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Fulltext A randomized, double-blind, placebo-controlled, clinical trial on probiotic soy milk and soy milk: effects on epigenetics and oxidative stress in patients with type II diabetes

Hariri M, Salehi R, Feizi A, Mirlohi M, Ghiasvand R, Habibi N

Genes Nutr, 2015 Nov;10(6):52.
PMID: 26577825 DOI: 10.1007/s12263-015-0503-1

This clinical trial aimed to discover the effects of probiotic soy milk and soy milk on MLH1 and MSH2 promoter methylation, and oxidative stress among type II diabetic patients. Forty patients with type II diabetes mellitus aged 35-68 years were assigned to two groups in this randomized, double-blind, controlled clinical trial. Patients in the intervention group consumed 200 ml/day of probiotic soy milk containing Lactobacillus plantarum A7, while those in the control group consumed 200 ml/d of conventional soy milk for 8 weeks. Fasting blood samples, anthropometric measurements, and 24-h dietary recalls were collected at the baseline and at the end of the study, respectively. Probiotic soy milk significantly decreased promoter methylation in proximal and distal MLH1 promoter region (P 0.05). The consumption of probiotic soy milk improved antioxidant status in type II diabetic patients and may decrease promoter methylation among these patients, indicating that probiotic soy milk is a promising agent for diabetes management.
Fulltext Tocotrienols and breast cancer: the evidence to date

Nesaretnam K, Meganathan P, Veerasenan SD, Selvaduray KR

Genes Nutr, 2012 Jan;7(1):3-9.
PMID: 21516480 DOI: 10.1007/s12263-011-0224-z

Breast cancer is the second most frequent cancer affecting women worldwide after lung cancer. The toxicity factor associated with synthetic drugs has turned the attention toward natural compounds as the primary focus of interest as anticancer agents. Vitamin E derivatives consisting of the well-established tocopherols and their analogs namely tocotrienols have been extensively studied due to their remarkable biological properties. While tocopherols have failed to offer protection, tocotrienols, in particular, α-, δ-, and γ-tocotrienols alone and in combination have demonstrated anticancer properties. The discovery of the antiangiogenic, antiproliferative, and apoptotic effects of tocotrienols, as well as their role as an inducer of immunological functions, not only reveals a new horizon as a potent antitumor agent but also reinforces the notion that tocotrienols are indeed more than antioxidants. On the basis of a transcriptomic platform, we have recently demonstrated a novel mechanism for tocotrienol activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicate a high affinity of specific forms of tocotrienols for ERβ, but not for ERα. Moreover, we have demonstrated that specific tocotrienols increase ERβ translocation into the nucleus which, in turn, activates the expression of estrogen-responsive genes (MIC-1, EGR-1 and Cathepsin D) in breast cancer cells only expressing ERβ cells (MDA-MB-231) and in cells expressing both ER isoforms (MCF-7). The binding of specific tocotrienol forms to ERβ is associated with the alteration of cell morphology, caspase-3 activation, DNA fragmentation, and apoptosis. Furthermore, a recently concluded clinical trial seems to suggest that tocotrienols in combination with tamoxifen may have the potential to extend breast cancer-specific survival.
Fulltext Microarray analysis revealed different gene expression patterns in HepG2 cells treated with low and high concentrations of the extracts of Anacardium occidentale shoots

Khaleghi S, Aziz AA, Razali N, Junit SM

Genes Nutr, 2011 Nov;6(4):413-27.
PMID: 21484159 DOI: 10.1007/s12263-011-0216-z

In this study, the effects of low and high concentrations of the Anacardium occidentale shoot extracts on gene expression in liver HepG2 cells were investigated. From MTT assays, the concentration of the shoot extracts that maintained 50% cell viability (IC(50)) was 1.7 mg/ml. Cell viability was kept above 90% at both 0.4 mg/ml and 0.6 mg/ml of the extracts. The three concentrations were subsequently used for the gene expression analysis using Affymetrix Human Genome 1.0 S.T arrays. The microarray data were validated using real-time qRT-PCR. A total of 246, 696 and 4503 genes were significantly regulated (P
Fulltext Gene regulation in β-sitosterol-mediated stimulation of adipogenesis, glucose uptake, and lipid mobilization in rat primary adipocytes

Chai JW, Lim SL, Kanthimathi MS, Kuppusamy UR

Genes Nutr, 2011 May;6(2):181-8.
PMID: 21484150 DOI: 10.1007/s12263-010-0196-4

The nutraceutical benefits of β-sitosterol (SIT) are well documented. The present study investigated the in vitro effects of SIT on adipogenesis, glucose transport, and lipid mobilization in rat adipocytes. Primary cultures of rat preadipocytes and differentiated adipocytes were used in this study. Glucose uptake was measured by the uptake of radio-labeled glucose. Adipogenesis and lipolysis were measured by oil-red-O and glycerol quantification methods, respectively. The expression of protein kinase B (Akt), glucose transporter 4 (GLUT4), hormone sensitive lipase (HSL), and phosphatidylinositol-3-kinase (PI3 K) genes in SIT-treated adipocytes were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). The data showed that SIT induced glucose uptake in adipocytes. It also stimulated adipogenesis in differentiating preadipocytes. Interestingly, although SIT displayed general insulin-mimetic activity by stimulating glucose uptake and adipogenesis, it also induced lipolysis in adipocytes. Furthermore, the SIT-induced lipolysis was not attenuated by insulin and co-incubation of SIT with epinephrine improved epinephrine-induced lipolysis. GLUT4 gene expression was highly down-regulated in SIT-treated adipocytes, compared to insulin-treated adipocytes, which was up-regulated. Insulin- and SIT-treated adipocytes showed similar levels of Akt, HSL, and PI3 K gene down-regulation. These observations suggest that the elevation of glucose uptake in SIT-treated adipocytes was unrelated to de novo synthesis of GLUT4 and the SIT-induced lipolysis is associated with the down-regulation of Akt and PI3K genes. The unique effects of SIT on the regulation of glucose uptake, adipogenesis, and lipolysis in adipocytes show that it has potential to be utilized in diabetes and weight management.
Fulltext Unleashing the untold and misunderstood observations on vitamin E

Gee PT

Genes Nutr, 2011 Feb;6(1):5-16.
PMID: 21437026 DOI: 10.1007/s12263-010-0180-z

Paradoxically, meta-analysis of human randomized controlled trials revealed that natural but not synthetic α-tocopherol supplementation significantly increases all-cause mortality at 95% confidence interval. The root cause was that natural α-tocopherol supplementation significantly depressed bioavailability of other forms of vitamin E that have better chemo-prevention capability. Meta-analysis outcome demonstrated flaws in the understanding of vitamin E. Reinterpretation of reported data provides plausible explanations to several important observations. While α-tocopherol is almost exclusively secreted in chylomicrons, enterocytes secrete tocotrienols in both chylomicrons and small high-density lipoproteins. Vitamin E secreted in chylomicrons is discriminately repacked by α-tocopherol transfer protein into nascent very low-density lipoproteins in the liver. Circulating very low-density lipoproteins undergo delipidation to form intermediate-density lipoproteins and low-density lipoproteins. Uptake of vitamin E in intermediate-density lipoproteins and low-density lipoproteins takes place at various tissues via low-density lipoproteins receptor-mediated endocytosis. Small high-density lipoproteins can deliver tocotrienols upon maturation to peripheral tissues independent of α-tocopherol transfer protein action, and uptake of vitamin E takes place at selective tissues by scavenger receptor-mediated direct vitamin E uptake. Dual absorption pathways for tocotrienols are consistent with human and animal studies. α-Tocopherol depresses the bioavailability of α-tocotrienol and has antagonistic effect on tocotrienols in chemo-prevention against degenerative diseases. Therefore, it is an undesirable component for chemo-prevention. Future research directions should be focused on tocotrienols, preferably free from α-tocopherol, for optimum chemo-prevention and benefits to mankind.
Fulltext Gene expression profiles in human HepG2 cells treated with extracts of the Tamarindus indica fruit pulp

Razali N, Aziz AA, Junit SM

Genes Nutr, 2010 Dec;5(4):331-41.
PMID: 21189869 DOI: 10.1007/s12263-010-0187-5

Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the family of Leguminosae. The fruit pulp had been reported to have antioxidant activities and possess hypolipidaemic effects. In this study, we attempted to investigate the gene expression patterns in human hepatoma HepG2 cell line in response to treatment with low concentration of the fruit pulp extracts. Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the study. Microarray data were validated using semi-quantitative RT-PCR and real-time RT-PCR. Amongst the significantly up-regulated genes were those that code for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5 and MTTP genes were also significantly regulated that could be linked to hypolipidaemic activities of the T. indica fruit pulp.
Hepatic transcriptome implications for palm fruit juice deterrence of type 2 diabetes mellitus in young male Nile rats

Leow SS, Bolsinger J, Pronczuk A, Hayes KC, Sambanthamurthi R

Genes Nutr, 2016;11:29.
PMID: 27795741

BACKGROUND: The Nile rat (NR, Arvicanthis niloticus) is a model of carbohydrate-induced type 2 diabetes mellitus (T2DM) and the metabolic syndrome. A previous study found that palm fruit juice (PFJ) delayed or prevented diabetes and in some cases even reversed its early stages in young NRs. However, the molecular mechanisms by which PFJ exerts these anti-diabetic effects are unknown. In this study, the transcriptomic effects of PFJ were studied in young male NRs, using microarray gene expression analysis.
METHODS: Three-week-old weanling NRs were fed either a high-carbohydrate diet (%En from carbohydrate/fat/protein = 70:10:20, 16.7 kJ/g; n = 8) or the same high-carbohydrate diet supplemented with PFJ (415 ml of 13,000-ppm gallic acid equivalent (GAE) for a final concentration of 5.4 g GAE per kg diet or 2.7 g per 2000 kcal; n = 8). Livers were obtained from these NRs for microarray gene expression analysis using Illumina MouseRef-8 Version 2 Expression BeadChips. Microarray data were analysed along with the physiological parameters of diabetes.
RESULTS: Compared to the control group, 71 genes were up-regulated while 108 were down-regulated in the group supplemented with PFJ. Among hepatic genes up-regulated were apolipoproteins related to high-density lipoproteins (HDL) and genes involved in hepatic detoxification, while those down-regulated were related to insulin signalling and fibrosis.
CONCLUSION: The results obtained suggest that the anti-diabetic effects of PFJ may be due to mechanisms other than an increase in insulin secretion.
Fulltext Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation

Razak AM, Khor SC, Jaafar F, Karim NA, Makpol S

Genes Nutr, 2018;13:31.
PMID: 30519366 DOI: 10.1186/s12263-018-0618-2

Background: Several muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 μg/mL TRF for 24 h before and after inducing differentiation.
Results: The fusion index and myotube surface area were higher (p
Fulltext Predictors of stakeholders' intention to adopt nutrigenomics

Mustapa MAC, Amin L, Frewer LJ

Genes Nutr, 2020 Sep 22;15(1):16.
PMID: 32962632 DOI: 10.1186/s12263-020-00676-y

BACKGROUND: Nutrigenomics is an emerging science that studies the relationship between genes, diet and nutrients that can help prevent chronic disease. The development of this science depends on whether the public accept its application; therefore, predicting their intention to adopt it is important for its successful implementation.
OBJECTIVE: This study aims to analyse Malaysian stakeholders' intentions to adopt nutrigenomics, and determines the factors that influence their intentions.
METHODS: A survey was conducted based on the responses of 421 adults (aged 18 years and older) and comprising two stakeholder groups: healthcare providers (n = 221) and patients (n = 200) who were located in the Klang Valley, Malaysia. The SPSS software was used to analyse the descriptive statistics of intention to adopt nutrigenomics and the SmartPLS software was used to determine the predicting factors affecting their decisions to adopt nutrigenomics.
RESULTS: The results show that the stakeholders perceived the benefits of nutrigenomics as outweighing its risks, suggesting that the perceived benefits represent the most important direct predictor of the intention to adopt nutrigenomics. The perceived risks of nutrigenomics, trust in key players, engagement with medical genetics and religiosity also predict the intention to adopt nutrigenomics. Additionally, the perceived benefits of nutrigenomics served as a mediator for four factors: perceived risks of nutrigenomics, engagement with medical genetics, trust in key players and religiosity, whilst the perceived risks were a mediator for engagement with medical genetics.
CONCLUSION: The findings of this study suggest that the intentions of Malaysian stakeholders to adopt nutrigenomics are a complex decision-making process where all the previously mentioned factors interact. Although the results showed that the stakeholders in Malaysia were highly positive towards nutrigenomics, they were also cautious about adopting it.
Palm-based tocotrienol-rich fraction (TRF) supplementation modulates cardiac sod1 expression, fxr target gene expression, and tauro-conjugated bile acid levels in aleptinemic mice fed a high-fat diet

Md Shahrulnizam NAN, Mohd Efendy Goon MD, Ab Rahim S, Lew SW, Sheikh Abdul Kadir SH, Ibrahim E

Genes Nutr, 2024 Feb 27;19(1):3.
PMID: 38413846 DOI: 10.1186/s12263-024-00742-9

Tocotrienol-rich fraction (TRF) has been reported to protect the heart from oxidative stress-induced inflammation. It is, however, unclear whether the protective effects of TRF against oxidative stress involve the activation of farnesoid X receptor (fxr), a bile acid receptor, and the regulation of bile acid metabolites. In the current study, we investigated the effects of TRF supplementation on antioxidant activities, expression of fxr and its target genes in cardiac tissue, and serum untargeted metabolomics of high-fat diet-fed mice. Mice were divided into high-fat diet (HFD) with or without TRF supplementation (control) for 6 weeks. At the end of the intervention, body weight (BW), waist circumference (WC), and random blood glucose were measured. Heart tissues were collected, and the gene expression of sod1, sod2, gpx, and fxr and its target genes shp and stat3 was determined. Serum was subjected to untargeted metabolomic analysis using UHPLC-Orbitrap. In comparison to the control, the WC of the TRF-treated group was higher (p >0.05) than that of the HFD-only group, in addition there was no significant difference in weight or random blood glucose level. Downregulation of sod1, sod2, and gpx expression was observed in TRF-treated mice; however, only sod1 was significant when compared to the HFD only group. The expression of cardiac shp (fxr target gene) was significantly upregulated, but stat3 was significantly downregulated in the TRF-treated group compared to the HFD-only group. Biochemical pathways found to be influenced by TRF supplementation include bile acid secretion, primary bile acid biosynthesis, and biotin and cholesterol metabolism. In conclusion, TRF supplementation in HFD-fed mice affects antioxidant activities, and more interestingly, TRF also acts as a signaling molecule that is possibly involved in several bile acid-related biochemical pathways accompanied by an increase in cardiac fxr shp expression. This study provides new insight into TRF in deregulating bile acid receptors and metabolites in high-fat diet-fed mice.
Fulltext Palm tocotrienols decrease levels of pro-angiogenic markers in human umbilical vein endothelial cells (HUVEC) and murine mammary cancer cells

Selvaduray KR, Radhakrishnan AK, Kutty MK, Nesaretnam K

Genes Nutr, 2012 Jan;7(1):53-61.
PMID: 21526401 DOI: 10.1007/s12263-011-0223-0

Anti-angiogenic therapy is widely being used to halt tumour angiogenesis. In this study, the anti-angiogenic activity of palm tocotrienol-rich fraction (TRF) and its individual components (γ- and δ-tocotrienol) were first investigated in vitro in human umbilical vein endothelial cells (HUVEC) and 4T1 mouse mammary cancer cells. Results showed reduced levels of Interkeukin (IL)-8 and IL-6, two pro-angiogenic cytokines in HUVEC treated with palm tocotrienols compared with α-tocopherol (α-T) and control cells (P

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