bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of mTOR/p70S6K in amino acid induced cardiac protection
Authors: Katayama Erika , Tsutsumi Rie , Nakaya Yutaka , Hirose Kayo , Tanaka Katsuya , Oshita Shuzo , Tsutsumi Yasuo M. 
Published: June 2021

Leucine, as an essential amino acids and activator of mammalian target of rapamycin (mTOR), promotes protein synthesis and suppresses protein catabolism. Recent studies have showed that the mTOR/p70S6K complex may mediate the beneficial effects to ischemia‐reperfusion injury. We therefore proposed that amino acids may produce cardiac protection against myocardial ischemia‐reperfusion mediated by mTOR/p70S6K.Mice were subjected to 30 min of myocardial ischemia followed by 120 min of reperfusion. Control mice were exposed to ischemia and reperfusion only. Other mice were randomly assigned to receive amino acids, administered 15 min before ischemia and/or rapamycin, a mTOR inhibitor, were given 15 min prior to amino acids preconditioned.Amino acids preconditioned mice were significantly reduced infarct size compared to control group (34 ± 4% vs. 45 ± 3% [n = 3] respectively, p<0.05) and rapamycin eliminated the protection produced by amino acids (41 ± 3% [n = 3]). Additionally, the hearts treated with amino acids had a 2‐fold increase in phosphorylation of both mTOR and p70S6K, and pretreated with rapamycin completely abolished mTOR/p70S6K phosphorylations in response to amino acids treatment.These results indicate that amino acids induced myocardial protection involves activation of the p70S6K that is mediated by the mTOR.
Phosphatidylinositol 3‐Kinase mediates the ability of retinol to inhibit colon cancer cell invasion in vitro
Authors: Griffin Jennifer N , Lane Michelle A 
Published: June 2021

Vitamin A supplementation decreases colorectal cancer metastasis and retinol inhibits phosphatidylinositol 3‐kinase (PI3K) activity. Our objective was to determine if PI3K mediates the effects of retinol on colon cancer invasion in vitro. HCT‐116 cells expressing wild‐type or constitutively active (ca) PI3K were treated with 0 (vehicle control) or 10 μM retinol for 24 hours. Matrigel‐coated Boyden chambers measured invasion. Western blot analyses determined β‐catenin, matrixmetalloproteinase (MMP)‐9 and TIMP (tissue inhibitor of MMP)‐1 levels. Zymography detected MMP‐9 activity. Our results show caPI3K blocked the ability of retinol to decrease invasion, β‐catenin and MMP‐9 protein, MMP‐9 activity, and increase TIMP‐1. Specifically, 10 μM of retinol resulted in cell invasion of 103.1 ± 6.7 and 65.9 ± 5.5, β‐catenin levels of 126.8 ± 15.1 and 63.5 ± 17.4, MMP‐9 levels of 96.2 ± 2.9 and 80.8 ± 6.2, TIMP‐1 levels of 81.7 ± 29.9 and 121.7 ± 8.9, and MMP‐9 activity of 81.5 ± 19.7 and 73.3 ± 4.7% vehicle control ± SEM for the caPI3K and wild‐type PI3K cell lines, respectively. Thus, PI3K mediates the ability of retinol to decrease colon cancer invasion. Sponsor: NIH grant #5 R21 CA120414‐02.Grant Funding Source: NIH grant #5 R21 CA120414‐02
Justicidin A inhibits AKT/mTOR and activates type III PI3K/beclin 1 signaling pathways leading to autophagy of human colorectal cancer cells
Authors: Su Chun‐Li , Yen Cheng‐Hsin , Lin Chun‐Nan , Won Shen‐Jeu 
Published: June 2021

