Optical Oxygen Sensor Patch Printed with Polystyrene Microparticles-based Ink on Flexible Substrate.

Optical oxygen sensors based on photoluminescence quenching have gained increasing attention as a superior method for continuous monitoring of oxygen in a growing number of applications. A simple and low-cost fabrication technique was developed to produce sensor arrays capable of two-dimensional oxygen tension measurement. Sensor patches were printed on polyvinylidene chloride film using an oxygen-sensitive ink cocktail, prepared by immobilizing Pt(II) mesotetra(pentafluorophenyl)porphine (PtTFPP) in monodispersed polystyrene microparticles. The dispersion media of the ink cocktail, high molecular weight polyvinyl pyrrolidone suspended in 50% ethanol (v/v in water), allowed adhesion promotion and compatibility with most common polymeric substrates. Ink phosphorescence intensity was found to vary primarily with fluorophore concentration and to a lesser extent with polystyrene particle size. The sensor performance was investigated as a function of oxygen concentrations employing two different techniques: a multi-frequency phase fluorometer and smart phone-based image acquisition. The printed sensor patch showed fast and repetitive response over 0-21% oxygen concentrations with high linearity (with R2 >0.99) in a Stern-Volmer plot, and sensitivity of I0/I21 >1.55. The optical sensor response on a surface was investigated further using two-dimensional images which were captured and analyzed under different oxygen environment. Printed sensor patch along with imaging read-out technique make an ideal platform for early detection of surface wounds associated with tissue oxygen.

A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers.

PURPOSE: Peroxisome biogenesis disorders-Zellweger spectrum disorders (PBD-ZSD) are metabolic diseases with multisystem manifestations. Individuals with PBD-ZSD exhibit impaired peroxisomal biochemical functions and have abnormal levels of peroxisomal metabolites, but the broader metabolic impact of peroxisomal dysfunction and the utility of metabolomic methods is unknown. METHODS: We studied 19 individuals with clinically and molecularly characterized PBD-ZSD. We performed both quantitative peroxisomal biochemical diagnostic studies in parallel with untargeted small molecule metabolomic profiling in plasma samples with detection of >650 named compounds. RESULTS: The cohort represented intermediate to mild PBD-ZSD subjects with peroxisomal biochemical alterations on targeted analysis. Untargeted metabolomic profiling of these samples revealed elevations in pipecolic acid and long-chain lysophosphatidylcholines, as well as an unanticipated reduction in multiple sphingomyelin species. These sphingomyelin reductions observed were consistent across the PBD-ZSD samples and were rare in a population of >1,000 clinical samples. Interestingly, the pattern or "PBD-ZSD metabolome" was more pronounced in younger subjects suggesting studies earlier in life reveal larger biochemical changes. CONCLUSION: Untargeted metabolomics is effective in detecting mild to intermediate cases of PBD-ZSD. Surprisingly, dramatic reductions in plasma sphingomyelin are a consistent feature of the PBD-ZSD metabolome. The use of metabolomics in PBD-ZSD can provide insight into novel biomarkers of disease.

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.

Cow's milk allergy in children impacts parental or caregiver calcium intake.

Food allergies have become a global epidemic, affecting more than 10% of the population and 8% of children worldwide. Eliminating or limiting a food group from the diet can adversely impact micronutrient consumption. Milk allergies can impact the amount of calcium consumed in the diet, serving as a barrier to meeting daily calcium needs. Previous research evaluates the nutritional impact food allergies may have on children diagnosed with food allergies; however, there is a marked gap in literature that investigates the impact that children's allergy may have on their parent or caregiver. We hypothesized that milk elimination in a child's diet resulting from a milk allergy is associated with inadequate calcium intake among parents. Study participants (n = 55) lived in the United States and included parents or caregivers of a child with a diagnosed milk allergy (experimental group) and parents of a child without a milk allergy (control group). Calcium intake was estimated by using the validated Calcium Assessment Tool. Results demonstrated that the experimental group consumed significantly less calcium (273 mg/d) than the control group (520 mg/d; P < .01). Notably, both groups consumed inadequate calcium relative to the calcium Recommended Dietary Allowance for adults of 1000 mg/d, although calcium supplementation was not assessed in this study. Key findings from this study indicate widespread inadequate dietary calcium intake and suggest a need for increased calcium consumption in this population.

