Advanced glycation end products (AGEs) are involved in delaying the wound healing of diabetic foot ulcers. The present study investigated the effects of heme oxygenase-1 (HO-1) on oxidative stress, inflammatory insult and biological behaviors in rat dermal fibroblasts in the presence of AGEs. Rat dermal fibroblasts were cultured in the presence of AGEs (100 µg/ml), glucose (1.0 g/l or 4.5 g/l), hemin (5 µM) and chromium mesoporphyrin (CrMP; 20 µM). A bilirubin kit, reverse transcription-quantitative PCR and western blotting were used to measure the activity and mRNA and protein levels of HO-1, respectively. ELISA kits were used to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), TNF-α, IL-6, IL-1β and the viability and collagen (hydroxyproline) secretion of fibroblasts. Cell proliferation and apoptosis were measured via flow cytometry. The scratch test was performed to evaluate cell migration. The results revealed that AGEs resulted in oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, while worsened functional disorders were caused by the combination of AGEs and high-glucose treatment. Hemin treatment induced sustained high HO-1 expression, decreased the levels of ROS, MDA, 8-OHdG, TNF-α, IL-6, IL-1β and cell apoptosis, and increased cellular collagen synthesis, viability, proliferation and migration, whereas CrMP abolished the effects of hemin. It was observed that high HO-1 expression reversed the AGE-induced oxidative stress, inflammatory response and biological behavioral disorders in fibroblasts, but fibroblast function did not return to that observed under normal glucose levels. In conclusion, it was demonstrated that hemin treatment induced high HO-1 expression. HO-1 reduced the AGE-induced functional disorders in fibroblasts and may accelerate the healing of diabetic wounds by improving fibroblast biological behaviors and reducing the oxidative stress and inflammatory response.
To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA). Methods:In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis 50% in the carotid artery were measured via ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis.Results: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm, P 0.01), so as the prevalence of increased cIMT and presence of carotid plaque (both P 0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60 0.34 mg/L, 1.80 0.41 mg/L, 1.98 0.64 mg/L, P 0.05; CysC: 0.76 0.12 mg/L, 0.88 0.17 mg/L, 0.94 0.23 mg/L, P 0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (all P 0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis 50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis 50%. Conclusion:B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA. and 17%-23% in resistant hypertension 3) . Compared with essential hypertension (EH), long-term exposure to increased aldosterone levels may lead to renal, cardiac, and vascular injury, which eventually results in the significant increase in the morbidity and mortality rates due to arteriosclerotic cardiovascular
Introduction: Dehydroepiandrosterone sulfate (DHEAS) has been reported to be associated with sexual function and general psychological health respectively, however, no one has ever examined their mutual relationships in a single study. Aim: The aim of the present study was to find out whether DHEAS, general psychological health, and erectile function were all associated with each other. Methods: A cross-sectional study was conducted on 34 patients with erectile dysfunction (ED) and 32 healthy controls (HC). The levels of serum DHEAS were assessed by chemiluminescence method. Erectile function and general psychological health were measured by International Index for Erectile Function-5 (IIEF-5) and General Health Questionnaire 20(GHQ-20) respectively. Main Outcome measure: The primary outcome measure of this study was the mutual correlations of serum DHEAS levels, general psychological health and erectile function. Results: Compared to HC, patients with ED had a significant lower serum levels of DHEAS (6.43 § 2.70 mmol/L vs 9.48 § 2.82 mmol/L, P < .001) and higher scores on GHQ-20 (35.06 § 8.56 vs 24.97 § 2.55, P < .001). Multivariate binary logistic regression showed that both serum levels of DHEAS (OR = 0.667, 95% CI = 0.512−0.869, P = .003) and psychological distress (scores of GHQ-20 > 28) (OR = 6.921, 95% CI = 1.821−26.305, P = .005) were significantly associated with ED. However, no significant association between psychological distress and serum levels of DHEAS was found (OR = 0.798, 95% CI = 0.623−1.021, P = .072) after controlling for ED. Partial correlation analysis revealed that both scores of GHQ-20 (r = À0.595, P < .001) and DHEAS (r = 0.450, P < .001) were significantly correlated with scores of IIEF-5, while no significant relationship was found between scores of GHQ-20 and DHEAS (r = 0.116, P = .363) after controlling for scores of IIEF-5 and age. Conclusion: Both serum levels of DHEAS and general psychological health are significantly associated with erectile dysfunction in sexually active adult men but the relationship between general psychological health and erectile function seems to be independent of DHEAS.
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