Justicidin A (JA), a pure compound isolated from Justicia procumbens, is a traditional herbal remedy for treatment of fever, pain, and cancer in Taiwan. Treatment of JA not only increased the expression of autophagic marker microtubule‐associated protein 1 light chain‐II by immunoblotting and confocal microscopy, but also augmented the formation of acidic vesicular organelles by flow cytometry in HT‐29 cells. Further study indicated that the expression of p‐AKT, p‐mTOR, p‐p70S6k was decreased whereas that of type III PI3K, becline 1, and Atg5‐Arg12 was increased in JA‐treated cells. Annexin V‐FITC and propidium iodine staining followed by flow cytometry revealed that induction of early apoptosis was displayed at 12 h that was later than the induction of autophagy. Of note, pre‐treatment of the cells with autophagy inhibitor 3‐methyladenine reduced JA‐induced early apoptotic rate. Oral administration of JA (6.2 mg/kg) once a day for 56 consecutive days was shown to suppress the growth and induce apoptosis and autophagy of HT‐29 cells transplanted to NOD‐SCID mice, suggesting chemotherapeutic potential of JA on human colorectal cancer cells.(Supported in part by National Science Council, Taipei, Taiwan, No. NSC 96‐2313‐B‐309‐001‐MY2 and NSC 98‐2313‐B‐003‐002‐MY3).
Oral amino acids and testosterone therapy to improve muscle mass and quality of life during chemotherapy in recurrent cervical cancer: A case study
Authors: Dillon Edgar Lichar , Randolph Kathleen M , Casperson Shanon L , Durham William J , Urban Randall J , Levine Lyuba , Diaz‐Arrastia Concepcion , Sheffield‐Moore Melinda 
Published: June 2021

Muscle wasting is by far the most important phenotypic feature of cancer cachexia, though little success has been achieved toward reversing or preventing this catabolic process. Anabolic interventions including testosterone and amino acid supplements may be beneficial in reducing and/or reversing muscle wasting in these patient populations.A 48‐year‐old recurrent cervical cancer patient was scheduled to receive three 21‐day cycles of cisplatin and topotecan chemotherapy. She consented to a 10 week blinded interventional pilot study were she received daily amino acid supplements and weekly injections of testosterone enanthate before and during the weeks of chemotherapy treatment. Blood, Dual Energy X‐ray Absorptiometry (DEXA) scans, and Functional Assessment of Cancer Therapy ‐ General (FACT‐G) questionnaire data were collected before and after the 10 week period.Total serum testosterone concentrations, total and trunk lean body mass, and body weight increased after 10 weeks. Total and trunk fat mass decreased. FACT‐G scores improved.Concomitant treatment of oral amino acids and testosterone may be a viable therapeutic option for fighting cachexia and improving quality of life during chemotherapeutic treatment of recurrent cervical cancer. A double‐blinded, placebo‐controlled interventional study is in progress (NCT00878995).Funding through NIH/NCI RO1 CA127971 and T32 CA117834.
Association between Serum Cytokine Concentrations, Flavonol Intake and Colorectal Adenoma Recurrence in the Polyp Prevention Trial (PPT)
Authors: Bobe Gerd , Murphy Gwen , Albert Paul S. , Sansbury Leah B. , Schatzkin Arthur , Lanza Elaine , Colburn Nancy H. , Cross Amanda J. 
Published: June 2021

BackgroundSerum cytokine concentrations are considered to be markers of inflammation and may be used to identify individuals at increased risk or in early stages of colorectal carcinogenesis. There are certain dietary components that may have anti‐inflammatory properties, including flavonols, which are found in fruits and vegetables.AimsTo determine whether serum concentrations of IL‐1β, IL‐2, IL‐8, IL‐10, IL‐12p70, GMCSF, IFNγ, and TNFα, measured over time, are associated with flavonol intake and colorectal adenoma recurrence.MethodsWe estimated odds ratios (ORs) and 95% confidence intervals (CIs) for cytokine concentrations, flavonol intake, and adenoma recurrence in 872 participants from the intervention arm of the PPT.ResultsFlavonol intake was inversely related with IFNγ concentrations. A decrease in IL‐2 concentrations during the trial was associated with any adenoma recurrence (4th versus 1st quartile, OR = 1.68, 95% CI: 1.13–2.49) and advanced adenoma recurrence was inversely related with a decrease in IL‐1β (OR = 0.37, 95% CI: 0.15–0.94) and IL‐10 (OR = 0.39, 95% CI: 0.15–0.98). Individuals with above median flavonol intake plus equal or below median cytokine concentrations had the lowest risk of advanced adenoma recurrence.ConclusionHigh flavonol intake combined with a decrease in or low cytokine concentrations may be most protective against advanced adenoma recurrence.
Protein supplementation during 6 mo weight loss enhances body composition changes in older women
Authors: Mojtahedi Mina C , Thorpe Matthew P , Richey Abby L , Johnson Curtis L , Karampinos Dimitrios C , Georgiadis John G , Layman Donald K , Evans Ellen M 
Published: June 2021

