Potential Metabolite Biomarkers for Acute Versus Chronic Stage of Ischemic Stroke: A Pilot Study.

BACKGROUND: Metabolome profiling is used to identify biomarkers for acute ischemic stroke (AIS). Previous studies compared metabolite profiles in AIS and healthy controls, which did not account for factors that affect metabolome (genetics, medications). This pilot project evaluates the change in metabolite concentrations between the acute and chronic stage of stroke in the same cohort in order to minimize other factors impact. METHODS: We performed global metabolome profile on serum of 20 and urine of 12 stroke patients in acute (72 hours) and chronic (3-5.2 months) stage and compared relative peak values using Wilcoxon and orthogonal partial least squares discriminant analysis methods. Chronic stage metabolite concentrations were considered baseline. We performed analysis to identify significantly overrepresented pathways using MetaboAnalyst. RESULTS: Three serum metabolites asparagine (P = .045), tyrosine (P = .015), and xylose (P = .003) had significantly higher concentrations in acute stage. Seven out of top 10 serum metabolites ranked by Wilcoxon test P value were related to amino acid (AA) metabolism. Two urine metabolites glycine (P = .03) and acetylcarnitine (P = .05) had significantly different concentrations in the acute stage. Five of the top 10 urine metabolites related to AA metabolism. We identified 6 significant pathways after false discovery rate correction that were upregulated in the acute stage: (1) Aminoacyl-tRNA synthesis, (2) nitrogen, (3) alanine, aspartate, and glutamate, (4) branched-chain AA, (5) arginine and proline, and (6) phenylalanine metabolism. CONCLUSION: Longitudinal study design confirms that AA metabolism heavily involved in the pathophysiology of acute brain ischemia. Prospective longitudinal studies with a higher number of participants are needed to establish useful stroke biomarkers.

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents.

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood-based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA-IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.

Grain and sweet sorghum (Sorghum bicolor L. Moench) serves as a novel source of bioactive compounds for human health.

Grain sorghum is an important staple food crop grown globally while sweet sorghum is increasingly considered as a promising biofuel feedstock. Biofuels are the major economic products from the processing of large quantities of biomass, which is currently being utilized to make value-added products in the biorefinery approach. To date, these value-added products are typically commodity chemicals and waste materials used in agriculture. However, there are opportunities to generate high-value bioactive compounds from sorghum grain and biomass. Chronic diseases, such as cancers, are the top causes for morbidity and mortality in developed nations and are promoted by inflammation and oxidative stress. Globally, colorectal cancer results in approximately one-half million deaths annually. It is estimated that as much as 80% of colorectal cancer cases can be attributed to environmental and dietary factors. The sorghum grain and ligno-cellulosic biomass generated for biofuel production has been reported to be high in bioactive compounds, including phenolic acids and flavonoids, with antioxidant and anti-inflammatory properties. This review focuses on the bioactive compounds of grain and sweet sorghum (Sorghum bicolor L. Moench), for their anti-inflammatory, antioxidant, anti-colon cancer, and immune modulator functions. The review summarizes previous efforts to identify and quantify bioactive compounds in sorghum and documents their anti-cancer biological activities. Finally, this review discusses bioactive compound extraction methodologies and technologies as well as considerations for incorporating these technologies into current biorefining practices.

Children with Crohn's Disease Frequently Consume Select Food Additives.

OBJECTIVE: Certain food additives may promote the pathogenesis of Crohn's disease (CD), but thus far the evaluation of food additive exposures in humans has been limited. The objective of this study was to quantify food additive exposures in children with CD. METHODS: In a trial for bone health in CD, children were followed over 24 months with evaluation of disease characteristics, dietary intake, and body composition. At baseline, participants completed three 24-h dietary recalls. Foods were categorized, and the ingredient list for each item was evaluated for the presence of select food additives: polysorbate-80, carboxymethylcellulose, xanthan gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposures to these food additives was described for study participants and for food categories. RESULTS: At study baseline, 138 participants, mean age 14.2 ± 2.8 years, 95% having inactive or mild disease, were enrolled and dietary recalls were collected. A total of 1325 unique foods were recorded. Mean exposures per day for xanthan gum was 0.96 ± 0.72, carrageenan 0.58 ± 0.63, maltodextrin 0.95 ± 0.77, and soy lecithin 0.90 ± 0.74. The other additives had less than 0.1 exposures per day. For the 8 examined food additives, participants were exposed to a mean (SD) of 3.6 ± 2.1 total additives per recall day and a mean (SD) of 2.4 ± 1.0 different additives per day. CONCLUSION: Children with CD frequently consume food additives, and the impact on disease course needs further study.

Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.

The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.

Ancient Thali Diet: Gut Microbiota, Immunity, and Health.

Diet provides macronutrients (carbohydrates, proteins, and fats), micronutrients (vitamins and minerals), and phytochemicals (non-nutrient bioactive compounds). Emerging evidence suggests that above dietary components can directly impact the composition and metabolic activity of the mammalian gut microbiota and in turn, affect both physical and mental health. There is a growing recognition that rise in chronic disease burden in Western countries may due to progressive loss of beneficial bacteria and microbial diversity. This perspective explores the possibility of using Indian thali, an ancient approach to diet that provides both fiber and different phytochemicals by incorporating a variety of plant foods in different colors. This variety helps to restore diversity in the gut bacteria and may potentially prevent or reverse chronic disease, such as colon cancer or type 2 diabetes.

Comparison of rumen bacterial communities in dairy herds of different production.

BACKGROUND: The purpose of this study was to compare the rumen bacterial composition in high and low yielding dairy cows within and between two dairy herds. Eighty five Holstein dairy cows in mid-lactation (79-179 days in milk) were selected from two farms: Farm 12 (M305 = 12,300 kg; n = 47; 24 primiparous cows, 23 multiparous cows) and Farm 9 (M305 = 9700 kg; n = 38; 19 primiparous cows, 19 multiparous cows). Each study cow was sampled once using the stomach tube method and processed for 16S rRNA gene amplicon sequencing using the Ion Torrent (PGM) platform. RESULTS: Differences in bacterial communities between farms were greater (Adonis: R2 = 0.16; p < 0.001) than within farm. Five bacterial lineages, namely Prevotella (48-52%), unclassified Bacteroidales (10-12%), unclassified bacteria (5-8%), unclassified Succinivibrionaceae (1-7%) and unclassified Prevotellaceae (4-5%) were observed to differentiate the community clustering patterns among the two farms. A notable finding is the greater (p < 0.05) contribution of Succinivibrionaceae lineages in Farm 12 compared to Farm 9. Furthermore, in Farm 12, Succinivibrionaceae lineages were higher (p < 0.05) in the high yielding cows compared to the low yielding cows in both primiparous and multiparous groups. Prevotella, S24-7 and Succinivibrionaceae lineages were found in greater abundance on Farm 12 and were positively correlated with milk yield. CONCLUSIONS: Differences in rumen bacterial populations observed between the two farms can be attributed to dietary composition, particularly differences in forage type and proportion in the diets. A combination of corn silage and alfalfa silage may have contributed to the increased proportion of Proteobacteria in Farm 12. It was concluded that Farm 12 had a greater proportion of specialist bacteria that have the potential to enhance rumen fermentative digestion of feedstuffs to support higher milk yields.

Food systems approach to cancer prevention.

