bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Multiple Inositol Polyphosphate Phosphatase as Apoptosis Biomarker
Authors: Hossain Md Zakir , Kleve Maurice G.
Published: June 2021

The multiple inositol polyphosphate phosphatase (MINPP) which regulates cellular levels of inositol phosphates, is located on chromosome 10q23 in human cells and is a member of histidine phosphatases family. In this study, we have determined the antigenicity of MINPP. We proposed different possible peptides and designed the experimental methodology to produce MINPP polyclonal antibodies. To further elucidate the physiological role of MINPP we have characterized the human MINPP antibodies using direct western immunoblotting of bacteria (E. coli), yeast (Saccharomyces cerevisae) expressing MINPP. SDS‐PAGE identified 58 KDa protein band using mammalian pancreatic cancer cell lysates (Panc1) and homogenate from rat liver and microsomal fraction of rat liver and kidney after immunoprecipitations with MINPP antibodies. The MINPP enzyme activity was determined by two methods. First, inositol phosphates separation by column chromatography using the microsomal fraction of rat liver and kidney, total cell lysates from rat liver in a scintillation counter using tritiated‐inositol (3H‐inositol). Second, a customized colorimetric method was developed without any radio‐active 3H ‐inositol using 96 wells plate reader. Using different apoptosis inducers, we have seen that MINPP expression increased in programmed cell death in a dose dependent manner. Supported by University of Arkansas at Little Rock.
Risperidone attenuates apoptotic cell death in 293A‐TREK‐2 cells
Authors: Kang Kee Ryeon , Lee Ji‐Young , Kang Dawon
Published: June 2021

Two‐pore potassium channel protein TREK‐2 was known to be inhibited its activity by antipsychotic chlorpromazine. However, the underlying mechanisms between TREK‐2 and psychiatric disorders such as schizophrenia are still unclear. It is well known that antipsychotics have anti‐apoptotic effects in various cell types. In order to understand the role of TREK‐2 involved in pathophysiology of schizophrenia, over‐expressed rat TREK‐2 in 293A cells (293A‐rTREK‐2) were treated with risperidone, atypical antipsychotics, and observed its protective effects against apoptotic cell death. We found that the expression of TREK‐2 could elicit the activation of ERK activities, and induce PARP cleavage in 293A‐rTREK‐2 cells up to 48 h after risperidone treatment. Furthermore, we also observed that the effect of risperidone in 293A‐rTREK‐2 cells is correlated with the increased sub‐G1 phase of cell cycle by FACS analysis. Thus, it is demonstrated that TREK‐2 expression could induce apoptotic cell death by abolishing anti‐apoptotic effects of risperidone through ERK pathway. KOSEF grant for MRC (R13‐2005‐012‐01003‐0) and grant for the NRF of Korea (2009‐0072300) are supported for this work.
Loss of DNA Repair Protein and Cell Death in Helicobacter pylori‐Infected Gastric Epithelial Cells
Authors: Kim Hyeyoung , Chu Sang Hui , Lim Joo Weon
Published: June 2021

Cell death linked to DNA damage has been implicated in Helicobacter pylori (H. pylori) ‐ infected gastric diseases. During DNA damage, DNA repair proteins, Ku70 and Ku80, prevent cell death but severe DNA damage beyond the capacity of the DNA repair proteins triggers cell death. It has been hypothesized that the decrease in Ku70 and Ku80 may be related to cell death in H. pylori‐infected gastric epithelial cells. In this study, it was found that H. pylori induced cell death with increasing time and amounts of H. pylori added to the cells, which was determined by decreased in viable cell numbers and poly(ADP‐ribose) polymerase (PARP) cleavage. H. pylori resulted in significant decrease in both cytoplasmic and nuclear Ku protein levels as well as nuclear Ku DNA end‐binding with time and amounts of H. pylori added to the cells. H. pylori‐induced decrease in Ku proteins in cytoplasm and nucleus was in parallel with increase in ubiquitinated Ku70 and Ku80 in the whole cell extracts. H. pylori‐induced alterations in Ku expression, cell death and DNA fragmentation were inhibited by a calpain inhibitor, calpeptin and a proteasome inhibitor, lactacystin. In conclusion, loss of Ku proteins may cause the loss of defense against DNA damage and thus, underlie the mechanism of cell death in gastric epithelial cells after H. pylori infection.
TIAF1 is an essential partner for tumor suppressors p53‐ and WWOX‐mediated apoptosis
Authors: Chang Nan‐Shan , Lee Ming‐Hui , Lin Sing‐Ru
Published: June 2021

Tumor suppressors p53 and WOX1 (also named WWOX or FOR) participate in TGF‐β signaling, whereas the regulatory control is largely unknown. TIAF1 is a TGF‐β1‐induced factor, which regulates p53 activation, TNF cytotoxicity, and TGF‐β/Smad signaling. By multi‐cancer tissue microarray analyses, here we determined that TIAF1 levels are significantly upregulated in many cancer tissues such as in colon, lung, prostate, brain and skin (~0.5–1.5 fold increases). Knockdown of TIAF1 by small interfering RNA (siRNA) resulted in cellular resistance to apoptosis caused by TNF, UV light, staurosporine, daunorubicin, and etoposide. Without TIAF1, apoptosis caused by overexpressed p53 and WOX1 was blocked. As determined by co‐immunoprecipitation and FRET, TGF‐β1 and apoptosis stimuli rapidly increased the complex formation of p53, WOX1 and TIAF1 in 1 hr, followed by slow dissociation. Ectopic WOX1, in the presence or absence of wild type p53, excessively induced SMAD‐responsive element or promoter activation, which led to apoptosis. TIAF1 significantly inhibited the promoter activation. Together, TIAF1 controls apoptosis caused by p53 and WOX1 via the TGF‐β/Smad signaling. (Supported by National Science Council and National Health Research Institute, Taiwan, and Department of Defense, USA)
Analysis of a simulated in vivo environment for selective induction of apoptosis
Authors: Dover Cheri Denise
Published: June 2021

Apoptosis is thought to play a major role in biological processes and in establishing effective treatments for cancer. The objective of this study was to examine the response of human erythroleukemia (HEL) cells when exposed to known apoptosis inducers and to analyze a simulated in vivo environment to determine whether normal cells (WI‐38 cells) and HEL cells were affected by the chemicals.

