Effects of palm oil derived tocotrienol rich fraction and vitamin e isomers on biomarkers of early atherogenesis in stimulated human umbilical vein endothelial cells

This study was conducted to investigate the effects of tocotrienol rich fraction (TRF), α-TOC, and pure TCT isomers (α-. γ- & δ-TCT) on inflammation, endothelial activation, nuclear factor kappa B (NFκB), endothelial nitric oxide synthase (eNOS) and monocyte binding activity (MBA) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of α-TOC, pure TCT isomers and TRF (0.3-10 μM) together with lipopolysaccharides (LPS) for 16 h. Culture medium and cells were collected and measured for the protein and gene expression of IL-6, TNF-α, NFκB, ICAM-1, VCAM-1, e-selectin, and eNOS. Monocyte binding activity (MBA) was measured by Rose Bengal staining. Area under the curve (AUC) analysis revealed that TRF and pure TCT particularly γ- and δ- isomers, showed better inhibition of inflammation and endothelial activation, MBA and greater eNOS increment than α-TOC. These suggest that TRF and pure TCT isomers have potential as preventive anti-atherogenic agents by attenuating the release of early biomarkers of atherogenesis which is better than α-TOC in LPS-stimulated human endothelial cells

In Vitro Atheroprotective Effects of Trigonella Foenum Graecum (TFG) and its Saponins in LPS-Stimulated Human Coronary Artery Endothelial Cells

There has been a shift towards utilizing natural products as an adjunct therapy to standard treatment in the prevention of coronary artery disease, and Trigonella foenum graecum (TFG) is one of the potential natural products of interest. In the present study, we attempted to determine the effects of TFG and its saponins on atherosclerosis related biomarkers in vitro. Protein expression of markers of inflammation, endothelial activation and transcription factors were measured by Procarta™ and ELISA assays. Gene expression of the same markers were determined by qPCR and the interaction between monocytes and HCAECs were evaluated through monocyte binding assay following 16 h of treatment with TFG and saponins. Both TFG and its saponins exhibited reducing effects on atherosclerosis-related markers. Based on the area under the curve (AUC) analysis, TFG reduced protein and gene expressions of ICAM-1 and VCAM-1 better than the saponins, while saponins reduced E-selectin expression better than TFG. Saponins showed a reduction of gene and protein expressions of IL-6, IL-8, NF-κB p50 and p65 better than TFG. TFG is more effective in reducing binding of monocytes to endothelial cells than saponins. TFG better reduced endothelial activation but exerted weaker anti-inflammatory effects than saponins, suggesting the possible synergism with other compounds in the crude extract which enhances attenuation of endothelial activation while inhibiting anti-inflammatory properties of saponins in the crude extract

Effects of palm oil derived tocotrienol rich fraction and vitamin e isomers on biomarkers of early atherogenesis in stimulated human umbilical vein endothelial cells

This study was conducted to investigate the effects of tocotrienol rich fraction (TRF), α-TOC, and pure TCT isomers (α-. γ- & δ-TCT) on inflammation, endothelial activation, nuclear factor kappa B (NFκB), endothelial nitric oxide synthase (eNOS) and monocyte binding activity (MBA) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of α-TOC, pure TCT isomers and TRF (0.3-10 μM) together with lipopolysaccharides (LPS) for 16 h. Culture medium and cells were collected and measured for the protein and gene expression of IL-6, TNF-α, NFκB, ICAM-1, VCAM-1, e-selectin, and eNOS. Monocyte binding activity (MBA) was measured by Rose Bengal staining. Area under the curve (AUC) analysis revealed that TRF and pure TCT particularly γ- and δ- isomers, showed better inhibition of inflammation and endothelial activation, MBA and greater eNOS increment than α-TOC. These suggest that TRF and pure TCT isomers have potential as preventive anti-atherogenic agents by attenuating the release of early biomarkers of atherogenesis which is better than α-TOC in LPS-stimulated human endothelial cells

Analysis of five deep-sequenced trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo populations

BackgroundRecent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated.ResultsWe analyzed the whole-genome deep sequencing data (30x) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81x10(-8) - 1.33x10(-8), 1.0x10(-9) - 2.9x10(-9), and 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples.ConclusionOur study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia

Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension

Abstract Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common – affecting at least one third of the world’s adult population – but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment – an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN

Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis

Background: Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined. Aim: To determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits. Methods: Thirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed 1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each group was subdivided into three intervention arms: 1) T3–4 mg/kg, 2) T3–15 mg/kg and 3) vehicle without T3 (T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability. Results: In B1, atherosclerotic lesion in T3–4 mg/kg group was significantly reduced (p=0.008), while aortic tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix metalloproteinase (MMP-12) was reduced in T3–4 mg/kg compared to T3-negative rabbits group (0.2±0.1 vs. 28.5±3.1%; 3.0±1.6 vs. 14.0±1.7%; and 5.2±2.2 vs. 27.7±0.8%, respectively, p<0.05). T3–15 mg/kg group showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9±1.9 vs. 28.5±3.1%; 10.3±0.5 vs. 59.8±8.5%; 2.6±1.7 vs. 14.0±1.7%; and 16.2±3.2 vs. 27.7 0.8%, respectively, p<0.05). In B2, T3–4 mg/kg group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12 and MMP-9 compared to T3-negative rabbits group (29.9±2.4 vs. 55.3±1.3%; 26.7±1.5 vs. 60.5±7.6%; 15.7±0.7 vs. 27.7±4.8%; 34.8±2.7 vs. 46.5±3.4%; and 25.89±3.9 vs. 45.9±1.7%, respectively, p<0.05). T3–15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5±3.3 vs. 35.6±2.5%; 24.9±1.3 vs. 55.3±1.3%; 29.9±6.7 vs. 60.5±7.6; 11.3±2.2 vs. 27.7±4.8%; 23.0±1.7 vs. 46.5±3.4%; and 17.6±1.9 vs. 45.9±1.7%, respectively, p<0.05. Conclusion: These findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation to standard treatment in the prevention of CAD

Hepatitis B virus infection: Epidemiology and seroprevalence rate amongst negrito tribe in Malaysia

Introduction: Prevalence of Hepatitis B virus (HBV) infection among the non-indigenous people in Malaysia has been well established and range between 3% and 5%. However, data from the indigenous (Orang Asli) people is still lacking. The Negrito population is the most remotely located Orang Asli tribe with limited access to health care facilities. This study was undertaken to determine the epidemiology and seroprevalence of HBV infection among the Negrito. Methods: Surveys were conducted in five Negrito settlements in Kelantan and Perak states in Malaysia. A total of 150 participants were recruited. Clinical history was taken and physical examination was performed. Five millilitres of whole blood were collected and tested for hepatitis B surface antigen (HBsAg) using electrochemiluminescence immunoassay. Results: Participants were mainly from the Bateq (49.3%) and Mendriq (29.4%) sub-tribes. Overall, 13 subjects (8.7 %); nine males and four females were HBsAg positive. Nine of the HBsAg positive subjects were ≥35 years old. All of them had history of home deliver without evidence of antenatal record. Six (46%) of the HBsAg positive subjects had tattoo and body piercing in the past. Conclusion: The prevalence of HBV infection rate amongst the Negrito tribe is almost three-fold compared to the national rates. The reason for this finding remains unclear. Tattooing, body piercing and vertical transmission could be the main possible routes of transmission of HBV among the Negrito population in Malaysia. © 2019, Malaysian Medical Association. All rights reserved

EFFECTS OF PALM OIL DERIVED TOCOTRIENOL RICH FRACTION AND VITAMIN E ISOMERS ON BIOMARKERS OF EARLY ATHEROGENESIS IN STIMULATED HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

This study was conducted to investigate the effects of tocotrienol rich fraction (TRF), α-TOC, and pure TCT isomers (α-. γ- & δ-TCT) on inflammation, endothelial activation, nuclear factor kappa B (NFκB), endothelial nitric oxide synthase (eNOS) and monocyte binding activity (MBA) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of α-TOC, pure TCT isomers and TRF (0.3-10 µM) together with lipopolysaccharides (LPS) for 16 h. Culture medium and cells were collected and measured for the protein and gene expression of IL-6, TNF-α, NFκB, ICAM-1, VCAM1, e-selectin, and eNOS. Monocyte binding activity (MBA) was measured by Rose Bengal staining. Area under the curve (AUC) analysis revealed that TRF and pure TCT particularly γ- and δ- isomers, showed better inhibition of inflammation and endothelial activation, MBA and greater eNOS increment than α-TOC. These suggest that TRF and pure TCT isomers have potential as preventive anti-atherogenic agents by attenuating the release of early biomarkers of atherogenesis which is better than α-TOC in LPS-stimulated human endothelial cells

Comparable Enhanced Prothrombogenesis in Simple Central Obesity and Metabolic Syndrome

Objective. There is limited data comparing prothrombogenic or fibrinolysis biomarkers (tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)) simultaneously in subjects with Metabolic Syndrome (MS), simple central obesity without MS (COB) and normal controls (NC). We investigated the concentrations of fibrinolysis biomarkers in subjects with MS, COB and NC. Methods. A cross-sectional study involving 503 drug naive subjects (163 males, aged 30–65 years old (mean age ± SD = 47.4 ± 8.3 years)) divided into MS, COB and NC groups. COB was defined as central obesity (waist circumference (WC) males ≥90 cm, females ≥80 cm) in the absence of MS according to the International Diabetes Federation 2006. Fasting blood levels of tPA and PAI-1were analyzed. Results. MS and COB had significantly higher concentration of all biomarkers compared to NC. The MS group had significantly higher concentration of tPA and PAI-1 compared to COB. WC and HDL-c had significant correlation with all biomarkers (tPA p<0.001, PAI-1 p<0.001). Fasting plasma glucose and diastolic blood pressure were independent predictors after correcting for confounding factors. Conclusion. Central obesity with or without MS both demonstrated enhanced prothrombogenesis. This suggests that simple obesity possibly increases the risk of coronary artery disease in part, via increased susceptibility to thrombogenesis