New cancer cases are expected to surge 57% worldwide in the next two decades. The greatest burden will be in low- and middle-income countries that are ill equipped to face this epidemic. Similarly, in the United States, low-income populations are at greater risk for cancer. As most cancers contain over 50 genetic alterations, and as these alterations define dysregulation of over 10 different critical cellular signaling pathways, a "silver bullet" treatment is not effective against most cancers. Instead, the latest World Cancer Report (2012) suggests a research shift toward developing prevention strategies for cancer. Accumulating evidence suggests that a diet high in plant-based foods is preventive of a variety of chronic diseases, including cancer. A plethora of bioactive compounds-such as polyphenols, glucosinolates and carotenoids in fruits, vegetables, grains, and legumes-are shown to suppress a variety of biological capabilities required for tumor growth. While much research has shown that plant bioactive compounds can suppress sustained proliferative signaling, angiogenesis, and metastasis, as well as promote cancer stem cell apoptosis, public health campaigns to increase fruit and vegetable consumption have, overall, been less effective than desired. Thus, there is a need for innovative strategies to support increased consumption of bioactive compounds for cancer prevention particularly in vulnerable populations. Many practices of the farm-to-fork continuum, including preharvest practices, postharvest storage, and processing and consumer practices, affect a food's bioactive compound content, composition, and chemopreventive bioactivity. Food system practices may be adjusted to reduce the toxic compound levels (e.g., glycoalkaloids in potatoes) and improve the bioactive compound profile, thus, elevate the cancer fighting properties of fruits, vegetables, and other food products. This review presents current scientific evidence outlining farm-to-fork effects on fruit and vegetable bioactive compounds in order to aid the development of new and reasonable strategies for cancer prevention.

Deficiency of stearoyl-CoA desaturase-1 aggravates colitogenic potential of adoptively transferred effector T cells.

Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially reduced oleate in cell membranes. An altered SCD1 level was observed during intestinal inflammation; however, its role in modulating inflammatory bowel disease remains elusive. Herein, we investigated the colitogenic capacity of Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model. Splenic effector T cells (CD4+CD25-) from age- and sex-matched wild-type (WT) and Scd1KO mice were isolated by FACS and intraperitoneally administered to Rag1KO mice, which were monitored for the development of colitis. At day 60 postcell transfer, Rag1KO mice that received Scd1KO CD4+CD25- T cells displayed accelerated and exacerbated colitis than mice receiving WT CD4+CD25- T cells. Intriguingly, Scd1KO CD4+CD25- T cells display augmented inflammatory cytokine profile and cellular membrane fluidity with a concomitant increase in proinflammatory saturated fatty acids, which we postulate to potentially underlie their augmented colitogenic potential.

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

BACKGROUND: Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. METHODS: After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. RESULTS: Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. CONCLUSIONS: eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Grape compounds suppress colon cancer stem cells in vitro and in a rodent model of colon carcinogenesis.

BACKGROUND: We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known. METHODS: We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo. RESULTS: RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear ß-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of ß-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/ß-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE. CONCLUSION: The suppression of Wnt/ß-catenin signaling and elevated mitochondrial-mediated apoptosis in colon CSCs support potential clinical testing/application of grape bioactives for colon cancer prevention and/or therapy.

The intestinal metabolome: an intersection between microbiota and host.

Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person's physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, the computational challenges in integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future data sets.

Mitigation of obesity-promoted diseases by Nigella sativa and thymoquinone.

Obesity is closely associated with increased incidence of cardiovascular diseases, cancer, insulin resistance, and immune dysfunction, and thus obesity-mitigation strategies should take into account these secondary pathologies in addition to promoting weight loss. Recent studies indicate that black cumin (Nigella sativa) has cardio-protective, anti-cancer, anti-diabetic, antioxidant, and immune-modulatory properties. While black cumin and/or its major bioactive constituent, thymoquinone have demonstrated bioactivity in a variety of disease models, the mechanisms of action are largely unknown. Given the growing interest in and the use of functional foods and nutraceuticals, as well as the increase in obesity and chronic diseases worldwide, further research into the therapeutic/preventive effects of black cumin may be beneficial.

Comparative effects of vacuum or conventional frying on the polyphenol chemistry and in vitro colon cancer stem cell inhibitory activity of purple-flesh potatoes.