The HEL cells were treated with camptothecin (CP), vehicle alone, and various heteroarotinoids (HETS) twenty‐four hr after subculture and incubated for an additional 48–72 hr. The cells were harvested and monitored for apoptosis, growth, and viability. Apoptosis was quantitated using the Hoechst/propidium iodide assay. Preliminary results proved one of the five HETS tested had significant elevated levels of apoptosis when compared to the vehicle alone.

In an attempt to mimic an in vivo environment, HEL cells, grown in suspension, were introduced to a normal human adherent cell population at various cell densities and allowed to incubate for 72 hr. The majority of the HEL cells adhered to the WI‐38 cells. A large population of HEL cells was resistant to removal from the WI‐38 cells following a vigorous shake, suggesting a strong bond between the cells. In order to determine the selectivity of apoptosis, CP was added to the system. The initial results suggest that both cell types were negatively affected by CP. Support was provided by SRU.
Identification of novel protein interactors for the circadian regulatory protein Period 2 using bacterial two‐hybrid screening
Authors: Hamann Jens , Kim Kevin , Bevan David R , Finkielstein Carla V
Published: June 2021

Period 2 (Per2) is a core circadian protein that affects multiple biological functions including hormone release and metabolic rate. Disruptions in the expression of Per2 can result in abnormalities in these functions. In this study, we perform a bacterial two‐hybrid screening assay using the C‐terminal region of human Per2 to find novel interactors that could modulate its circadian activity. Three hundred and twenty clones from a human liver cDNA library were identified, purified and validated by clustering using DAVID (database for annotation, visualization, and integrated discovery) suite of programs. This analysis allows the rapid visualization of interactors that are closely related to each other in function. We found many clusters with enrichment scores above 1.5, a relative value above which a cluster is considered significant. A large group was found to be involved in the immune response, yielding an enrichment score of 3.29. A score of 2.38 for a group involved in apoptosis further solidifies the fact that hPer2 has been shown to play a major role in apoptosis of tumor cells. These results show that the circadian protein Period 2 crosstalks among different signaling pathways conferring a pleiotropic role to its function. Studies are underway to identify the biochemical properties of various interactions and their physiological relevance in normal cells and for disease development.
Regulation and Role of Heme Oxygenase‐1 (HO‐1) During Inflammation in Human Gingival Fibroblasts (HGF)
Authors: Madani Sheedeh , Evans Michel , Chambers Mariah , Gorski Grzegorz , Madani Mansoor , Borghaei Ruth
Published: June 2021

Periodontitis is the most common cause of adult tooth loss in the U.S., with an estimated 1 in 3 adults suffering from some form and 10–15% of adults developing severe forms. In addition to its direct impact, periodontitis also contributes to the development of several other diseases, including cardiovascular disease, pre‐term low birth weight, and diabetes. Although the primary function of HO‐1 is the breakdown of heme to carbon monoxide, iron and bilirubin, it has also been shown to play an important role in wound repair and the resolution of inflammation by mechanisms involving homeostatic regulation of the redox state of cells. A series of experiments has been designed to determine whether and to what extent the levels of HO‐1 mRNA and protein are regulated by inflammatory cytokines in HGF isolated from individuals with or without periodontitis. Preliminary results show that HO‐1 mRNA is expressed in HGF cultures derived from patients with periodontitis and that mRNA levels are inhibited over 60% by Interleukin‐1 at 6 hours (10 ng/ml, p < 0.001). Interestingly however, HO‐1 protein levels as measured by ELISA are not decreased by IL‐1. Experiments are currently underway to address this apparent paradox, as well as the potential role of HO‐1 in regulation of inflammatory mediators in HGF.
Relationship between serum and synovial fluid concentration of leptin and degree of osteoarthritis
Authors: Schmidt Jenna , Hooshmand Shirin , Arjmandi Bahram
Published: June 2021

Currently 27 million Americans are affected by osteoarthritis (OA) however, its etiology remains unclear and effective therapies to prevent or halt OA are not available. Evidence suggests that loss of body fat is more important to decrease risk of OA than general weight loss emphasizing the role of fat tissue and its secretions and suggesting a metabolic link between obesity and OA.

The objective of this project was to explore the relationship between serum and synovial fluid concentrations of leptin and the degree of OA. Blood and synovial fluid samples were obtained by an orthopedic surgeon from a total of 40 men and women with knee OA undergoing arthroscopic or total knee replacement surgery. Synovial fluid and serum samples were analyzed in duplicate using ELISA method to determine the concentration of leptin.

Our findings show a distinct correlation between BMI and serum leptin levels in both males and females (R=0.505, p=0.02; R=0.569, p=0.008). We found that in both men and women, the degree of OA was associated with serum leptin concentrations (R=0.487, p=0.02; R=0.498, p=0.04). Our data also show that females have higher levels of leptin in both serum and synovial fluid than males. Although our results are promising in terms of relation among leptin levels in synovial fluid and serum and the degree of OA, further studies are needed to investigate the exact role of leptin in increasing the severity of OA.
Dietary medical advice and health behavior of minorities with diabetes
Authors: Vaccaro Joan A , Huffman Fatma G
Published: June 2021

Objective

to examine the relationships among reported dietary, medical advice given and its association with health behavior of Mexican Americans (MA) and Black non‐Hispanic (BNH) as compared to White non‐Hispanic (WNH) adults diagnosed with diabetes.