Metabolic Syndrome and Chronic Disease Risk in South Asian Immigrants: A Review of Prevalence, Factors, and Interventions.

South Asians (SAs) are among the fastest-growing ethnic groups in the U.S. Metabolic syndrome (MetS) is a condition that is characterized by multiple health factors that increase the risk for chronic diseases, such as cardiovascular disease (CVD) and diabetes. MetS prevalence among SA immigrants ranges from 27-47% in multiple cross-sectional studies using different diagnostic criteria, which is generally higher compared to other populations in the receiving country. Both genetic and environmental factors are attributed to this increased prevalence. Limited intervention studies have shown effective management of MetS conditions within the SA population. This review reports MetS prevalence in SAs residing in non-native countries, identifies contributing factors, and discusses ways to develop effective community-based strategies for health promotion targeting MetS among SA immigrants. There is a need for more consistently evaluated longitudinal studies to facilitate the development of directed public health policy and education to address chronic diseases in the SA immigrant community.

Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review.

Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD.

Development of a Quality-of-Life Survey for Patients With Succinic Semialdehyde Dehydrogenase Deficiency, a Rare Disorder of GABA Metabolism.

Succinic semialdehyde dehydrogenase deficiency (SSADHD), a rare disorder of GABA metabolism, presents with significant neurodevelopmental morbidity. Although there is a growing interest in the concept of quality of life through patient reports as a meaningful outcome in rare disease clinical trials, little is known about the overall impact of SSADHD from the patient/family perspective. The purpose of this study was to determine issues related to quality of life and patient/family experience through a focus group discussion with family caregivers of patients with SSADHD. The discussion included the input of 5 family caregivers, and highlighted concerns related to physical function, cognitive and intellectual function, psychological and behavioral function, social function, and family impact. These themes represent appropriate starting points in the development of a quality-of-life survey that may serve as a meaningful clinical tool in future studies of SSADHD.

Simultaneous Determination of Eight Urinary Metabolites by HPLC-MS/MS for Noninvasive Assessment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health concern for which sensitive and objective diagnostic methods remain lacking. While advances in neuroimaging have improved diagnostic capabilities, the complementary use of molecular biomarkers can provide clinicians with additional insight into the nature and severity of TBI. In this study, a panel of eight metabolites involved in distinct pathophysiological processes related to concussion was quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Specifically, the newly developed method can simultaneously determine urinary concentrations of glutamic acid, homovanillic acid, 5-hydroxyindoleacetic acid, methionine sulfoxide, lactic acid, pyruvic acid, N-acetylaspartic acid, and F2α-isoprostane without intensive sample preparation or preconcentration. The method was systematically validated to assess sensitivity (method detection limits: 1-20 µg/L), accuracy (81-124% spike recoveries in urine), and reproducibility (relative standard deviation: 4-12%). The method was ultimately applied to a small cohort of urine specimens obtained from healthy college student volunteers. The method presented here provides a new technique to facilitate future work aiming to assess the clinical efficacy of these putative biomarkers for noninvasive assessment of TBI.

Zellweger spectrum disorder: A cross-sectional study of symptom prevalence using input from family caregivers.

Zellweger spectrum disorders (ZSD) are rare, debilitating genetic diseases of peroxisome biogenesis that affect multiple organ systems and present with broad clinical heterogeneity. Although many case studies have characterized the multitude of signs and symptoms associated with ZSD, there are few reports on the prevalence of symptoms to help inform the development of meaningful endpoints for future clinical trials in ZSD. In the present study, we used an online survey tool completed by family caregivers to study the occurrence, frequency and severity of symptoms in individuals diagnosed with ZSD. Responses from caregivers representing 54 living and 25 deceased individuals with ZSD were collected over an 8-month period. Both perception of disease severity and prevalence of various symptoms were greater in responses from family caregivers of deceased individuals compared to those of living individuals with ZSD. Compared with previous reports for ZSD, the combined prevalence of seizures (53%) and adrenal insufficiency (45%) were nearly twice as high. Overall, this community-engaged approach to rare disease data collection is the largest study reporting on the prevalence of symptoms in ZSD, and our findings suggest that previous reports may be underreporting the true prevalence of several symptoms in ZSD. Studies such as this used in conjunction with clinician- led reports may be useful for informing the design of future clinical trials addressing ZSD.

Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 levels.

OBJECTIVE: To examine the effect of an equivalent weight loss, by gastric bypass surgery (GBP) or by diet, on peptide YY3-36 (PYY3-36), ghrelin, and leptin levels and to determine the effect of diabetes status on PYY3-36 levels. SUMMARY BACKGROUND DATA: The increased PYY3-36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery. METHODS: Of the 30 morbidly obese women who participated in the study, 21 had type 2 diabetes mellitus, and were studied before and after equivalent weight loss of 10 kg by either GBP (n = 11) or by diet (n = 10). RESULTS: : PYY3-36 levels were higher in obese diabetic as compared with nondiabetic individuals (64.1 +/- 34.4 pg/mL vs. 39.9 +/- 21.1 pg/mL; P < 0.05). PYY3-36 levels increased markedly in response to oral glucose after GBP (peak: 72.3 +/- 20.5 pg/mL-132.7 +/- 49.7 pg/mL; P < 0.001; AUC0-180: 51.5 +/- 23.3 pg/mL x min-91.1 +/- 32.2 pg/mL x min P < 0.001), but not after diet (peak: 85.5 +/- 51.9 pg/mL-84.8 +/- 41.13 pg/mL; P = NS; AUC0-180: 68.3 +/- 38.5 pg/mL x min-61.1 +/- 42.2 pg/mL.min P = NS). Fasting ghrelin levels increased after diet (425 +/- 91 pg/mL-519 +/- 105 pg/mL; P < 0.05), but did not change after GBP (506 +/- 121 pg/mL-482 +/- 196 pg/mL; P = NS). CONCLUSIONS: Diabetes status seems to be a determinant of PYY3-36 levels. GBP, but not diet-induced weight loss, resulted in markedly increased glucose-stimulated PYY3-36 levels. The increase in stimulated PYY3-36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss. Changes in PYY3-36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss.

Do Incretins play a role in the remission of type 2 diabetes after gastric bypass surgery: What are the evidence?

Gastric bypass surgery (GBP), in addition to weight loss, results in dramatic remission of type 2 diabetes (T2DM). The mechanisms by which this remission occurs are unclear. Besides weight loss and caloric restriction, the changes in gut hormones that occur after GBP are increasingly gaining recognition as key players in glucose control. Incretins are gut peptides that stimulate insulin secretion postprandially; the levels of these hormones, particularly glucagon-like peptide-1, increase after GBP in response to nutrient stimulation. Whether these changes are causal to changes in glucose homeostasis remain to be determined. The purpose of this review is to assess the evidence on incretin changes and T2DM remission after GBP, and the possible mechanisms by which these changes occur. Our goals are to provide a thorough update on this field of research so that recommendations for future research and criteria for bariatric surgery can be evaluated.

Emotional experience in parents of children with Zellweger spectrum disorders: A qualitative study.

Zellweger spectrum disorders (ZSDs) are rare, debilitating genetic diseases of peroxisome biogenesis that require constant management and lifelong care. Nevertheless, the experience of family caregivers for children diagnosed with ZSD is not well understood. In this study, we sought to characterize the emotional experience of ZSD family caregivers. Three 90-min focus groups were conducted with thirty-seven parents (25 mothers and 12 fathers) of children with ZSD during a family advocacy conference. Focus groups were arranged by age of proband (Group 1: 0-4 years, Group 2: 5-10 years, Group 3: >11 years). Audio recordings of focus groups were transcribed and analyzed using software for coding purposes. Analyzed content was validated using peer debriefing, member checking, and method triangulation. Focus group results showed that nearly a third of ZSD caregivers described their overall emotional experience as a "rollercoaster." Additionally, three interconnected themes were identified: 1) range of emotions, 2) stressors, and 3) coping. Feeling overwhelmed and devastated were the most frequently described emotional responses. Corresponding stressors to these emotions included the burden of caregiver tasks associated with ZSD, and negative interactions with healthcare professionals. The most common coping strategies were acceptance of limitations of the diseases, redefining "normal" in the parenting experience, and advocating on behalf of the child and the patient community. This study underscores the profound emotional impact on parents who are caregivers for children with ZSDs, highlighting the utility of patient community feedback and qualitative approaches to fully characterize the overall family experience. Simple, targeted approaches focusing on improved communication between healthcare professionals and families, as well as offering resources for emotional support may greatly improve the lives of families living with ZSD and other rare pediatric diseases.

