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Objective: The relationship between total plasma homocysteine (tHcy) and exercise remains controversial. This study aimed to investigate the association between regular aerobic exercise and hyperhomocysteine (hHcy) in patients with hypertension.Methods: A total of 497 hypertensive patients from 7 communities of Nanjing were enrolled in this cross-sectional study. All participants were asked to complete standard questionnaires by themselves. Physical and laboratory examination were performed within 1 week after enrollment. The association between regular aerobic exercise and hHcy in hypertensive patients was estimated by a multiple logistic regression analysis.Results: Of the 497 patients, 210 had a regular aerobic exercise habit and 274 of them were detected with hHcy. Multivariate analysis revealed that exercisers have less risk of hHcy (adjusted odds ratio [OR] 0.42, 95% confidence interval [CI] 0.26-0.66) as compared to non-exercisers controlling for the established and potential confounders. Intensity, frequency, and total energy expenditure of aerobic exercise were found to be independently associated with lower hHcy risk in hypertensive patients. Gender subgroup analyses showed that this inverse relationship between regular aerobic exercise and hHcy exists in both male and female groups (adjusted OR 0.41 95%CI 0.21-0.80, and adjusted OR 0.40 95%CI 0.20-0.80, respectively).Conclusions: Regular aerobic exercise has a negative association with hHcy in this cross-sectional study. That suggests a hypothesis that doing aerobic exercise might decrease the risk of hHcy in hypertensive patients. [ABSTRACT FROM AUTHOR]

• HHcy mice were susceptible to LPS-induced AKI. • Hcy caused tubular cell inflammation and cell death via Gpr97-TPL2 activation. • AS-Ⅳ negatively regulates Gpr97-TPL2 signaling to protect against HHcy exacerbated S-AKI. Hyperhomocysteine (HHcy) plays an important role in promoting inflammation and cell death of tubular epithelial cells. However, the role of HHcy and Astragaloside IV (AS-IV) in sepsis associated acute kidney injury (S-AKI) remain unclear. A significant aspect of this study aimed to elucidate the effect of AS-Ⅳ treatment on HHcy-exacerbated S-AKI and reveal its potential mechanism. Male C57BL/6 J mice fed with specific diet containing 2% methionine were established as in vivo models, and AS-Ⅳ was orally administrated continuously for 3 weeks, and then LPS (10 mg·kg−1 bodyweight) was given by a single intraperitoneal injection. The renal morphological changes were evaluated by HE and PAS staining. RNA-sequencing analysis was applied to select key signaling. The NRK-52E cells exposed to Hcy or combined with LPS were used as in vitro models. The mRNA and protein expression levels of Gpr97-TPL2 signaling were examined by qRT-PCR and western blotting assays. In vivo , HHcy mice developed more severe renal injury and prevalent tubular inflammation after LPS injection. In vitro , the levels of NGAL, Gpr97 and TPL2 were significantly increased in NRK-52E cells induced by Hcy (1.6 mM) or in combination with LPS. Notably, the effects of Hcy on TPL2 signaling was abolished by transfecting TPL2 siRNA or treating TPL2 inhibitor, without alterations in Gpr97. However, the enhancement of Gpr97-TPL2 signaling induced by Hcy was counteracted by Gpr97 siRNA. Subsequently, our findings demonstrated that AS-Ⅳ treatment can improve renal function in HHcy-exacerbated S-AKI mice. Mechanistically, AS-Ⅳ alleviated renal tubular damage characterized by abnormal increases in KIM-1, NGAL, TPL2, Gpr97, Sema3A and TNF-α, and decreases in survivin in vivo and in vitro mainly through suppressing the activation of Gpr97-TPL2 signaling. The present study suggested that HHcy-exacerbated S-AKI was mediated mechanically by activation of Gpr97-TPL2 signaling for the first time. Furthermore, our research also illustrated that AS-Ⅳ protected against HHcy-exacerbated S-AKI by attenuating renal tubular epithelial cells damage through negatively regulating Gpr97-TPL2 signaling, proposing a natural product treatment strategy for HHcy-exacerbated S-AKI. The Gpr97 level was significantly increased in HHcy-exacerbated S-AKI in mice and renal tubular epithelial cell, and Gpr97 could regulate TPL2 and Sema3A. AS-Ⅳ inhibited HHcy-induced activation of renal inflammation and cell death by down-regulating the Gpr97-TPL2 pathway in renal tubular epithelial cells. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aims to investigate hyperhomocysteinemia (HHcy) resulted from treatment in patients with Parkinson's disease (PD) and to evaluate the therapeutic outcome of HHcy. PATIENTS AND METHODS: Ninety-three newly diagnosed PD patients were divided into Madopar group (treated with Madopar) and non- Madopar group (not treated with Madopar). Plasma Hcy levels were measured. Five months later, 67 patients presenting with HHcy were randomly divided into treatment group (n = 34) (receiving methylcobalamin 500 μg, tid, and folic acid 50 mg, tid, orally) and control group (n = 33). Madopar dosage was maintained in both groups. MRI examination was performed to detect cerebral ischemia and patients were evaluated by Webster's rating scale. Plasma Hcy levels were measured at 3-month follow-up. Webster's scores and MRI were performed at 6-month follow-up. RESULTS: At the initial visit, Hcy levels of patients of Madopar group were significantly higher than those of non-Madopar group (18.52 ± 6.48 μmol/L) vs. (15.78 ± 3.42), p < 0.05]. At 5-month follow-up, patients of the non-Madopar group presented significantly increased Hcy levels (18.97 ± 7.42 μmol/L) compare with pre-treatment Hcy levels (p < 0.05), whereas Hcy levels were slightly increased in patients of Madopar group (20.61 ± 7.87 μmol/L, p > 0.05). In the treatment group, serum Hcy levels were significantly decreased after 3-month treatment with methylcobalamin and folic acid (p < 0.01). However, serum Hcy levels were not significantly changed in patients of the control group. In addition, in the treatment group, no patient presented ischemic stroke with clinical symptoms and four patients were confirmed with new cerebral ischemic and lacunar lesions by MRI examination. However, in the control group, two ischemic strokes with clinical symptoms and 11 new cerebral ischemic and lacunar lesions were detected. Significant differences were observed between two groups (p < 0.05). Furthermore, post-treatment modified Webster scores were significantly decreased than pre-treatment scores for both groups. However, no significant differences were found between groups (p > 0.05). CONCLUSIONS: Oral administration of Levodopa in the treatment of PD can cause HHcy, which can result in increased occurrence of ischemic stroke. Supplementation of methylcobalamin and folic acid can effectively reduce Hcy level and thereby prevent the occurrence of ischemic stroke. [ABSTRACT FROM AUTHOR]