Method

Secondary analysis of data acquired through the National Health and Nutrition Survey (NHANES) for the years 2007–2008. Variables for medical advice, diet and anthropometric measures were merged by subject ID number. First day 24‐hour recall was used for dietary data. Sample weights were applied.

Results

Controlling for obesity, MA [OR=2.28 (1.06, 4.93)] and BNH [OR=2.79 (1.43, 5.46)] were more likely than WNH to report that they were told to increase their physical activity (p=0.022). MA [OR=2.15 (1.03, 4.46)] and BNH [OR =1.83 (1.16, 2.88)] were more likely to report being told to reduce fat or calories than WNH (p=0.009). Being told to reduce fat or calories was not a predictor of percent calories from total or saturated fat.

Conclusions

There were significant differences in reported medical advice received for diabetes care by race/ethnicities. These findings suggest ethnic variations in patient‐provider communication and may be a consequence of their health beliefs.
Changes with Age: Increases in BMI found with healthier diets and lifestyles
Authors: Dooley Kerin K , Yu Kyeong Hee , Hong Mee Young
Published: June 2021

Many preventable chronic diseases are related to diet and health behaviors. The purpose of this study was to examine the differences in health behaviors and dietary intakes at different stages of life to observe where shifts in behavior take place. Health, lifestyle behaviors, and dietary intake were assessed via questionnaire to 596 Southern Californians. Participants were divided into three groups based on age and stage of life: teenagers, college, and adults. Findings showed significant differences in intakes among the groups, with trends towards healthier food intake with age. Adults consumed less meat, more fish, less fast food, and had a decline in snacking (P<0.05). Adults and college aged were more likely to make food choices based on food labels (P<0.01) and follow United States Department of Agriculture (USDA) dietary guidelines (P <0.05). However, an increase in body mass index (BMI) was observed in adults, with the average BMI in the overweight category, as well as a shift in body image that found adults were more likely to consider themselves overweight, while teens and college aged were more likely to consider themselves thin or fit. In addition, declines in exercise (P<0.01) and exercise strength (P<0.01) were found between teens and adults. This study found that although adults practiced healthier food and lifestyle behaviors, BMI and body image shifted towards becoming overweight and exercise declined.
Influence of the built and social environment on adolescent eating behaviors in Baltimore City: Findings from the Baltimore Healthy Eating Zones study
Authors: Christiansen Karina , Qureshi Farah , Schaible Alex , Coutinho Anastasia , Dennisuk Lauren , Rowan Megan T , Park Sohyun , Surkan Pamela , Gittelsohn Joel
Published: June 2021

Low‐income minority youth in Baltimore City live in an obesogenic food environment with limited access to healthy foods. The Baltimore Healthy Eating Zones Project (BHEZ) seeks to improve access to and consumption of healthy foods in low‐income neighborhoods surrounding Baltimore City recreation centers. Qualitative research, informed by an ecological perspective, was conducted to identify environmental factors impacting eating behaviors of target youth. Two focus groups and 20 in‐depth interviews were conducted with 21 Baltimore City adolescents aged 10–16. Six themes that emerged included those relating to the built environment (accessibility of food, neighborhood safety, school food) and the social environment (family health history, role modeling, peer behaviors). The influence of the family and adult role models emerged as the most salient reported influence on youth eating habits. These findings were used to inform the BHEZ intervention, specifically in developing more targeted messaging. Our findings and resulting intervention strategies have the potential to effectively promote healthy eating and reduce obesity risks among low‐income minority youth and their adult caregivers in Baltimore City.

Grant Funding Source: The Robert Wood Johnson Foundation
The effects of the “En Balance” diabetes education program on physical activity and diabetes control
Authors: Wheeler Gina , Beeson Larry , Montgomery Susanne , Bhajri Khalid , Schulz Eloy , Firek Anthony , DeLeon Marino , Cordero‐MacIntyre Zaida
Published: June 2021

Objective

To assess the effect of ‘En Balance’ on blood sugar control and physical activity.

Methods

Hispanic subjects (n=16 males, 23 females) participated in a 3 month education intervention with baseline and three month assessments of physical activity using the Arizona Activity Frequency Questionnaire. Paired sample t‐tests were used to assess mean changes in physical activity energy expenditure, blood samples, anthropometric measures, and body composition using fan beam dual X‐ray absorptiometry (DXA); Hologic Discovery A (software v. 12.6).

Results

After 3 months, there was a significant increase in moderate intensity physical activity energy expenditure (μ=368±894 kcal/day, p<.01) and high intensity physical activity energy expenditure (μ=405±2569 kcal/day, p=.05) compared to baseline, and significant reductions in hemoglobin A1c (−0.90%, p=.01), total cholesterol (−13.44 mg/dl, p=.01), LDL cholesterol (−10.28 mg/dl, p=.03) and waist circumference (−1.52 cm, p=.04).

Conclusion

Culturally sensitive diabetes education led to significant improvements in moderate and high intensity physical activity energy expenditure and glucose control in this population of Hispanics with diabetes.