Adverse increases in adiposity and reductions in fat free mass (FFM) are age related changes in body composition and are linked to declines in physical function in older women. Higher protein intake in weight loss may augment fat mass (FM) loss and attenuate FFM loss, which may benefit function. This study assessed effects of 6 mo weight loss supplemented with powdered protein or placebo on body composition and function in older obese women. Women (63.8±3.4 yrs, BMI 32.9±4.1 kg/m2) were prescribed an energy‐restricted diet (1500 kcal/d; 15, 65, 30% of energy from protein, CHO and fat, respectively) and randomly assigned to 2 × 25g/d of whey protein (PRO, n=8) or maltodextrin (CARB, n=7) supplementation. Measures included whole body FM and FFM with DXA; thigh muscle, subcutaneous (SUBQ), intermuscular and intramyocellular fat with MRI; knee extension and flexion strength with isokinetic dynamometry. PRO trended towards greater weight loss (−10.6±6.7%, −5.0±4.0%; p=0.078), had greater reductions in FM (−18.9±10.6%, −8.0±4.2%; p=0.024) than CARB, but no significant difference in FFM (−4.0±4.9%, −2.0±4.1%; p=0.414). %SUBQ thigh fat change (−6.1±3.0%, −1.3±1.7%; p=0.003) was the only significant MRI outcome. Groups did not differ in leg strength changes. Higher protein intake in weight loss in older women enhances FM reductions while preserving FFM; however, these changes do not impact changes in physical function.Grant Funding Source: National Dairy Council, Carraway Foundation
Adipocity‐associated plasma biomarkers in breast cancer patients and their relationship with dietary nutrient intake and BMI
Authors: Yeon Jee‐young , Kim Jeong‐seon , Sung Mi‐Kyung 
Published: June 2021

Body weight gain among breast cancer(BC) survivors, is a known risk factor for disease recurrence. The objective of this study was to investigate the relationship between nutrient intake, body mass index(BMI) and adipocity related biomarkers in BC patients. The histologically confirmed BC patients included 312 women (167 premenopausal, 123 postmenopausal). The average age and BMI were 47.84 y and 23.46 kg/m2. Study results indicated that the subjects consume the highest quartile of fat or the third quartile of retinol had the highest plasma 8‐isoprostane level. Correlation coefficient analysis indicated that the BMI of study subjects was positively associated with plasma level of interleukin(IL)‐6(p<0.001), IL‐8(p<0.05), monocyte chemotactic protein(MCP)‐1(p<0.001) and leptin(p<0.001). Plasma adiponectin level was negatively associated with BMI (p<0.001). Among biochemical markers, adiponectin was negatively associated with the plasma level of IL‐6(p<0.05) and leptin(p<0.001). Plasma leptin level was positively associated with 8‐isoprostane(p<0.001) and MCP‐1(p<0.001). Our results suggest that BMI is closely related to plasma adipocity‐related markers and a proper management of body weight may reduce the risk of BC recurrence by suppressing the level of adipocity‐related molecules. This study was funded by Korean Science and Engineering Foundation (R01‐2007‐000‐11293‐0)Grant Funding Source: Nutrition(ASN)
Peroxisome proliferator‐activated receptor‐gamma ligand suppressed leptin‐mediated expression of interleukin‐8 and tumor angiogenesis in human colon cancer cells
Authors: Wang Fu‐Yu , Tang Feng‐Yao 
Published: June 2021