Potatoes are an important food crop that undergo postharvest storage, reconditioning, and cooking. Colored-flesh varieties of potatoes are rich in phenolic acids and anthocyanins. Previous studies have suggested that purple-flesh potatoes can inhibit colon cancer cells in vitro and reduce colon carcinogenesis in vivo. Vacuum frying (VF), as an alternative to conventional frying (CF), reduces fat content and may promote polyphenol retention in potato chips. We examined the impacts of reconditioning (storing at 13°C for 3 weeks following the 90-day cold storage at 7°C) and frying method on phenolic chemistry and in vitro colon cancer stem cell (CCSC) inhibitory activity of purple-flesh potato chips. We found that reconditioned chips exhibited higher total phenolic content (TPC) than nonreconditioned chips. We found that VF chips had lower TPC than CF chips. We observed no interaction between treatments. We found that VF chips had 27% higher total monomeric anthocyanin levels than CF chips, and observed a significant interaction between treatments. We found that VF chips had higher concentrations of caffeic acid (42%-72% higher), malvidin (46%-98% higher), and pelargonidin (55%-300% higher) than CF chips. We found that reconditioning had no effect. We found that VF chips had greater in vitro CCSC inhibitory activity than CF chips. Our results suggest that VF can improve the phytochemical profile and health-related functionality of purple-flesh potato chips, but additional studies are needed to determine if these results translate to the in vivo situation. PRACTICAL APPLICATION: Our current study shows that vacuum frying of purple-flesh potato chips results in higher levels of total monomeric anthocyanins and concentrations of specific polyphenols as compared to chips produced by conventional frying. These differences correlated with better in vitro colon cancer stem cell inhibitory activity. Although additional in vivo studies are needed, our current results suggest that it may be possible for potato processors to improve the health-related functionality of purple-flesh potato chips through the use of vacuum frying.

Resveratrol suppresses human colon cancer cell proliferation and induces apoptosis via targeting the pentose phosphate and the talin-FAK signaling pathways-A proteomic approach.

BACKGROUND: We and others have previously reported that resveratrol (RSV) suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or in vivo, however molecular mechanisms are not fully elucidated. Particularly, little information is available on RSV's effects on metabolic pathways and the cell-extra cellular matrix (ECM) communication that are critical for cancer cell growth. To identify important targets of RSV, we analyzed whole protein fractions from HT-29 advanced human colon cancer cell line treated with solvent control, IGF-1 (10 nM) and RSV (150 µM) using LC/MS/MS-Mud PIT (Multidimensional Protein Identification Technology). RESULTS: Pentose phosphate pathway (PPP), a vital metabolic pathway for cell cycle progression, was elevated and suppressed by IGF-1 and RSV, respectively in the HT-29 cell line. Enzymatic assays confirmed RSV suppression of glucose-6 phosphate dehydrogenase (rate limiting) and transketolase, key enzymes of the PPP. RSV (150 µM) suppressed, whereas IGF-1 (10 nM) elevated focal adhesion complex (FAC) proteins, talin and pFAK, critical for the cell-ECM communication. Western blotting analyses confirmed the suppression or elevation of these proteins in HT-29 cancer cells treated with RSV or IGF-1, respectively. CONCLUSIONS: Proteomic analysis enabled us to establish PPP and the talin-pFAK as targets of RSV which suppress cancer cell proliferation and induce apoptosis in the colon cancer cell line HT-29. RSV (150 µM) suppressed these pathways in the presence and absence of IGF-1, suggesting its role as a chemo-preventive agent even in obese condition.

Role of Gut Microbiota in the Anti-Colitic Effects of Anthocyanin-Containing Potatoes.