Funded by: NIH award 5P20MD001632
Demographic and socioeconomic correlates of body fat assessed using DXA in US children and adolescents
Authors: Nguyen Tuan Thanh , Butte Nancy F , Wang Youfa
Published: June 2021

Few studies examined the association between accurately measured body fat (BF) and socio‐demographic characteristics using nationally representative data in the US. We studied BF distribution and its association with socio‐demographic characteristics, including age, sex, race/ethnicity and poverty income ratio (PIR) in 8–19‐y‐old US youth in NHANES 1999–2004 (n = 7479). BF (measured by DXA) was used in continuous (%BF and fat mass index (FMI = fat mass/height2 (kg/m2)) and categorical (normal, overfat, and excess fat; using %BF cut points 25%, 30% for boys and 30%, 35% for girls) scales. The sex‐race‐specific prevalence of overfat+excess fat was: in boys, 45%, 33% and 57%; and in girls, 63%, 58% and 72%, in whites, blacks and Mexican Americans, respectively. Low‐income youth had higher %BF, FMI, overfat+excess fat rate. The distribution of %BF and FMI varied substantially by age, sex and ethnicity. After controlling for these factors, (1) one unit increase in PIR (scales 0 to 5‐high income) associated with a decrease by ~0.2 kg/m2 FMI, 0.5% (absolute) BF, and 14% (relative) in excess fat rate (P < 0.001); (2) compared with participants with PIR ≥4, those with PIR < 3 had an increase of ~1 kg/m2 FMI, 2% BF (absolute), and 70% (relative) in excess fat rate (P < 0.001; P trend < 0.05). Higher prevalence of excess body fat among US children from low‐income families calls for targeted strategies to fight pediatric obesity.

Main source of research support: NIH/NIDDK (R01DK81335‐01A1), NIH/NICHD (1R01HD064685‐01A1, 1R03HD058077‐01A1, R03HD058077‐01A1S1), Vietnam Educational Foundation (VEF), and Thrasher Research Fund.
Oxidative potential of dietary oils used and consumed by residents of Prairie View, Texas
Authors: Doore Lorna , Skeene Dawnette , McKinney Darvel , McWhinney Velva
Published: June 2021

A change in the quality of dietary oils which are available for use and consumption by residents of Prairie View, Texas was examined. The change in dietary oil quality was determined by measuring the peroxide value, conjugated dienes levels and fatty acid profile of unheated oils and oils heated at 180°C for 12 hours over a two‐day period. There were 183 varieties of dietary oils and fats taking into account cooking oils, salad oils and shortenings categorized into 28 oil type, i.e. coconut, canola, avocado. Olive oils and its varieties accounted for approximately 43% of the oils that were available. Of the four chosen oil types, vegetable oils had the highest overall peroxide value (12.83 mEq O2/mg of oil) whereas blended oil had the lowest peroxide value (6.23 mEq O2/mg of oil). Wesson brand of oils had the highest peroxide value (14.00 mEqO2/mg of oil) and Parade had the lowest peroxide value (6.70 mEq O2/mg of oil). The peroxide values of Vegetable, Corn and Canola were different from Blended oils. Heating dietary cooking oils over time will increase the peroxide levels in the oil. The information provided by this study is useful in the education of consumers to facilitate informed choices.
Effects of diet‐induced obesity on secondary tumor development and plasma cytokine expression in mice
Authors: Yan Lin , DeMars Lana
Published: June 2021

We studied the effects of diet‐induced obesity on secondary tumor development and growth in mice. Three‐wk old male C57BL/6 mice were fed the AIN‐93G or a 45% fat diet (n=25) for 7 wks before they were subcutaneously injected with 2.5×105Lewis lung carcinoma cells. The primary tumor was resected 2 wks later, and mice were maintained on their respective diets for an additional 2 wks. There was a 2‐fold increase in the number of lung metastases in the high‐fat diet‐fed mice compared to the AIN‐93G‐fed mice (P<0.05). Feeding tumor‐bearing mice the high‐fat diet resulted in ≥50% increases in expression of 16 plasma cytokines (including leptin, IL‐1β, MCP‐1, TIMP‐1 and VEGF), and an approximately 50% decrease in adiponectin, compared to the AIN‐93G‐fed tumor‐bearing mice. Results of ELISA assays showed that were no differences in plasma concentrations of IL‐1β, MCP‐1, TIMP‐1 and VEGF in non‐tumor‐bearing mice fed the AIN‐93G or the high‐fat diet, but significant increases in these cytokines in tumor‐bearing mice fed the AIN‐93G diet compared to the non‐tumor‐bearing mice fed the same diet, and further significant increases in these cytokines were observed in tumor‐bearing mice fed the 45% fat diet. The present study demonstrated that diet‐induced obesity enhanced secondary tumor development and growth in tumor‐bearing mice and that this aggressiveness was accompanied with increases in angiogenic cytokines in plasma.
Enhancement of phase 2 enzyme activities with sodium butyrate is associated with the nuclear translocation of Nrf2 and p53
Authors: Matsui‐Yuasa Isao , Enami Yuka , Yaku Keisuke , Kurajyo Chika , Kojima‐Yuasa Akiko
Published: June 2021

Introduction

Dietary fiber fermentation by the colonic bacterial flora produces short chain fatty acids, acetate, propionate and butyrate. Among them, butyrate is considered to be the major energy substrate for colonocytes and, at least in rats, seems to protect against colonic carcinogenesis. In this study, we examined the effect and the mechanisms of short chain fatty acids on the activity of phase 2 enzymes.

Results

Sodium butyrate increased phase 2 enzymes, GST and NQO in a dose‐dependent manner, however, other short chain fatty acids did not increase these activities. The mechanism of the induction of phase 2 enzymes with sodium butyrate was related to the increase in the Nrf2 and Nrf2/c‐jun complex protein levels in the nucleus. These results suggested that the Nrf2/c‐jun nuclear translocation levels were more important to the induction of phase 2 enzymes than the Nrf2 levels themselves. Furthermore, sodium butyrate, but not other short chain fatty acids, caused the decrease in the levels of nuclear fraction p53 in a dose‐dependent manner.