Colorectal cancer is one of the leading causes of cancer death in western countries. Previous studies have demonstrated that overexpression of leptin is strongly associated with risk of human colon cancer. However, the effect of leptin on tumor angiogenesis during the development of human colon cancer has not been demonstrated well yet. The present study would investigate the role of peroxisome proliferators activated receptors (PPAR)‐gamma ligand in leptin–mediated expression of interleukin‐8 (IL‐8) and tumor angiogenesis in human colon cancer cells. Our results showed that leptin dose‐dependently (0, 0.0625, 0.25, 1 μM) induced the expression of IL‐8 in human colon cancer HT‐29 cells. Conditioned medium from leptin‐stimulated human colon cancer HT‐29 cells would also induce tubular formation in human umbilical vein endothelial cells (HUVEC). Treatment of Troglitazone (0.1 and 5μM), a specific PPAR‐ γ agonist, would suppress leptin‐mediated expression of IL‐8 in human colon cancer HT‐29 cells up to 9% and 38%, respectively. Furthermore, troglitazone–treated conditioned medium from cancer cells would suppress tubular formation in HUVEC. Take together; our results suggest that PPAR‐γ ligand could act as an important chemo‐preventive agent to suppress leptin‐mediated IL‐8 expression and tumor angiogenesis in human colon cancer.Grant Funding Source: National Science Council grant under agreement No. 97‐2320‐B‐039‐043‐MY3,
Metabolic syndrome in healthy, multiethnic adolescents in Toronto: the use of fasting blood glucose as a simple indicator
Authors: Vuksan Vladimir , Rogovik Alexander , Peeva Valentina , Beljan‐Zdravkovic Uljana , Stavro Mark , Jenkins Alexandra , Dias Andre , Devanesen Sudi , Fairgrieve Christopher , Hanna Amir 
Published: June 2021

ObjectivesTo assess the presence of metabolic syndrome (MetS) features in healthy, normal‐weight, multiethnic adolescents and to determine whether fasting blood glucose (FBG) may be a simple indicator of its presence.MethodsA cross‐sectional study using a convenience sample of secondary school students. GLM ANCOVA adjusted for multiple pairwise comparisons by the post hoc Tukey‐Kramer test was used to assess differences among the tertiles of FBG.ResultsA total of 182 adolescents from 62 Greater Toronto Area (GTA) secondary schools were recruited (44% Caucasian, 34% South Asian, and 22% Chinese), with mean(SD age 17.4±0.9 years, BMI 22.1±3.4 kg/m2, and FBG 4.92±0.4 mmol/L. Analysis with GLM ANCOVA across the tertiles of FBG (3.83–4.78 mmol/L, 4.79–5.08 mmol/L, and 5.09–6.45 mmol/L) showed significant linear increases of BMI (p<0.005), waist circumference (p<0.001), systolic blood pressure (p<0.001), and diastolic blood pressure (p<0.05) with increasing FBG. Stepwise multiple regression analysis indicated systolic blood pressure and waist circumference as independent predictors of the increased FBG level.ConclusionsMetS markers are present in a sample of healthy multiethnic adolescents in GTA. FBG could be used as a simple indicator of MetS to allow for early detection of MetS presence and introduction of preventive lifestyle measures.
Branched Chain Fatty Acids are taken up and metabolized by Cultured Human Intestinal Cells (Caco‐2)
Authors: Ran‐Ressler Rinat Rivka , Kothapalli Kumar Sesha Durga , Glahn Raymond P , Brenna James Thomas 
Published: June 2021

BackgroundWe recently showed differences in the distribution of branched chain fatty acids (BCFA) in the vernix and meconium of healthy newborns: BCFA with < 16 carbons were detected in vernix but not in meconium. In this study we tested if: 1. BCFA are taken up and metabolized by the enterocyte, and 2. BCFA affect gene expression involved in fatty acid (FA) metabolism, using a Caco‐2 cell culture model.MethodUptake study: Caco‐2 cells were grown on 6 well plates for 14 days. Cells were incubated with graded levels of 4 BCFA or control for 4 hours. Cells were harvested for lipid classes and FA analysis.Gene expression studyCaco‐2 cells were grown in flasks and incubated for 24 hours with a mixture of 5 BCFA or control at 7 and 14 days post seeding. RNA was reverse‐transcribed into cDNA which was subjected to semi‐quantitative PCR.ResultsBCFA were taken up by Caco‐2 cells and differentially incorporated into cellular lipid fractions. Small amounts of elongation products were detected. The expression of ELOVL3 (very long chain fatty acid elongase) and BCAT (Branched‐chain amino transferase) was higher at BCFA‐ treated cells at 7 days compared to 14 days post seeding.ConclusionCaco‐2 cells take up BCFA. Their differential incorporation into lipid classes indicates selective metabolism. Expression of BCFA‐related genes is under developmental control when cells are BCFA‐treated.Support: NIH grant T32HD007331
The dose response effects of lean beef on LDL‐C change: Results from the BOLD (Beef in an Optimal Lean Diet) Study
Authors: Roussell Michael Antonion , Gaugler Trent , West Sheila , Vanden Heuvel John , Kris‐Etherton Penny 
Published: June 2021

Observational data demonstrate an association between increased red meat intake and incidence of cardiovascular disease (CVD). However, several clinical trials that compared cholesterol lowering diets containing lean beef vs. chicken or fish have not observed differences in the lipid‐lowering response. We hypothesized that when saturated fat levels (SFA) are maintained within the recommended range (<7% of calories), increased quantities of lean beef will not increase LDL‐C.The BOLD study employed a cross‐over controlled feeding study design to evaluate the effects of lean beef intake on established and emerging CVD risk factors. Thirty‐seven men and women (LDL‐C <110mg/dL) were fed an Average American control diet (AAD; 11.3% SFA, 1oz beef/d), DASH (6.5% SFA, 1.8oz beef/d), BOLD (6.4% SFA, 4.5oz beef/d), and BOLD+ (6.1% SFA, 6.3oz beef/d) diets for five weeks with a 2 week washout period between diet. LDL‐C significantly decreased on average by 17.9mg/dL for the 3 test diets compared to the AAD control diet. A multivariate regression analysis was used to examine the effect of a dose‐dependent change in lean beef intake (oz/d) on LDL‐C change. There was no significant effect of increasing lean beef intake on LDL‐C change (p=0.4896) in diets that provided < 7% of calories from SFA.In conclusion, increasing intake of lean beef in the context of a heart healthy diet does not attenuate the LDL‐C lowering effect. Supported by: National Cattlemen's Beef Association.
Effects of consuming a yogurt containing plant sterols, as part of a Therapeutic Lifestyle Changes (TLC) Diet, on blood lipids in men and women with primary hypercholesterolemia
Authors: Jonnalagadda Satya S , Maki Kevin C. , Reeves Mathew S. , Rains Tia M. , Witchger MarySue 
Published: June 2021

Objective was to assess the effects of an intervention involving TLC diet, including consumption of a plant sterol containing yogurt, on the fasting lipoprotein lipid profile and blood pressure in men and women with primary hypercholesterolemia. Study included men and women (n = 34), 40–69 yrs, with fasting LDL‐C of 130–210 mg/dL. At week 0, participants were instructed on the TLC diet and provided with yogurt to be consumed twice daily (0.6 g plant sterol/serving) for six weeks. Fasting lipids were measured at baseline (weeks ‐1 and 0) and weeks 2, 4, and 6. Participants were mostly female (73.5%) and of non‐Hispanic white ethnicity (91.2%) with a mean age of 52.7 yrs and BMI of 26.8. Significant reductions from baseline were observed for LDL‐C (−8.2 %; p < 0.001), TC (−6.9 %; p < 0.001), non‐ HDL‐C (−7.3 %; p < 0.001) and HDL‐C (−4.5 %; p = 0.023). Blood pressure decreased from 121.5/76.9 mm Hg at baseline to 116.1/74.6 mm Hg at the end of treatment (p < 0.03 for systolic and diastolic). The mean MEDFICTS score decreased from week 0 (53.7) to week 6 (32.4; p < 0.001), indicating compliance with the TLC diet. These results show that the TLC diet including consumption of yogurt containing plant sterols (1.2 g/day) was associated with improvements in total, LDL, and non‐HDL‐C and blood pressure in men and women with primary hypercholesterolemia.Funding: General Mills Bell Institute of Health and Nutrition, Minneapolis, MN.
Docosahexanoic acid intake from food and supplement sources of pregnant women living in a non‐coastal community
Authors: Campbell Christina Gayer , Filipowicz Rebecca 
Published: June 2021

