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The objective of this study is to investigate the relationship between altered plasma trace elements, particularly selenium (Se), with Hyper-homocysteinemia (HhCys) as a predictive factor of insulin secretion dysfunction. The study is carried out on adult Psammomys obesus, divided in 4 experimental groups: (I) Normoglycemic/Normoinsulinemic; (II) Normoglycemic/Hyperinsulinemic; (III) Hyperglycaemic/Hyperinsulinemic and (IV) Hyperglycaemic/Insulin deficiency with ketoacidosis. The data showed that a drastic depletion of Se plasma levels is positively correlated with HhCys (>15 µmol/L; p <.001), concomitantly with decreased GPx activity, GSH levels, and GSH/GSSG ratio in group IV both in plasma and liver. In contrast, SOD activity is increased (p ≤.001) in group IV both in plasma and liver. However, plasma Cu and Mn levels increased, while plasma Zn levels decreased in group IV (p <.001). Our study confirms the increase of plasma hCys levels seemed to be a major contributing factor to antioxidant capacities and alters the availability of selenium metabolism by interference with homocysteine synthesis in the insulin secretion deficiency stage. [ABSTRACT FROM AUTHOR]

Hyperhomocysteine (HHcy) is known as a risk factor for coronary artery disease (CAD). Despite the knowledge that gut microbiota related metabolism pathway shares metabolites with that of Hcy, little has been shown concerning the association between HHcy and gut microbiota. To explore their relationship in the context of CAD, 105 patients and 14 healthy controls were recruited from one single medical center located in Beijing, China. Their serum and fecal samples were collected, with multi-omics analyses performed via LC/MS/MS and 16S rRNA gene V3-V4 region sequencing, respectively. Participants from the prospective cohort were divided into CAD, CAD & HHcy and healthy controls (HC) groups based on the diagnosis and serum Hcy concentration. The results revealed significant different metabolic signatures between CAD and CAD & HHcy groups. CAD patients with HHcy suffered a heavier atherosclerotic burden compared to CAD patients, and the difference was closely associated to betaine-homocysteine S-methyltransferase (BHMT)-related metabolites and trimethylamine N-oxide (TMAO)-related metabolites. Dimethylglycine (DMG) exhibited a strong positive correlation with serum total Hcy (tHcy), and TMAO and trimethylysine (TML) were associated with heavier atherosclerotic burden. Multiple other metabolites were also identified to be related to distinct cardiovascular risk factors. Additionally, Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy. Our study suggested that CAD patients with elevated tHcy were correlated with higher atherosclerotic burden, and the impaired Hcy metabolism and cardiovascular risk were closely associated with BHMT-related metabolites, TMAO-related metabolites and impaired gut microbiota homeostasis. [ABSTRACT FROM AUTHOR]

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]

BACKGROUND There is no consistent evidence for the relationship between tea-drinking and hyperhomocysteine (hHcy). Because tea-drinking habit and hHcy have prevailed in Chinese hypertensive patients, this study aimed to investigate the association between hHcy and tea consumption in patients with hypertension. METHODS A total of 335 hypertensive participants were recruited from 7 communities. Demographic characteristics of participants were collected through face-to-face interviews using a standard questionnaire, whereas laboratory data were obtained within 1 week after patient recruitment. Multiple logistic regression analysis was performed to examine the association between tea consumption and hHcy in hypertensive patients. RESULTS Of the 335 patients, 245 had a tea-drinking habit, and 252 of them were detected with hHcy. A significant association was found between tea consumption and hHcy in hypertensive patients (adjusted odds ratio [OR] = 1.84, 95% confidence interval [CI] = 1.01–3.36, P = 0.048). Subgroup analyses showed that black tea drinking group (adjusted OR = 8.81, 95% CI = 2.74–28.33, P < 0.001) was significantly associated with the risk of hHcy, but not oolong and green tea drinking groups (P > 0.05). Furthermore, consuming a small amount (≤1 cup per day) of green tea was negatively associated with hHcy (adjusted OR = 0.19, 95% CI = 0.07–0.51, P = 0.001), whereas a large intake (>3 cups per day) of green tea was associated with high odds of hHcy (adjusted OR = 5.00, 95% CI = 1.33–18.79, P = 0.02). CONCLUSIONS These data suggest a hypothesis that selecting green tea or limiting tea consumption might reduce risk of hHcy in hypertensive patients and that warrants further study. [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]