Effect of genistein on the bioavailability and intestinal cancer chemopreventive activity of (-)-epigallocatechin-3-gallate.

The green tea (Camellia sinensis) catechin, (-)-epigallocatechin-3-gallate (EGCG), has shown cancer-preventive activity in animal models. Previously, we have reported the bioavailability of EGCG in rats and mice. Here, we report that cotreatment of HT-29 human colon cancer cells with genistein (from soy) increased cytosolic EGCG by 2- to 5-fold compared with treatment with EGCG only. Inclusion of genistein, at non-cytotoxic concentrations, increased the growth inhibitory effects of EGCG against HT-29 cells (up to 2-fold at 20 microM genistein). Intragastric coadministration of EGCG (75 mg/kg) and genistein (200 mg/kg) to CF-1 mice resulted in an increase in plasma half-life (t(1/2) 148.7 +/- 16.4 versus 111.5 +/- 23.4 min) and exposure (AUC(0-->infinity) 183.9 +/- 20.2 versus 125.8 +/- 26.4 microg/ml x min) of EGCG. Cotreatment with genistein also increased the maximal concentration (C(max)), 6 h exposure (AUC(0-->360 min)), and t(1/2) of EGCG in the small intestine by 2.0-, 4.7- and 1.4-fold, respectively, compared with mice treated with EGCG only. Contrary to our expectations, the combination of 0.01% EGCG in the drinking fluid and 0.2% genistein in the diet enhanced intestinal tumorigenesis in male adenomatous polyposis coli (APC)(min/+) mice. This combination increased the multiplicity of tumors in the medial and distal small intestine: the largest increase was in tumors >2 mm in diameter (4.3-fold compared with controls). This study demonstrates that although genistein can enhance EGCG bioavailability and in vitro growth inhibitory activity, this combination enhances tumorigenesis in the APC(min/+) mouse. These results further show the need for careful cancer prevention studies in animal models and for caution when interpreting data from in vitro studies.

The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice.

In this study, we investigated the effects of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat-fed groups (r(2) = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat-fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat-fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat-fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms.

Voluntary exercise inhibits intestinal tumorigenesis in Apc(Min/+) mice and azoxymethane/dextran sulfate sodium-treated mice.

BACKGROUND: Epidemiological studies suggest that physical activity reduces the risk of colon cancer in humans. Results from animal studies, however, are inconclusive. The present study investigated the effects of voluntary exercise on intestinal tumor formation in two different animal models, Apc(Min/+) mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. METHODS: In Experiments 1 and 2, five-week old female Apc(Min/+) mice were either housed in regular cages or cages equipped with a running wheel for 6 weeks (for mice maintained on the AIN93G diet; Experiment 1) or 9 weeks (for mice on a high-fat diet; Experiment 2). In Experiment 3, male CF-1 mice at 6 weeks of age were given a dose of AOM (10 mg/kg body weight, i.p.) and, 12 days later, 1.5% DSS in drinking fluid for 1 week. The mice were then maintained on a high-fat diet and housed in regular cages or cages equipped with a running wheel for 16 weeks. RESULTS: In the Apc(Min/+) mice maintained on either the AIN93G or the high-fat diet, voluntary exercise decreased the number of small intestinal tumors. In the AOM/DSS-treated mice maintained on a high-fat diet, voluntary exercise also decreased the number of colon tumors. In Apc(Min/+) mice, voluntary exercise decreased the ratio of serum insulin like growth factor (IGF)-1 to IGF binding protein (BP)-3 levels. It also decreased prostaglandin E2 and nuclear beta-catenin levels, but increased E-cadherin levels in the tumors. CONCLUSION: These results indicate hat voluntary exercise inhibited intestinal tumorigenesis in Apc(Min/+) mice and AOM/DSS-treated mice, and the inhibitory effect is associated with decreased IGF-1/IGFBP-3 ratio, aberrant beta-catenin signaling, and arachidonic acid metabolism.