SCOPE: Anthocyanin-containing potatoes exert anti-inflammatory activity in colitic mice. Gut bacterial dysbiosis plays a critical role in ulcerative colitis. This study examined the extent to which the anti-colitic activity of anthocyanin-containing red/purple-fleshed potatoes depends on the gut bacteria using a chemically-induced rodent model of colitis with the intact and antibiotic-ablated microbiome. METHODS AND RESULTS: Four-week-old male mice (C57BL6) are randomly assigned to the control diet or 20% purple-/red-fleshed potatoes supplemented diet group. The microbiota-ablated group received an antibiotic cocktail in drinking water. At week nine, colitis is induced by 2% dextran sulfate sodium (DSS) in drinking water for five days. Administration of antibiotics resulted in a 95% reduction in gut bacterial load and fecal SCFAs. DSS-induced elevated gut permeability and body weight loss are more pronounced in antibiotic mice compared to non-antibiotic mice. Purple- or red-fleshed potato supplementation (20% w/w) ameliorated DSS-induced reduction in colon length and mucin 2 expression levels, and increase in permeability, spleen weight, myeloperoxidase (MPO) activity, and inflammatory cytokines (IL-6, IL-17, and IL1-ß) expression levels in non-antibiotic mice, but not in gut microbiota ablated mice. CONCLUSIONS: Anthocyanin-containing potatoes are potent in alleviating colitis, and the gut microbiome is critical for the anti-colitic activity of anthocyanin-containing potatoes.

Anthocyanin-containing purple potatoes ameliorate DSS-induced colitis in mice.

Ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD), is on the rise worldwide. Approximately three million people suffer from IBD in the United States alone, but the current therapeutic options (e.g., corticosteroids) come with adverse side effects including reduced ability to fight infections. Thus, there is a critical need for developing effective, safe and evidence-based food products with anti-inflammatory activity. This study evaluated the antiinflammatory potential of purple-fleshed potato using a dextran sodium sulfate (DSS) murine model of colitis. Mice were randomly assigned to control (AIN-93G diet), P15 (15% purple-fleshed potato diet) and P25 (25% purple-fleshed potato diet) groups. Colitis was induced by 2% DSS administration in drinking water for six days. The results indicated that purple-fleshed potato supplementation suppressed the DSS-induced reduction in body weight and colon length as well as the increase in spleen and liver weights. P15 and P25 diets suppressed the elevation in the intestinal permeability, colonic MPO activity, mRNA expression and protein levels of pro-inflammatory interleukins IL-6 and IL-17, the relative abundance of specific pathogenic bacteria such as Enterobacteriaceae, Escherichia coli (E. coli) and pks+ E. coli, and the increased flagellin levels induced by DSS treatment. P25 alone suppressed the elevated systemic MPO levels in DSS-exposed mice, and elevated the relative abundance of Akkermansia muciniphila (A. muciniphila) as well as attenuated colonic mRNA expression level of IL-17 and the protein levels of IL-6 and IL-1ß. Therefore, the purple-fleshed potato has the potential to aid in the amelioration of UC symptoms.

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways.

BACKGROUND: Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. METHODS: We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. RESULTS: Resveratrol (100-150 microM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. CONCLUSIONS: For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a chemotherapeutic agent.

The bioactive compounds alpha-chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells.

We recently reported that colored potato extracts and an anthocyanin rich fraction suppressed lymph-node carcinoma of the prostate (LNCaP) and prostate cancer-3 (PC-3) prostate cancer cell proliferation and induced apoptosis via caspase-dependent and caspase-independent pathways. Chlorogenic acid, caffeic acid, gallic acid, catechin, malvidin, and glycoalkaloids (alpha-chaconine and solanine) have now been identified as the major bioactive components of potato, and their effects on LNCaP and PC-3 cell proliferation and apoptosis have been investigated. alpha-chaconine (5 microg/ml) and gallic acid (15 microg/ml) exhibited potent antiproliferative properties and increased cyclin-dependent kinase inhibitor p27 levels in both cell lines. Both alpha-chaconine and gallic acid induced poly [adenosine diphosphate (ADP)] ribose polymerase cleavage and caspase-dependent apoptosis in LNCaP cells; however, caspase-independent apoptosis through nuclear translocation of endonuclease G was observed in both LNCaP and PC-3 cells. alpha-chaconine and gallic acid activated c-Jun N-terminal protein kinase (JNK), and this response played a major role in induction of caspase-dependent apoptosis in LNCaP cells; whereas modulation of JNK and mitogen-activated protein kinase did not affect alpha-chaconine- and gallic acid-induced caspase-independent apoptosis. These results suggest that apoptosis induced by whole potato extracts in prostate cancer cell lines may be in part due to alpha-chaconine and gallic acid.