Objective: To explore the predictive value of serum hyperhomocysteine(Hcy), uric acid(UA) and cystatin C(Cyst-C)levels in the occurrence of carotid atherosclerosis in patients with H type hypertension. Methods: A total of 163 patients with H type hypertension, who were admitted to Chongqing Zhongshan Hospital from May 2014 to May 2015, were chosen as research subjects and divided into normal carotid intima-media thickness(c IMT) group(n=51), thickened c IMT group(n=54) and carotid artery plaque group(n=58) according to the difference of c IMT. The gender, age, serum Hcy, Cyst-C, UA, blood glucose(GLU), blood lipid, blood urea nitrogen(Bun) and serum creatinine(Scr) levels among the three groups are detected and compared, and their correlation with c IMT was analyzed. The influencing factors of carotid atherosclerosis were analyzed by logistic regression analysis. Results: There were significant differences in the HDL-C, Hcy, Cyst-C and UA levels among the three groups(P<0.05). c IMT was positively correlated with the serum Hcy, Cyst-C and UA(r=0.23, 0.32, 0.30; P<0.05), negatively correlated with HDL-C(r=-0.410, P<0.05). Logistic regression analysis showed that the levels of Hcy, Cyst-C and UA were the risk factors of carotid atherosclerosis(OR=1.203, 6.395, 1.023; P<0.05).Conclusion: Serum Hcy, Cyst-C and UA levels are positively correlated with c IMT in the patients with H type hypertension. They are the independent risk factors leading to carotid atherosclerosis,which can be used to predict the occurrence and development of atherosclerosis in the early stage in clinic. [ABSTRACT FROM AUTHOR]

Homocysteine, a sulfur-containing amino acid derived from the methionine metabolism, is located at the branch point of two pathways of the methionine cycle, i.e. remethylation and transsulfuration. Gene abnormalities in the enzymes catalyzing reactions in both pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is associated with increased risk for congenital disorders, including neural tube closure defects, heart defects, cleft lip/palate, Down syndrome, and multi-system abnormalities in adults. Since hyperhomocysteinemia is known to affect the extent of DNA methylation, it is likely that abnormal DNA methylation during embryogenesis, may be a pathogenic factor for these congenital disorders. In this review we highlight the importance of homocysteinemia by describing the genes encoding for enzymes of homocysteine metabolism relevant to the clinical practice, especially cystathionine-β-synthase and methylenetetrahydrofolate reductase mutations , and the impairment of related metabolites levels. Moreover, a possible correlation between hyperhomocysteine and congenital disorders through the involvement of abnormal DNA methylation during embryogenesis is discussed. Finally, the relevance of present and future diagnostic tools such as tandem mass spectrometry and next generation sequencing in newborn screening is highlighted. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8–12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness. [Copyright &y& Elsevier]

Hyperhomocysteinemia represents elevated homocysteine (Hcys) concentrations in blood above the normal range. In humans, the normal range of homocysteine is 5.0–15.9 mM/ml. High levels of homocysteine disturb the normal epithelial functions and correlate with cardiovascular diseases even at slightly increased concentrations. In homocysteine metabolism, vitamins play an important role. The mechanism through which homocysteine triggers these effects is not yet elucidated, but the involvement of reactive species may be the answer. It is not known whether the intra- or extracellular antioxidant system is more affected by elevated homocysteine levels. We studied the effects of hyperhomocysteinemia on the intra- and extracellular antioxidant defense systems in two different types of diet in rats. Type I was food with low folic acid and vitamin B12 content and type II was food with normal amounts of these two vitamins. Hyperhomocysteinemia was experimentally induced by oral administration of methionine 2 mg/kg body weight, single daily dose, for a 15-day period. Plasma concentrations of homocysteine were measured using an HPLC method. In the response of the intracellular antioxidant defense system against hyperhomocysteinemia, we determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells, using RANDOX kits for manual use. For the extracellular response we determined the plasma total antioxidant status (TAS) also using a RANDOX kit for manual use. Our data show that methionine load induces hyperhomocysteinemia despite normal vitamin supply in rats. SOD activity rose with simultaneous decrease in GPx activity independently of diet; this might suggest that the intracellular defense system was disturbed by the rise in homocysteine level. TAS decrease suggests that the extracellular antioxidant defense was also affected. We assume that hyperhomocysteinemia is directly linked to reactive species generation and the intracellular space seems to be more affected than the extracellular one. [ABSTRACT FROM AUTHOR]