Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Multivitamin/mineral supplementation and the risk of cardiovascular disease: a large prospective study using UK Biobank data.

PURPOSE: Despite the widespread use of multivitamin/mineral supplements, the effects of multivitamin/mineral on cardiovascular disease (CVD) remain inconclusive. We aimed to prospectively investigate how multivitamin/mineral use is associated with CVD. METHODS: This population-based cohort study included 465,278 men and women who participated in the UK Biobank and were free from CVD at baseline. Participants were enrolled between 2006 and 2010 and followed-up until the end of 2018. Data on supplement use including multivitamin/mineral were collected using self-reported questionnaires. Cox proportional hazards models were used to estimate the hazard ratios of CVD events in relation to multivitamin/mineral use. RESULTS: During the follow-up, we identified 25,772 cases of CVD events, 4754 cases of CVD mortality, 18,728 cases of coronary heart disease, 6726 cases of myocardial infarction, and 4561 cases of stroke. The multivariable-adjusted hazard ratios associated with multivitamin/mineral use were 0.96 (95% CI: 0.93, 0.99) for CVD events, 0.92 (0.86, 1.00) for CVD mortality, 0.96 (0.93, 0.99) for coronary heart disease, and 0.92 (0.86, 0.97) for myocardial infarction. Subgroup analysis suggested that multivitamin/mineral use was associated with a significantly lower risk of CVD events in participants aged < 60 years and in former and current smokers (P for interaction ≤ 0.01). Sensitivity analyses showed no substantial change in the results when we excluded participants who developed CVD events during the first 2 years of follow-up. CONCLUSION: Multivitamin/mineral supplementation was associated with very modest reductions in CVD events. Age and smoking might modify these associations.

Genetic variation of habitual coffee consumption and glycemic changes in response to weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Background: Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes.Objective: We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention.Design: A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption-associated single nucleotide polymorphisms. We used general linear models to test changes in glycemic traits in groups randomly assigned to high- and low-fat diets according to tertiles of the GRS.Results: We observed significant interactions between the GRS and low compared with high dietary fat intake on 6-mo changes in fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (P-interaction = 0.023 and 0.022, respectively), adjusting for age, sex, race, physical activity, smoking, alcohol, seasonal variation, and baseline values of the respective outcomes. Participants with a higher GRS of habitual coffee consumption showed a greater reduction in fasting insulin and a marginally greater decrease in HOMA-IR in the low-fat diet intervention group.Conclusions: Our data suggest that participants with genetically determined high coffee consumption may benefit more by eating a low-fat diet in improving fasting insulin and HOMA-IR in a short term. This trial was registered at clinicaltrials.gov as NCT00072995 and NCT03258203.

Dihydromyricetin induces mitochondria-mediated apoptosis in HepG2 cells through down-regulation of the Akt/Bad pathway.

The plant flavonol dihydromyricetin (DHM) was reported to induce apoptosis in human hepatocarcinoma HepG2 cells. This study was undertaken to elucidate the underlying molecular mechanism of action of DHM. In the study, DHM down-regulated Akt expression and its phosphorylation at Ser473, up-regulated the levels of mitochondrial proapoptotic proteins Bax and Bad, and inhibited the phosphorylation of Bad at Ser136 and Ser112. It also inhibited the expression of the antiapoptotic protein Bcl-2 and enhanced the cleavage and activation of caspase-3 as well as the degradation of its downstream target poly(ADP-ribose) polymerase. Our results for the first time suggest that DHM-induced apoptosis in HepG2 cells may come about by the inhibition of the Akt/Bad signaling pathway and stimulation of the mitochondrial apoptotic pathway. Dihydromyricetin may be a promising therapeutic medication for hepatocellular carcinoma.

Determinants of hyperhomocysteinemia in healthy and hypertensive subjects: A population-based study and systematic review.

AIMS: Hyperhomocysteinemia (HHcy) is known to increase the risk of many diseases. Factors influencing HHcy in healthy and hypertensive subjects remain under-researched. METHODS: A large population-based study was conducted in 60 communities from Shenzhen, China. Responses to standardized questions on lifestyle factors and blood samples were collected from all participants after a 12-h overnight fast. Multiple linear and multivariate logistic regressions were used to explore risk factors for HHcy. Results were then compared to those from a systematic review of English-language articles listed in Pubmed, EBSCOhost, Web of Science, Embase and Cochrane libraries that investigated HHcy risk factors in healthy and hypertensive subjects. RESULTS: A total of 1586 healthy (Male/Female = 642/944) and 5935 hypertensive subjects (Male/Female = 2928/3007) participated in our population-based study. In logistic regression analyses, age, BMI and creatinine (Cr) were risk factors, while being female, fruit intake and physical activity were protective factors for HHcy in healthy subjects. In hypertensive subjects, seven [age, smoking, salt intake, systolic blood pressure (SBP), uric acid, triglycerides (TG), and Cr] and four [female, fruit intake, total cholesterol (TC), and glucose] factors were associated with higher and lower HHcy respectively. The review of 71 studies revealed that potential risk factors for Hcy included nutritional, physiologic, lifestyle habits, ethnicity, genetics, interactions between gene-environment, gene-gene, gene-nutritional, environment-environment, nutritional-nutritional. CONCLUSION: Our study indicates the potential importance of increasing folic acid and vitamin B supplementation, daily fruit and vegetable intake, regular exercise and refraining from tobacco smoking and alcohol consumption as preventive strategies for Hcy.

Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients: A Population-Based, Prospective Cohort Study.

BACKGROUND AND PURPOSE: Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. METHODS: A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. RESULTS: After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 µmol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 µmol/L) were 4.96 (3.03-8.12), 6.11 (3.44-10.85), and 1.84 (0.52-6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 µmol/L (27.92%) in patients with essential hypertension. CONCLUSIONS: Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.