Folic acid supplementation is not the sole factor in determining neural tube defects: The possible role of autoantibodies

Neural tube defects (NTDs) are severe but common congenital malformations. Neonates who suffer from NTDs may experience long-term complications throughout their lives. These NTD complications which have been reduced worldwide are primarily due to environmental and genetic factors. Multicenter NTD studies conducted in Malaysia report a prevalence ranging from 0.79 to 1.29 per 1000 live births based on NTD etiologies, such as anti-epileptic drug consumption and maternal folate levels. In addition, intervention studies concluded that daily consumption of 400 μg of folic acid effectively reduced NTD risk; however, this data has not been robustly tested on the entire population due to the inefficiency of the three interrelated folate transport mechanisms and autoantibody generation. In this review, we evaluated the studies indicating that folic acid supplementation may not be the sole factor in reducing NTD incidence and that autoantibodies may have an important role in the NTD etiological pathway.Key words: Neural tube defect, folic acid, methylenetetrahydrofolate reductase (MTHFR), Malaysia, anti-epileptic, folate transport mechanisms, autoantibodie

The impact of using recycled culture medium to grow Chlorella vulgaris in a sequential flow system: Evaluation on growth, carbon removal, and biochemical compositions

Excessive of carbon dioxide (CO2) emission and water pollution have been identified as the two primary challenges to humans and environment. Hence, biological carbon sequestration by microalgae is recommended as an environmentally friendly approach to capture and convert this CO2 into value-added products. However, research related to the development of efficient system to concurrently overcome low CO2 solubility in water and reduction of water footprint in microalgae cultivation is still limited in the literature. In this study, the CO2 capture by Chlorella vulgaris in a recycled cultivation medium was exploited using a sequential flow photobioreactor system. The study revealed that nutrient replenished recycled medium did not significantly affect the growth performance and lipid content of C. vulgaris. It was also observed that the CO2 capture efficiency and protein content were gradually increased from the first (SFB-RWN1) to the third (SFB-RWN3) cycle of cultivation due to the increment of carbon and nitrogen content in the microalgae cell. Besides, the lipid profile of C. vulgaris cultivated in the recycled medium comprised of high concentration of saturated (up to 32.41%) and polyunsaturated (up to 43.21%) fatty acid methyl ester (FAME). The present study suggested that growing C. vulgaris in a recycled medium is a feasible solution to fix CO2 from the atmosphere and help to reduce water footprint in the microalgae cultivation system

Association of NOTCH3 Gene Polymorphisms with Ischemic Stroke and Its Subtypes: A Meta-Analysis

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05)

A sweet promise among Malaysians [Letter to the Editor]

The prevalence of diabetes in Malaysia has increased by\ud almost twofold indicating that for every six Malaysians\ud older than 30, one is diabetic.1 In Malaysia, diabetes is\ud reportedly most common among persons of Indian\ud descent followed by the Malays and Chinese..

The influence of OLR1 and PCSK9 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

It has been reported that both OLR1 and PCSK9 genes are related to various vascular diseases such as atherosclerosis, cardiovascular disease, peripheral artery disease and stroke, in particular ischemic stroke. The prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between OLR1 rs11053646 and PCSK9 rs505151 polymorphisms and the risk of ischemic stroke remains unclear and inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of genetic polymorphisms on ischemic stroke, by analyzing the complete coverage of all relevant studies. All eligible case-control and cohort studies that met the search term were retrieved in multiple scientific databases. Data of interest such as demographic data and genotyping methods were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. A total of seven case-control studies encompassing 1897 ischemic stroke cases and 2119 healthy controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR=1.33. 95%CI:1.11-1.58) and co-dominant models (OR=1.24, 95%CI:1.02-1.51) were significantly associated with ischemic stroke. For PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR=1.36, 95%CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G>C and PCSK9 rs505151 A>G may contribute to the susceptibility risk of ischemic stroke

Microbiome and ischemic stroke: A systematic review.

BackgroundIschemic stroke is one of the non-communicable diseases that contribute to the significant number of deaths worldwide. However, the relationship between microbiome and ischemic stroke remained unknown. Hence, the objective of this study was to perform systematic review on the relationship between human microbiome and ischemic stroke.MethodsA systematic review on ischemic stroke was carried out for all articles obtained from databases until 22nd October 2020. Main findings were extracted from all the eligible studies.ResultsEighteen eligible studies were included in the systematic review. These studies suggested that aging, inflammation, and different microbial compositions could contribute to ischemic stroke. Phyla Firmicutes and Bacteroidetes also appeared to manipulate post-stroke outcome. The important role of microbiota-derived short-chain fatty acids and trimethylamine N-oxide in ischemic stroke were also highlighted.ConclusionsThis is the first systematic review that investigates the relationship between microbiome and ischemic stroke. Aging and inflammation contribute to differential microbial compositions and predispose individuals to ischemic stroke

A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke

Background and Purpose Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles.We investigated epigenetic dysregulation for the MTHFR gene among ischaemic stroke patients. Methods Cases (n=297) and controls (n=110) were recruited after obtaining signed written informed consent, following a screening process against the inclusion/exclusion criteria. Serum vitamin metabolites (folate, vitamin B12 and homocysteine) were determined using immunoassays and methylation profiles for CpGs A and B in the MTHFR gene were determined using bisulfitepyrosequencing method. Results Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73 fold. CpGs A and B were not associated with either serum homocysteine levels or ischemic stroke severity. Conclusion CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke

Association of NOTCH3 gene polymorphisms with ischemic stroke and its subtypes: A meta-analysis

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).</p

Clinical relevance of MTHFR, eNOS, ACE, and ApoE gene polymorphisms and serum vitamin profile among Malay patients with ischemic stroke

Background The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Methods Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case–controls (n = 594); serum vitamin profiles were determined using immunoassays. Results The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS −786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. Conclusions The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels

The impact of APOA5 , APOB , APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis

<b>BACKGROUND AND AIMS</b>\ud \ud Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk.\ud \ud <b>METHODS</b>\ud \ud A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.\ud \ud <b>RESULTS</b>\ud \ud A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.\ud \ud <b>CONCLUSIONS:</b>\ud \ud The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke