Advances in "omics"-based fields have produced an explosion of new information, fueling high expectations for improved public and individualized health. Unfortunately, there exists a widening gap between basic biochemistry and "omics"-based population research, with both disciplines failing to translate their full potential impact to human health applications. A paucity of comprehensive study systems is one of the many roadblocks faced by translational research today. This commentary will highlight the current status of such research, particularly emphasizing the role of nutrigenomics.
Triptolide is a diterpene triepoxide present in roots of Tripterygium wilfordii Hook F., with known anti‐inflammatory, immunosuppressive and anti‐cancer properties. Although it is known that triptolide inhibits NFκB activation downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. Objective of the study was to investigate if triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. The results suggest that the suppression of agonist‐induced NFκB activation and chemokine expression by triptolide is mediated by targeting the early signaling of TLRs, particularly that of TLR4 in RAW 264.7 cells. Triptolide down regulated the expression of TLR4 proteins and that of TRIF adapter proteins in MyD88‐independent pathway of TLR4. In addition gene expression profiles in response to triptolide treatment suggest that triptolide may have multiple cellular targets contributing to its strong anti‐inflammatory and immune suppressive properties. This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may down regulate NFκB activation during inflammatory conditions. Funding for this research came from multiple grants by National Institutes of Health, Bethesda, MD [to MD and IR] and in parts by Phytomedics Inc., Jamesburg, NJ [to IR].
A metabolic health crisis is well recognized as cardiovascular diseases remain the leading cause of mortality. Effects of RS4, a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of resistant starch type‐4 (RS4)‐enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double‐blind, placebo‐controlled, cluster crossover intervention (n=86, age蠅18, 2 12‐week interventions), individuals were classified as having MetS (With‐MetS) or not having MetS (No‐MetS) following IDF criteria. RS4 consumption compared with CF resulted in 7.2% (p=0.002) lower mean total cholesterol (TC), 5.5% (p=0.04) lower non‐HDL, and a 12.8% (p<0.001) lower HDL cholesterol in the With‐MetS group. Individuals in the No‐MetS group had a 2.6% (p=0.02) smaller waist circumference and 1.5% (p=0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1% increase in fat‐free mass also was observed in all participants combined (p=0.02). No significant effect of RS4 was observed for glycemic variables and blood pressure. RS4 consumption improved dyslipidemia and body composition. Functional and adaptable prebiotic food ingredients such as RS4 could be an effective strategy for public metabolic and cardiovascular health promotion. NCT01887964 at clinicaltrials.gov. Grant Funding Source : Funding from MGP Ingredients, Atchison KS (# 3P2662), SDAES (#AH360) to MD , EAM to BS
Abstract Isothiocyanates (ITCs), prevalent in cruciferous vegetables, are known for their anticarcinogenic properties. Prior research has indicated that heparin can stimulate the growth of colon cancer cells. However, the implications of ITCs in the diet of cancer patients receiving heparin‐based therapies have yet to be fully understood. This exploratory in vitro study examines the proliferative effects of low‐molecular‐weight heparin (LMWH) on human colon cancer cells and assesses the antiproliferative potential of four ITC compounds, exploring possible epidermal growth factor family of receptor tyrosine kinases (Erb‐B) related mechanisms. We evaluated cell viability in HCT‐116 and HT‐29 cell lines following treatment with ITCs alone or combined with LMWH (20 μg/mL) at various concentrations (1–100 μM). Clonogenic and wound‐healing assays were performed after 24 h of treatment with 5 μM ITCs. Additionally, messenger RNA (mRNA) and protein expression of Erb‐B family genes was measured using quantitative polymerase chain reaction (qPCR) and Western blotting. Statistical analysis was conducted using analysis of variance (ANOVA) with Dunnett's post hoc test. Results indicated that the half‐maximal inhibitory concentration (IC 50 ) values for Phenylethyl isothiocyanate (PEITC), Benzyl isothiocyanate (BITC), and Sulforaphane (SFN) were lower than those of Allyl isothiocyanate (AITC) in LMWH‐stimulated HCT‐116 (20.77, 19.10, and 44.05 μM, respectively) and HT‐29 (74.94, 26.77, and 43.49 μM, respectively). PEITC and SFN significantly reduced ErbB1 (epidermal growth factor receptor (EGFR)) and ErbB4 (receptor tyrosine‐protein kinase erbB‐4) expression, while BITC decreased ErbB2 (receptor tyrosine‐protein kinase erbB‐2) and transforming growth factor beta (TGF‐ β ) expression in HCT‐116 cells (all, p < .05). PEITC, BITC, and SFN also increased proapoptotic Bax expression and decreased the antiapoptotic B‐cell lymphoma 2 (Bcl‐2) expression (all, p < .05). These findings suggest that specific ITCs may mitigate cancer cell proliferation induced by LMWH in cancer therapies, highlighting their potential therapeutic efficacy.
Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Nonpolar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications), whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1beta and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes.
Trimethylamine-N-oxide (TMAO) is a microbiota-dependent and primarily animal-protein-derived proatherogenic metabolite. The ecological impact of pork-the most popular animal protein worldwide-on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart-healthier animal protein, we investigated-if pork intake results in inferior-to-chicken TMAO-response while consuming a diet based on the Dietary Guidelines for Americans (DGA).In a randomized, controlled, all-food-provided, crossover, feeding trial, healthy adults consumed 156 g day-1 of lean-pork or chicken (active-control) as primary proteins. Mixed-effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota-generated essential TMAO-precursor-trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L-carnitine, composition and functional-capability of the microbiota, and association of baseline TMAO-levels with TMAO-response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic-amine signatures postdiet in both groups indicate a background DGA-effect.Unlike extrapolating negative results, this study presents noninferiority-testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA-diet does not exacerbate TMAO-response. Results highlight the importance of understanding protein-TMAO interactions within dietary patterns.
Phenethylisothiocyanate (PEITC) is produced by Brassica food plants. PEO is a PEITC Essential Oil containing >95% natural PEITC. PEITC is known to produce various health benefits but its effect in alleviation of ulcerative colitis signs is unknown.In two efficacy studies (acute and chronic) oral administration of PEO was effective at remitting acute and chronic signs of ulcerative colitis (UC) in mice. Disease activity, histology and biochemical characteristics were measured in the treated animals and were compared with appropriate controls. PEO treatment significantly improved body weights and stool consistency as well as decreased intestinal bleeding. PEO treatment also reduced mucosal inflammation, depletion of goblet cells and infiltration of inflammatory cells. Attenuation of proinflammatory interleukin1beta production was observed in the colons of PEO-treated animals. Expression analyses were also carried out for immune function related genes, transcription factors and cytokines in lipopolysaccharide-activated mouse macrophage cells. PEO likely affects an intricate network of immune signaling genes including a novel concentration dependent reduction of total cellular Signal Transducer and Activator of Transcription 1 (STAT1) as well as nuclear phosphorylated-STAT1 (activated form of STAT1). A PEO-concentration dependent decrease of mRNA of C-X-C motif ligand 10 (a STAT1 responsive chemokine) and Interleukin 6 were also observed.PEO might be a promising candidate to develop as a treatment for ulcerative colitis patients. The disease attenuation by PEO is likely associated with suppression of activation of STAT1 transcription and inhibition of pro-inflammatory cytokines.
Overweight and obesity are global health problems that contribute to the rising prevalence of non-communicable diseases, such as type 2 diabetes, heart disease, and certain cancers. The World Health Organization recognizes obesity as a primarily diet-induced, preventable condition, yet losing weight or keeping weight loss permanent is a universal challenge. In the U.S., formal dietary guidelines have existed since 1980. Over the same time-period, the incidence of obesity has skyrocketed. Here, we present our perspective on why current dietary guidelines are not always supported by a robust body of scientific data and emphasize the critical need for accelerated nutrition research funding. A clear understanding of the interaction of dietary patterns with system-level biological changes in a precise, response-specific manner can help inform evidence-based nutrition education, policy, and practice.
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