Impact of nitric oxide synthase 2 gene variant on risk of anti-tuberculosis drug- induced liver injury in the Malaysian population

Liver injury is a great threat associated with anti-tuberculosis (anti-TB) medication. Genetic variations in genes encoding drug-metabolising enzymes further enhance this threat. We aimed to explore genetic contributions by evaluating the impact of single nucleotide polymorphisms (SNPs) within the anti-tuberculosis (AT) metabolism pathway genes and within their respective chromosomes on anti-tuberculosis drug- induced liver injury (AT-DILI). Patients (n= 90) were recruited and 170 SNPs were genotyped using Illumina array and validated using Sanger Sequencing. The well-studied N-acetyltransferase 2 (NAT2*6) rs1799930 and cytochrome P450 2E1 (CYP2E1) C1/C1 were not significantly associated with AT-DILI in our cohort but nitric oxide synthase (NOS2A) rs11080344-C was found to be significantly higher in the cases than the controls (OR 2.73, 95% CI 1.12-6.64, P= 0.027). Association studies on all other SNPs within the anti-tuberculosis metabolism pathway genes and within their respective chromosomes also found no significant report. Our study suggests that genetic variation in NOS2A could influence the occurrence of AT-DILI

Potential medicinal herb for cardiovascular health : a comprehensive review on Salviae miltiorrhizae

Cardiovascular disease (CVD) and its associated risk factors have been ranked the number 1 cause of mortality in noncommunicable diseases worldwide and Malaysia. The high statistic in CVD mortality indicates gaps and limitations in current treatment strategies using long-term drug prescription therapies. Hence, an immediate quest for alternative and effective treatments is needed. Medicinal herbs, which are ethnopharmacologically used to treat a wide range of conditions, have been used as an alternative or supplementary treatment for CVDs and their associated risk factors. The roots of Salviae miltiorrhizae have been traditionally used for centuries to treat various diseases including neurological disorders, cancer, and even coronary heart disease. Increasing evidence demonstrated a pharmacological basis for the action of S. miltiorrhizae and its active compounds, suggesting its potential in treating CVD. The objectives of this review were first to summarize published literature and synthesize the new body of knowledge on the use of S. miltiorrhizae as the potential medicinal herb that will positively impact the cardiovascular system, and secondly to elucidate the underlying mechanisms involved in promoting cardiovascular health. It is hoped that identification of key regulatory pathways by lipophilic and hydrophilic active compounds from S. miltiorrhizae will aid further investigation of its safety and efficacy to promote the use of evidence-based traditional medicinal herbs in alleviating symptoms and improve the prognosis of CVDs and their associated risk factors

The potential of silica from rice husk ash on removal of sulphide in wastewater

The production of propylene from propane dehydrogenation process in the petrochemical sector regularly produce high concentration of sulphur in the form of sodium sulphide (Na2S). High concentration of sulphide can lead to corrosion in sewage pipes, massive fish kill and obnoxious odors into the atmosphere. Adsorption technique using lowcost and environmentally friendly adsorbents derived from natural resources such as rice husk ash (RHA) may offer a suitable alternative for in situ removal of contaminants such as sodium sulphide in industrial wastewater. In this work, the use of silica synthesized from RHA was investigated for its potential in removing high concentration of sulphide (S2-) in the form of sodium sulphide from wastewater. Results showed that pure silica with the size around 0.9 to 2.0 μm was successfully synthesized from RHA. Significant reduction of sulphide level was observed after being treated with RHA based silica calcined with clay compared to other adsorbents such as chemically treated nanoporous zeolite and natural clay itself with more than 90 % removal after 120 minutes of treatment with the value of the pseudo-first-order rate constant, k of 0.1404, 0.14 and 0.1519 for silica compared to zeolite. This suggests that the use of silica derived from RHA has a potential to be used as sulphide remover in industrial wastewater without extensive chemical treatment to improve its removal capacity

Interspecific variation in the diet of Symphalangus syndactylus and Macaca nemestrina at Genting Highlands, Pahang, Peninsular Malaysia

Primate communities in the Genting Highlands consist of a single species of Hylobatidae and four species of Cercopithecidae, which are known to exhibit social interaction behaviour. Thus, a study on the diets of Symphalangus syndactylus (siamang; family Hylobatidae) and Macaca nemestrina (pig-tailed macaque; family Cercopithecidae) was carried out at Genting Highlands, in order to compare the dietary preferences and interspecific competition between the two primate families. A DNA metabarcoding approach was used to analyse diet intake using non-invasive samples based on the trnL region. Based on the 140 amplicon sequence variants (ASVs) generated, 26 plant orders, 46 different families, 60 genera and 49 species were identified from 23 different plant classes. Fabaceae and Moraceae were classified as the most preferred plants at the family level for S. syndactylus; meanwhile, Piperaceae and Arecaceae were classified as the most preferred for M. nemestrina. Only six out of the 60 different plant genera classified in this study, were found to be consumed by both species. Therefore, the low similarity of preferred plants in the diets between the two families suggests that there is little interspecific competition. These findings are important for future conservation management of highland primates, especially in the Genting Highlands

Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers

MicroRNAs (miRNAs) are small regulatory molecules that are involved in posttranscriptional modifications. These noncoding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potential as noninvasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease progression can induce active and selective loading of miRNAs into exosomes. In this paper, we first review the mechanisms of miRNA loading into exosomes, followed by the roles of exosomal miRNAs in the development of hypertension, and the potentials of exosomal miRNAs as biomarkers in comparison with other free circulating miRNAs. Finally, challenges and future research surrounding exosomal miRNAs will also be discussed. This review will aid in the understanding of noninvasive biomarkers for the early diagnosis of hypertension and for probing therapeutic efficacy

A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease

The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69–3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12–3.37, p = 0.018; OR 3.51, 95% CI 1.69–7.26, p = 0.001 and OR 2.05, 95% CI 1.25–3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85–3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05–3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17–3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurence of fibrosis in patients with NAFLD

The role of single nucleotide polymorphisms and copy number variations in the spectrum of non-alcoholic fatty liver disease / Shamsul bin Mohd Zain

Non-alcoholic fatty liver disease (NAFLD) has been recognised as a growing public health problem worldwide. NAFLD is a spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign condition whereas NASH can potentially progress to serious liver complications, including liver cancer. Genetic factors have been shown to play a significant role in the pathogenesis of NAFLD and may be responsible for the different phenotypes among individuals, including predisposition to severe liver disease. Genomic variability may present in various forms such as single nucleotide polymorphisms (SNPs), structural alterations (deletion, duplication and inversion), variable number of tandem repeats (VNTRs) and presence or absence of transportable element. Of all these variations, the commonest is the SNP. Copy number variation (CNV) is another type of mutation that could serve as a genetic marker for the NAFLD spectrum, and to date, there is no published report on CNV in NAFLD. This study aimed to investigate the association between SNPs of candidate genes with susceptibilty to NAFLD and the severity of the underlying liver disease. This study further identified genomic amplifications and deletions (CNVs) in the spectrum of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls without NAFLD were genotyped for polymorphisms of various candidate genes. Whole-genome array comparative genomic hybridization (aCGH) method was used to detect CNVs in a total of 40 patients with NASH and 40 age, gender, and ethnicity-matched controls. The polymorphisms of PNPLA3, LEPR¸ and GCKR render susceptibility to NAFLD (OR 2.23, 95% CI 1.60-3.11, P < 0.0001; OR 1.64, 95% CI 1.18-2.28, P = 0.003; and OR 1.49, 95% CI 1.09-2.05, P = 0.012, respectively) while SNPs of AGTR1 render protection against the condition (OR 0.40, 95% CI 0.20-0.81, P = 0.01). The G allele of both the PNPLA3 rs738409 and the AGTR1 rs3772622 were associated with increased fibrosis score (P < 0.05). For LEPR rs1137100, the G allele was associated with lower fibrosis score (P < 0.05). Analysis of gene-gene interaction revealed a strong interaction between the AGTR1, LEPR and GCKR genes with the PNPLA3 gene (empirical P = 0.007, empirical P = 0.001 and empirical P = 0.003, respectively). Genome wide profiling identified five most frequently amplified CNVs located on the chromosome 14q11.2 (62.5%), 12p13.31 (50.0%), 11p15.4 (45.0%), 5p15.33 (42.5%), and 12p13.2 (40.0%). The most frequently deleted CNVs were located on chromosome 11q11 (35.0%), 12p13.2 (32.5%), 16q12.2 (32.5%), 4q13.2 (32.5%), 1q21.3 (32.5%), and 14q24.3 (32.5%). It can be hypothesised that these CNVs may be implicated in mechanisms that lead to progression to NASH. Of particular note was a 0.02 Mb deletion on chromosome 16q12.2. This region is rich in carboxylesterase 1 gene (CES1) that is important in cholesterol transportation leading to fatty liver. Downstream studies to validate findings are being pursued. Overall, this study showed the complex nature of NAFLD involving multiple gene interactions. The copy number findings are novel and could serve as potential genetic marker for the identification of the potentially progressive form of NAFLD

A common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: A meta-analysis

Background and Aim: Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD. Methods: We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined. Results: This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14-1.36, P<0.00001). Analysis also revealed significant associations with different alternative genetic models for the inheritance: dominant, recessive, and homozygote (OR 1.40, 95%CI 1.23-1.61, P<0.00001; OR 0.79, 95% CI 0.68-0.91, P=0.001, and (OR 1.27, 95% CI 1.10-1.47, P=0.001, respectively), but not the heterozygote model. Population subgroup analysis demonstrated similar effect size in both Asians and non-Asians (OR 1.27, 95%CI 1.12-1.45, P=0.0003 and OR 1.22, 95%CI 1.10-1.37, P=0.0003, respectively). Conclusions: Our meta-analysis provides evidence of significant association between GCKR rs780094 and risk of NAFLD. Similar effect size was demonstrated in both Asian and non-Asian populations

Energy consumption model for virtual machines in cloud data centre

Cloud computing is a growing demand that allows a business to drive their goals using good Information Technology (IT). The tremendous increased in computing resources usage introduce several challenges to IT service providers. One of the key issues is the high energy consumption of the data centres. Virtualization has been used as a technique to reduce hardware footprint and thus realizing power efficiency in the data centre. However, improper placement technique has caused many virtual machines being provisioned inefficiently. Consequently, the physical servers installed as hosts are utilizing high power in data centre while the provisioned virtual machines are underutilized. This problem defeats the very reason why cloud computing was first introduced. This study focuses on identifying a relationship between virtual Central Processing Unit (CPU) of cloud servers, physical CPU, and total power consumption of its hypervisor. We developed a model to estimate power requirements for virtual machines (VM) in a cloud data centre and introduce an algorithm to place the virtual machines within the virtual data centre automatically. The model is applied to steady-state cloud data centres or in systems engineering design phase. The model can also be extended in determining a cloud server’s chargeback model based on an individual could server proportional power consumption