Conclusion

These results suggested that sodium butyrate brings about the increase in the activities of phase 2 enzymes via an increase in the Nrf2 and Nrf2/c‐jun complex protein levels in the nucleus and a decrease in the levels of nuclear fraction p53.
Bioavailability of anti‐carcinogenic hydroxylated polymethoxyflavones in mice
Authors: QIU PEIJU , Song Mingyue , Guan Huashi , Guo Shanshan , Zheng Jinkai , Charoensinphon Noppawat , Nutakul Wasamon , Ngauv Pearline , Xiao Hang
Published: June 2021

Previously we have showed that hydroxylated polymethoxyflavones (OH‐PMFs), such as 5‐hydroxy‐6,7,8,3′,4′‐pentamethoxyflavone (5HPMF) and 5‐hydroxy‐6,7,8,4′‐tetramethoxyflavone (5HTMF) are potent anti‐cancer dietary compounds in cell culture. Bioavailability is one of the key factors that can dictate the in vivo efficacy of dietary bioactive compounds. Herein, we studied the bioavailability of 5HPMF and 5HTMF in CF‐1 mice. We developed a highly sensitive HPLC method for the detection of OH‐PMFs in biological samples. The method was fully validated in terms of linearity, accuracy and precision. The limit of detection (LOD) in serum was determined as being 0.71 and 1.97 ng/mL (ppb) for 5HPMF and 5HTMF, respectively, demonstrating an over 150‐fold increase in sensitivity in comparison with previously published method. At 60 min after oral gavage (100 mg/kg), 5HPMF, mostly in free form, reached its peak level of 5.3 μM, while 5HTMF showed similar trend but with the peak level 8.28‐fold lower than that of 5HPMF. In urine, both 5HPMF and 5HTMF existed mainly as sulfate‐ and glucuronic acid‐conjugates, and urine level of total 5HPMF was 9.06‐fold higher than that of 5HTMF. These results demonstrated that 5HTMF had much lower bioavailability, which may due to its poor solubility in GI tract.
Higher plasma homocysteine is associated with increased risk of colorectal polyps
Authors: Huang Yi‐Chia , Lin Chun‐Che , Chen Fang‐Pei , Chen Tan‐Hsia
Published: June 2021

Colorectal adenomas are considered as precursors of colorectal cancer. B‐vitamins (i.e., folate, vitamin B‐6 and B‐12) involve in the homocysteine metabolism and play as coenzymes in one‐carbon metabolism, which may have a critical role in the colorectal polyps progression. The purpose of this study was to examine the effects of B‐vitamins and homocysteine on the risk of colorectal polyps. This study was an observational case‐control design. Forty‐seven subjects with colorectal polyps [29 adenomatous polyps (AP), 18 hyperplastic polyps (HP)] and 95 age‐, sex‐matched healthy subjects were recruited. Subjects with AP and HP had significantly higher plasma homocysteine levels than did healthy subjects. There was no significant difference in serum folate and vitamin B‐12 and plasma pyridoxal 5′‐phosphate among the three groups. B‐vitamins had no significant effect on the risk of colorectal polyps. However, subjects with higher plasma homocysteine (OR, 2.18; 95% CI, 1.23 – 3.88) level exhibited significantly increased risk of colorectal polyps after body mass index, diastolic blood pressure, total cholesterol and B‐vitamins were additionally adjusted. Plasma homocysteine, but not B‐vitamins, is a strong predictor of the risk of colorectal polyps while subjects had adequate B‐vitamins status. This study was supported by National Science Council (NSC 97‐2320‐B‐040‐031‐MY3), Taiwan.
White button, shiitake, and portabella mushrooms inhibit the secretion of vascular endothelial growth factor (VEGF) and the proliferation of the androgen dependent LNCap prostate cancer cell line
Authors: Kuvibidila Solo , French Christine
Published: June 2021

VEGF, a potent angiogenic factor secreted by various normal and cancer cells, has been implicated in cancer growth and metastasis. Plasma and urinary levels of VEGF usually correlate with cancer severity implying that its reduction by bioactive compounds in foods may modulate tumor growth. The antitumor properties of exotic mushrooms have long been known and have been attributed to immunomodulatory, cytotoxic, and cytostatic properties. However, their effect on VEGF is unknown. The goal of this study was to determine whether mushroom extracts inhibit cancer cell proliferation via reduction of VEGF secretion. LNCap prostate cancer cells, 1.25 × 105 were incubated with 0–100 μg/ml of ethanol extracts of white button mushrooms (WBM), portabella (PM), and shiitake (SM) for 3, 6, and 24 h in 10% FCS‐supplemented medium. VGEF secreted in the culture medium was assayed by ELISA. Mushrooms extracts had no effect on VEGF secretion after 3 h of incubation, but decreased the levels in a dose dependent fashion after 6 and 24 h (i.e. 100 μg/ml & 24 h: WBM, 19%, PM 46%; SM 43%, p<0.05, n=4 assays). Cell viability and proliferation assessed by MTT test decreased by 5–37%. Reduction of VEGF was not due to a defect in IL‐6 and IL‐8, inducers of VEGF, since neither cytokine was detectable in the same cultures. Although the mechanism has yet to be investigated, our data suggest that edible mushrooms may reduce the risk of metastatis by inhibiting VEGF. Source of support OCAST, Startup funds from Oklahoma State University.
Enhanced effectiveness of using herbs versus their isolated bioactive compounds in a model of castrate‐resistant prostate cancer
Authors: Zhao Yi , Huang E‐Chu , Whelan Jay
Published: June 2021

