Gonadal hormones and metabolic syndrome in middle-aged and elderly males: results from a prospective cohort study in China.

Background: Research has shown that gonadal hormones are involved in metabolic pathways relevant to metabolic syndrome (MetS). Nevertheless, no longitudinal study has been conducted on the association between SHBG and MetS in Chinese. The objective of our study was to determine whether there is any association between middle-aged and elderly males in China. Methods: A total of 531 eligible male subjects, aged above 40 years or older, without MetS at baseline, were recruited. Sex hormone binding globulin (SHBG), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. A harmonized definition and recommended thresholds for the Chinese population were used to determine metabolic syndrome. Results: During 3.2 years of follow-up, 20.7% of subjects had developed MetS. Compared with the non-MetS group, subjects in the new-onset MetS group had significantly lower SHBG (43.5 nmol/L [28.8, 74.9] vs 53.7nmol/L [33.8, 115.0], P=0.0018), TT (18.1nmol/L [13.6-21.7] vs 19.5nmol/L[15.0-23.6], P=0.0204), and LH (5.13mIU/L [3.63-7.29] vs 5.87mIU/L [4.05-8.36]) at baseline. The incidence of MetS was decreased according to elevated SHBG quartiles (Q1:26.9%, Q2:22.7%, Q3:21.1%, Q4:12.1%, P for trend =0.0035), TT (Q1: 25.2%, Q2:23.7%, Q3: 17.3%, Q4: 16.7%, P for trend=0.0425), and LH (Q1:25.0%, Q2:21.8%, Q3: 21.8%, Q4: 14.3%, P for trend=0.0411). Compared with those in quartile 4, the OR[CI] of incident MetS for participants in Quartile 1 was 2.33[1.13-4.79] after multiple adjustments. But associations between incident MetS and different quartiles of LH, TT, and FSH were not observed after multiple adjustments. In the subgroup analyses, the significant association between SHBG level and Mets was detected in subjects over 60 years or older, with normal BMI, without insulin resistance, and with eGFR ≥90 mL/min per 1.73m2. Conclusion: Compared with TT, LH, and FSH, a lower level of SHBG is significantly related to the incidence of MetS among middle-aged and elderly males in China.

Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing.

The protective effects of methylene blue on astrocytic swelling after cerebral ischemia-reperfusion injuries are mediated by Aquaporin-4 and metabotropic glutamate receptor 5 activation.

Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.

Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population-based study.

BACKGROUND: Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co-association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR. MATERIALS AND METHODS: In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model. RESULTS: In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min. CONCLUSION: High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.