obese populations.

Purpose: This study aimed to investigate whether low albumin levels are a risk factor for osteoporosis (OP) in patients with type 2 diabetes mellitus (T2DM).Patients and methods: This study included adult patients with T2DM hospitalized at the Hebei General Hospital in China between 2019 and 2020. Patients were divided into groups based on OP to explore the differences between the two groups and stratified by sex. Confounding factors were screened based on the statistical results and clinical practice, and regression analysis was used to explore the relationship between albumin levels and OP.Results: In total, 125 patients (68 men and 57 women) with T2DM were included in this study. Triglyceride and high-density lipoprotein cholesterol levels significantly differed between groups. In the low-albumin group, after adjusting for all confounding factors, the P value was 0.041 and the odds ratio (OR) was 4.608 [95% confidence interval (CI): 1.063, 19.063] compared with that in the normal-albumin group. Among male patients, considering all confounding factors, the OR was 12.936 (95% CI: 1.130, 148.125) and P = 0.040 in the low-albumin group compared with that for the normal-albumin group. No such relationship was found in female patients.Conclusion: A low albumin level is a risk factor for OP in the total population and in male patients but not in female patients. Therefore, albumin levels should be considered when controlling glucose levels in patients with T2DM.

In recent years, the beneficial effects of silibinin (SIL) on nonalcoholic fatty liver disease (NAFLD) have attracted widespread attention. We tried to study the intervention effect of SIL on NAFLD, and explore the potential mechanisms and targets of SIL on NAFLD improvement. Thirty-three male C57BL6/J mice were divided into three groups, and, respectively, fed a normal diet (ND), a high-fat diet (HFD) or a HFD given SIL treatment (HFD+SIL). Biochemical indexes and histopathological changes of mice in each group were detected. In addition, quantitative proteomics analysis based on tandem mass tag (TMT) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis was performed on protein changes in the livers. SIL could reduce the weight of mice, reduce liver lipid deposition, and improve glucose metabolism. Through comparison among the three experimental groups, a total of 30 overlapping proteins were found. These identified proteins were closely linked to liver lipid metabolism and energy homeostasis. Moreover, some drug targets were found, namely perilipin-2, phosphatidate phosphatase LPIN1, farnesyl pyrophosphate synthase, and glutathione S-transferase A1. In conclusions, high-fat diet increases the expressions of proteins implicated in lipid synthesis and transport in the liver, which can result in disorders of liver lipid metabolism. SIL can decrease liver lipid deposition and increase insulin sensitivity by regulating the expressions of these proteins. It not only improves the disorder of lipid metabolism in vivo, but also improves the disorder of glucose metabolism. Graphical Abstract