Prostate cancer (PCa) is the second most common type of cancer among males in the USA. Bioactive phytonutrients have been shown to have anticancer properties in vitro when isolated from their plant sources; however, their relative effective concentrations are orders of magnitude greater than achievable in humans. As such, is it possible to achieve an effective human equivalent dose by using the herb these compounds were originally derived from or with combinations of herbs or their bioactives? In this study, we investigated the differential effects of the bioactive compounds berberine, baicalin and curcumin and compared their effectiveness to goldthread, skullcap and turmeric, respectively, when used in isolation or in combinations. Proliferation of CWR22Rv1 cells (castrate‐resistant PCa cell line) were tested with each bioactive as compared to their corresponding herbs (and in combination) using the Chou‐Talalay method to assess synergy. In each case, sensitivity for growth inhibition was enhanced with the herb (or when used in combination) versus the single compound. Increased expression of the cell cycle inhibitor p21 and inhibition of bcl‐2 accompanied these results. The results show that herbs and their combination can inhibit cell proliferation at lower doses compared to isolated bioactive compounds by inhibiting cell proliferation and enhancing apoptosis. Supported, in part, by the TN AES.
The anti‐tumor activity of Antrodia camphorate in melanoma cells: Modulation of Wnt/β‐catenin signaling
Authors: Tsou Hsiao‐Tung , Yang Hsin‐Ling , Hseu You‐Cheng
Published: June 2021

Antrodia camphorata is well known in Taiwan as a nutritional food. The objective of our study was to determine if fermented culture broth of Antrodia camphorata (AC‐10; 40–120 μg/mL) could modulate the key elements of Wnt pathway in murine melanoma cell (B16F10); an efficacy for chemoprevention of this malignancy. The suppression of β‐catenin, a key mediator of Wnt signaling pathway, was seen in B16F10 cell with AC‐10 administration. The transcriptional targets of c‐myc and cyclin D1 were also dramatically downregulated. We also observed that AC‐10 caused the G1 arrest that was mediated through reductions in the levels of cyclinD1 and CDK4, and increases in p27 and p21 levels in B16F10 cell. In addition, treatment B16F10 with AC‐10 resulted in a significant dose‐dependent increase in apoptosis, which was associated with DNA fragmentation, sub‐G1 phase accumulation. Gelatin zymography and western blotting showed that reduced cell invasion with AC‐10 treatment correlated with MMP‐9 and MMP‐2 expression. These results suggested that AC‐10 may exert anti‐tumor activity by modulating Wnt/β‐catenin pathway.

The source of research support: American Society for Nutrition (ASN)
Differential effects of broccoli‐derived phytochemicals indole‐3‐carbinol and its dimer 3, 3’‐diindolylmethane on liver X receptor‐responsive genes in human prostate cancer cells
Authors: Wang Thomas , Milner John , Kim Young S
Published: June 2021

This study examined the effects of indole‐3‐carbinol (I3C) and 3, 3’‐diindolylmethane (DIM) on liver X receptor (LXR)‐dependent pathways. DIM, but not I3C, induced transcription of ABCG1 and ABCA1 mRNA, two LXR‐responsive ATP‐binding cassette transporters involved in cholesterol efflux, in the androgen responsive LNCaP cells, but not the androgen non‐responsive PC3 cells. Exposure of LNCaP cells to 5 microM DIM for 48 hrs led to a 5‐fold increase in ABCG1 and ABCA1 mRNA levels. Knockdown of LXR alpha and beta isoforms using siRNA abrogated the ability of DIM to induce ABCG1 but not ABCA1 mRNA. Furthermore, knockdown of androgen receptor (AR) expression in LNCaP cells with AR siRNA blocked DIM induction of ABCA1 and ABCG1 mRNAs. The results suggest that DIM modulates cholesterol metabolism through both androgen‐mediated and LXR‐dependent pathways in prostate cancer cells. Furthermore, these effects are unique to DIM but not I3C suggesting that these two dietary components exert cancer preventive effects through different mechanisms.
Tart cherry‐enriched diets reduce atherosclerosis and mortality in mice
Authors: Seymour E Mitchell , Kondoleon Michael G , Huang Michael G , Kirakosyan Ara , Kaufman Peter B , Bolling Steven F
Published: June 2021

Epidemiologic data suggest that anthocyanin intake is inversely related to cardiac mortality. In animals, intake of anthocyanin‐rich tart cherries reduces cardiovascular risk factors, but the specific effect upon atherosclerosis is unknown. Male ApoE‐null mice were provided diet containing 21% total fat. A cohort of ApoE‐null mice were provided 1% of the diet as tart cherry powder from pitted, individually quick frozen tart cherries. Diets were matched for calorie and carbohydrate content. Mice were sacrificed after five months of feeding. Cherry intake reduced serum oxidative stress marker malonyldialdehyde(−17%), inflammation marker C‐reactive protein(−36%), and total cholesterol(−26%). Cherry intake also reduced early mortality(−65%) and reduced lipid deposition in the aortic arch(−29%) and abdominal aorta(−8%). Several inflammation‐related mRNAs and proteins were altered in aortas of cherry‐fed mice including tumor necrosis factor‐α and monocyte chemotactic protein‐1. However, mRNA related to lipid uptake and storage were unchanged. The data suggest that cherry intake may have reduced atherosclerosis by reduced serum cholesterol and/or reduced local inflammation in the aortic wall, but not by altered cholesterol uptake, itself. In conclusion, anthocyanin‐rich tart cherry intake reduced atherosclerosis, biomarkers of cardiovascular risk, and atherosclerosis‐related mortality.
The effects of whole or skinned peanut intake on body composition, lipid profile and fibrinogen in obese women on a low‐energy dietary intervention
Authors: Costa Neuza Maria Brunoro , Fialho Cristiane Goncalves Oliveira , Bressan Josefina , Alfenas Rita Cassia Goncalves , Mattes Richard D
Published: June 2021

Despite their high energy density, peanut consumption has little effect on body weight. It is also associated with reduced risk of cardiovascular disease. Whether they should be recommend for inclusion in energy‐restricted diets is not established. This study evaluated the blood lipid profile, fibrinogen and body composition of obese women on an energy‐restricted diet. Twenty‐four women, 20–50 years old were assigned to 3 groups and consumed 56g of: whole peanut (WP), skinned peanut (SP), and no peanut (NP). No significant group differences were observed for body weight, BMI, lean and fat mass, BMR, waist circumference over the 8 week intervention. Although reported energy intake was lower on NP than WP or SP, weight loss was 1.7, 3.2, and 0.5 kg in the groups, respectively. Total blood cholesterol was significantly (P<0.05) reduced in both groups consuming peanuts (16%), but not on NP. LDL (−15.1% and −21.8%) and fibrinogen (−18.3% and −4.3%) were also reduced in the peanut groups (WP and SP, respectively), but not significantly. The consumption of peanut with or without skin within the context of a low‐energy dietary intervention led to a lipid profile associated with lower CVD risk without a rise of body weight.

Sponsored by Peanut Institute and CNPq
Effect of age on postprandial lipemia after a high‐fat meal high and low in cereal fiber
Authors: angadi siddhartha s , weltman nathan , rodriguez jessica , patrie james , brock david , weltman arthur , gaesser glenn
Published: June 2021

To assess the effect of age on postprandial lipemia, 10 youths (ages 10–17), 12 adults (ages 19–63), and 13 seniors (ages 65–75) completed two randomly assigned meal challenges on separate days, following an overnight fast: a high‐fat (HF) meal (550 kcal; 35.0 g fat; 34.6 g protein; 24.7 g carbohydrate; 0.3 g fiber), and a HF + fiber meal that included 45 g ready‐to‐eat cereal (680 kcal; 36.3 g fat; 41.3 g protein; 61.7 g carbohydrate; 16.3 g fiber). HF resulted in similar and significant (p<0.05) 4‐hr postprandial increases in triglycerides (TG; mg/dl) across all groups (youths: 105.2 ± 30.9 to 188.1 ± 61.9; adults: 105.1 ± 53.2 to 199.7 ± 90.7; older adults: 94.8 ± 35.7 to 196.8 ± 64.5). Fiber attenuated the TG increase in youth by ~50% (100.2 ± 75.3 to 140.3 ± 57.9; p = 0.056) but not in adults (138.1 ± 97.7 to 212.9 ± 136.6) or older adults (105.5 ± 45.6 to 183.4 ± 65). We conclude that age did not affect postprandial increases in TG following ingestion of a high‐fat meal. However, adding high‐fiber (largely insoluble) ready‐to‐eat cereal to a HF meal attenuated the postprandial hyperlipidemia in youth. This may be due in part to the fact that the cereal fiber content of the meals was not adjusted in proportion to body mass. Because postprandial lipemia may increase cardiovascular disease risk, our findings may have important clinical application in meal planning for children and adolescents.

Funding: NIH RR MO100847, Wheat Foods Council
Antioxidant and Immuno‐stimulating Activity of Sesquiterpene Compounds Isolated from Artemisia iwayomogi in HepG2 and RAW 264.7 Cells
Authors: Jang Hae‐Dong , Lee Sang‐Hyun , Kim Jin‐Kyoung , Ra Jeong‐Chan , Kim Young‐Ho
Published: June 2021

Artemisia iwayomogi has been used as a medical herb to prevent liver diseases such as jaundice, acute hepatitis and cirrhosis in Asian countries. In this study, we investigated the antioxidant and anti‐inflammatory activity of sesquiterpene compounds isolated from Artemisia iwayomogi by in vitro and cellular models. The antioxidant activity was estimated using in vitro ORAC and AAPH‐ or Cu2+‐induced HepG2 cell model. The antioxidant activity of sesquiterpene compounds dose‐dependently increased between 1 and 10 uM in ORAC assay system. In AAPH‐ or Cu2+‐induced HepG2 cells, 10 uM of sesquiterpene compounds efficiently reduced oxidative stress when compared to control. The immune‐stimulating activity of sesquiterpene compounds was estimated using DAF‐FM fluorescence probe and western blotting. The increased formation of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) by sesquiterpene compounds treatment may contribute to immune‐stimulating activity of RAW 264.7 cells. These results indicate that sesquiterpene compounds isolated from Artemisia iwayomogi have the potential as a pharmaceutical food to prevent oxidative stress‐related chronic diseases.

Grant Funding Source: ASN
Quantification of an inverse linear relationship between carbohydrate consumption and HDL levels in healthy individuals and individuals with the metabolic syndrome
Authors: Checchio Tina Marie , Sweeney Kevin , Volek Jeff , Fernandez Maria Luz
Published: June 2021