A Convergent Mixed-Methods Exploration of the Effects of Community-Engaged Coursework on Graduate Student Learning.

OBJECTIVE: To examine the impact of a community-engaged assignment on graduate student learning in the nutritional sciences. DESIGN: Convergent mixed-methods design with parallel data collection and terminal merging of data. Data were composed of grant proposals, reflection papers, and informal course evaluations from 2 semesters of the same course. Fall students wrote proposals on behalf of a community partner whereas spring students wrote fictitious grants to improve nutrition on their campus. SETTING: A large public university in northeastern US. PARTICIPANTS: Students enrolled in the fall (n = 19) or spring (n = 14) semester of the same graduate nutrition course. PHENOMENON OF INTEREST: Grant quality, student engagement, and collaboration with peers. ANALYSIS: Quantitative rubric-based rating of grant proposals, emergent and thematic qualitative coding of open-ended responses, and independent-samples t test of Likert-scale questions. Data were compared between semesters and reported in a contiguous narrative approach. RESULTS: Students across semesters experienced academic and personal gains from the assignment. Comparatively, fall students expressed enhanced engagement, improved group dynamics, more frequent application of the assignment to their lives, and a better aggregate grant score. CONCLUSIONS AND IMPLICATIONS: Both experiential and community-engaged coursework can enhance learning outcomes at the graduate level and prepare students for careers in nutrition.

Inhibition of tumorigenesis in ApcMin/+ mice by a combination of (-)-epigallocatechin-3-gallate and fish oil.

The effect of a combination of (-)-epigallocatechin-3-gallate (EGCG) with fish oil on intestinal tumorigenesis in Apc (Min/+) mice fed a high-fat diet was investigated in the present study. The combined treatment of EGCG and fish oil for 9 weeks reduced the tumor number by 53% as compared to controls while neither agent alone had a significant effect. Apoptosis was significantly increased in all treatment groups. beta-Catenin nuclear positivity in adenomas from the combination group was lower than control mice, implicating the modulation of Wnt signaling by the combination. Fish oil and the combination significantly reduced prostaglandin E 2 (PGE 2) levels in small intestinal tumors as compared to controls, suggesting modulation of aberrant arachidonic acid metabolism by fish oil. Akt phosphorylation in adenomas was significantly reduced in all treatment groups, which may have contributed to the observed increase in apoptosis. The results indicate that a combination of low doses of EGCG and fish oil can inhibit tumor multiplicity in Apc (Min/+) mice.

Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea.

The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apc(min/+) mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a dose of 0.044% in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02% to 0.32%. P.o. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear beta-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 micromol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of beta-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 micromol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apc(min/+) mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear beta-catenin and activated Akt and ERK signaling.

Wheat bran oil and its fractions inhibit human colon cancer cell growth and intestinal tumorigenesis in Apc(min/+) mice.

This study was designed to investigate the cancer preventive activities of wheat bran (WB) oil. We studied the colon cancer preventive effects of WB oil and its subfractions in the Apc(min/+) mouse model, a recognized mouse model for human colorectal cancer, and used human colon cancer cell lines (HCT-116 and HT-29) to identify possible active fractions in WB oil. Our results showed that the oil fraction of WB was more active than the water fraction against the growth of human colon cancer cell lines and that 2% WB oil significantly inhibited the overall tumorigenesis by 35.7% (p < 0.0001) in the Apc(min/+) mouse model. The WB oil was further fractioned into nonpolar lipids and phytochemicals and the phytochemical fraction was fractionated into phytosterols and phytosterol ferulates, 5-alk(en)ylresorcinols, and unidentified constituents by normal phase silica gel column chromatography. Results on cell culture showed that the phytochemical fraction had a higher inhibitory effect on HCT-116 human colon cancer cells than that of WB oil, whereas the nonpolar lipid fraction had less growth inhibitory effectiveness. However, neither fractions showed a stronger inhibition than WB oil in the Apc(min/+) mouse model. The current results demonstrate, for the first time, the intestinal cancer preventive activity of WB oil. The active ingredients, however, remain to be identified.