Maternal docosahexanoic acid (DHA) consumption for fetal development has become increasingly recognized. Limited data exists regarding the intake of the omega‐3 fatty acid DHA in pregnant women living in non‐coastal communities. The purpose of this analysis was to quantify total daily DHA intake from food and supplements in pregnant women living in a non‐coastal community.Sixty‐three women completed a 107‐item food frequency questionnaire between 28–35 weeks of gestation. Intake data was analyzed with Nutritionist Pro. Prenatal recommendations of 200 mg DHA/d were used as a reference. Descriptive statistics were calculated with Excel.Overall the median intake of DHA from food and supplement sources was 199 mg/d (mean ± SD; 219 ± 240 mg/d; 9–1645 mg/d). Approximately one‐third (23 of 63) of the participants reported consuming a DHA supplement. For supplement users, median intake was 321 mg/d (376 ± 300 mg/d) however the median DHA intake for the non‐supplement users was 75 mg/d (125 ± 120 mg/d). Of the 63 women, only 12 were able to meet the recommended daily intake of 200 mg/d from food alone.More than half of the women in our study living in a non‐coastal community were unable to meet current recommendations of 200 mg/d from food alone. Regardless of the dietary source more education is needed to promote prenatal DHA consumption.Grant Number P20 RR‐16455‐07 from the NCRR, a component of the NIH.
The feasibility of replacement feeding as an HIV prevention method in Lilongwe, Malawi: Results of the BAN Study
Authors: Parker Megan E , Bentley Margaret E , Adair Linda , Jamieson Denise , Ellingston Sascha , Chasela Charles , Mkhomawanthu Chimwemwe , Tembo Martin , Martinson Francis , van der Horst Charles 
Published: June 2021

International guidelines recommend exclusive breastfeeding (EBF) to 6 months among HIV‐infected mothers choosing to breastfeed, with cessation of BF once replacement feeding is acceptable, feasible, affordable, sustainable and safe. When mothers wean, they are challenged to provide an adequate replacement diet. This study investigates use and acceptability of a peanut‐based ready‐to‐use, micronutrient‐enriched paste (RUF) as a breastmilk substitute when provided to 6–12 mo. old infants of HIV+ mothers, as part of the BAN (Breastfeeding, Antiretroviral, and Nutrition) Study. A sub‐sample of mothers (n=45) was interviewed when their child was 15–16 mo. old. Quantitative and qualitative analyses explored issues related to weaning strategies using RUF from 6 to12 mo. and challenges faced when RUF was no longer provided at 12 mo. Mothers reported 8 strategies used for cessation of BF at 6–7 months including gradual reduction of BF episodes, expressing breastmilk into a cup, and using alternate caregivers. RUF was well accepted by mothers and infants (98%) and incorporated into the traditional infant diet. When RUF was no longer provided, infants stopped accepting the staple maize porridge, particularly among food insecure households. Early BF cessation is a feasible HIV prevention method among this low‐income population in Malawi when supported by the provision of RUF as a breast milk substitute.Grant Funding Source: CDC and the National Institutes of Health, National Institute of Child Health and Human Development (NICHD, 1R03HD057775‐01)