The objective of this study was to describe the relationship between carbohydrate (CHO) intake and plasma HDL cholesterol concentrations. A population model was constructed using pooled individual level data across 11 dietary intervention trials with a total of 378 subjects. Nine of these studies involved weight loss interventions where macronutrient composition was modified, mainly CHO intake. The duration of the intervention ranged from 4 to 12 wks. Approximately 33% of the subjects were classified with metabolic syndrome at baseline. Preliminary results suggest an inverse relationship between CHO intake and HDL in both healthy subjects and those characterized with the metabolic syndrome. The most significant source of differences between subjects was HDL cholesterol at baseline. If baseline HDL information is not accounted for, then sex, metabolic syndrome status, and triglycerides were important predictors of HDL concentrations with regard to CHO consumption. Although the inverse relationship was maintained regardless of metabolic syndrome classification, preliminary data suggest that those subjects with metabolic syndrome respond differently to CHO restriction than healthy individuals. In the presence of metabolic syndrome, a more aggressive CHO restriction may be needed to achieve comparable increases in HDL levels as those observed in healthy individuals.
Compartmental model of perfusion studies of intestinal uptake of B‐6 vitamers in rats
Authors: Coburn Stephen , Townsend Douglas
Published: June 2021

We have been working toward developing a compartmental model of vitamin B‐6 metabolism which can respond appropriately to a variety of circumstances. In this project we used data from three intestinal perfusion reports (Mehansho et al., J.Nutr., 109:1542, 1979; Hamm et al., J.Nutr. 109:1552, 1979; Buss et al., J.Nutr. 110:1655, 1980) and SAAM II (Univ. of Washington, Seattle, WA) to develop a 25 compartment model describing the movement of vitamers from the lumen to the mucosa and into the perfusate. The model includes binding kinetics in the mucosa to generate steady state conditions over extended time. Although it is frequently assumed that pyridoxic acid(PA) is produced from pyridoxal, PA concentrations were mostly closely correlated with pyridoxal phosphate (PLP). Therefore, the model includes fluxes between PLP and PA. The model also includes erythrocyte compartments to account for increased uptake when erythrocytes were present in the perfusate or in whole animal experiments. The final model describes the intestinal uptake of pyridoxine, pyridoxal, pyridoxal phosphate, pyridoxamine and pyridoxamine phosphate over a wide range of concentrations and in response to phosphate inhibition.
Estimates of the duration of untreated acute malnutrition in children from Niger
Authors: Isanaka Sheila , Grais Rebecca F. , Briend André , Checchi Francesco
Published: June 2021

Expected incidence is the most appropriate measure to project the needs of a nutritional treatment program over time in terms of staffing, food and other treatments, but the direct estimation of incidence is rarely feasible at the onset of an intervention. While incidence may be approximated as prevalence/average duration, ethical constraints preclude measurement of the duration of acute malnutrition in the absence of treatment. We used a compartmental model to estimate the duration of untreated moderate (MAM) and severe acute malnutrition (SAM) in children aged 6–60 months. The model is informed by data from a community‐based cohort of children in Niger followed from August 2006 to March 2007. Maximum likelihood estimates for the duration of untreated MAM, defined by weight‐for‐height Z score and mid‐upper arm circumference, were 75–81 days and 101–116 days, respectively. The duration of untreated SAM, defined by weight‐for‐height Z score, was 45 days. The duration of untreated MAM appears to be shorter among children aged 6–35 months compared to those aged 36–60 months. Such estimates of the duration, and thus incidence, of untreated malnutrition can be used to improve projections of program needs and estimates of the global burden of acute malnutrition. This work was supported by the Department of Nutrition for Health and Development, World Health Organization (SI) and by Médecins Sans Frontières (RFG).
Parameter identifiability and Extended Multiple Studies Analyses (EMSA) of a compartmental model for vitamin A (VA) kinetics: fixing fractional transfer coefficients [L(I,J)s] for absorption
Authors: Park Hyunjin , Tang Guangwen , Green Michael H.
Published: June 2021

In VA compartmental models in humans, variability in absorption of the oral dose impacts numerical identifiability. Using previous data on serum VA kinetics in 11 U.S subjects given [2H8]retinyl acetate (Tang et al., Am J Clin Nutr, 2003) and a related 6‐compartment whole‐body model (Cifelli et al., J Nutr, 2008), we investigated whether fixing two of the absorption parameters would improve identifiability. Based on mean values in past models, we fixed L(2,1) = 50, where L(2,1) represents initial processing of the ingested dose and L(5,2) = 0.5, where L(5,2) represents direct secretion of retinol bound to retinol‐binding protein from enterocytes into plasma. For each subject, data were fit to the model using the Windows version of the Simulation, Analysis and Modeling software and then a population model was generated using EMSA. Statistical certainty was evaluated from the model sum of squares for each subject; numerical identifiability of estimates was evaluated based on fractional standard deviations (FSD) and correlation coefficients (r) after EMSA. All parameters had FSDs that were < 0.5 and none of the parameters had an r above 0.8. We conclude that the relationship L(5,2) = 0.01[L(2,1)] is associated with a model fit that has adequate statistical certainty and that fixing two L(I,J)s related to absorption improves parameter identifiability and reduces the number of adjustable parameters to just five.

Grant Funding Source: USDA‐58‐1950‐7‐707
Preschool Children's Ability to Identify Fruits and Vegetables in Different Physical States
Authors: Cox Tiffany Brooke , Petrocci Elena Marie , Carraway‐Stage Virginia , Goodell L. Suzanne
Published: June 2021

The information that children are taught about fruits and vegetables (FV) at the preschool age (3–5 years of age) can ultimately shape their health‐related decisions for the rest of their lives. The purpose of this study is to test preschool children's ability to identify FV in both their whole (i.e. Whole apple) and transformed (i.e. Applesauce) form. A pictorially‐based survey was developed to assess preschooler's knowledge of 20 commonly consumed FV in a variety of states. Children were shown large photographs of each FV and asked to verbally identify the food. Considering the current stage of cognitive development among this population, it was hypothesized that preschool children would be challenged in differentiating between FV in their whole and transformed forms. This study will ultimately provide baseline information for the development of a hands‐on curriculum focused on educating and exposing preschool children to FV.