bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition behaviors of congregate and home delivered meal participants: the short term impact of nutrition education and counseling
Authors: Wunderlich Shahla M , Bai Yeon , Piemonte Jacqueline
Published: June 2021

The purpose of this study is to investigate nutrition behaviors and risk factors (RF) of seniors participating in government sponsored nutrition programs, Congregate Meal Program (CGM) and Home Delivered Meal Program (HDM), in Hudson County New Jersey. A two‐year intervention study (2007–2008) was conducted with 476 participants (n=354 CGM, n=122 HDM, 74.6% completion rate). Participants received regular topical nutrition education/counseling during intervention. The impact of the intervention was evaluated using ANOVA/chi‐square on Nutrition Survey Risk Screening (pre‐ vs. post‐). Demography of participants was white (55.5%), women (66.7%), and widowed (45.5%) and 75.5 years ± 10.5. The proportion of participants having ≥ 2 medical conditions was greater in 2008 (p<0.01). After intervention, nutrition RF scores improved: 5.76 to 5.32 (p=0.14) in CGM, 8.1 to 6.1 (p<0.01) in HDM. A slight improvement in nutrition behaviors was noted: eating ≥ 2 meals/day in HDM (76 to 81.6 %, p= .310), eating ≥ 5 servings of fruits/vegetables in CGM (38 to 41.4 %, p=.398), and alcohol drinking ≥ 3 servings in CGM (8.4 to 4.8%, p=0.08). Participation in these programs helps seniors to stay healthy and improve overall wellness. There is a need for consistent nutrition assessment and evaluation of the participants to determine long‐term effects as the older population is rising. Supported by DHHS, Hudson County Area Agency on Aging.
Physical Activity Intervention for Osteoporosis Prevention in Black Older Adults
Authors: Babatunde Oyinlola T , Campa Adriana , Himburg Susan P , Newman Frederick L , Dixon Zisca
Published: June 2021

Background

Physical activity (PA) is one of the lifestyle behaviors considered important in osteoporosis prevention. This study examined the effect of the Revised Health Belief Model theory‐based education program on osteoporosis prevention. The PA component is reported here.

Research method

A repeated measure, randomized, wait‐list control design with 6‐weekly education sessions was offered to 130 consented black older adults in community settings in South Florida. The two groups were evaluated on the effect of the program on changes in calcium intake and PA after the program. PA benefits/barriers were discussed and demonstrated along with nutrition topics. PA was measured using Physical Activity, Osteoporosis Self‐Efficacy and other questionnaires based on the constructs of the theory.

Results

A total of 110 (experimental 59, wait‐list 51) completed all assessments. Mean age was 70.15±10.44 yrs and 90.0% were female. Reported PA scores were not significantly different (p>.05, η2 =.02), however osteoporosis self‐efficacy scores indicated participants perceived they could change their behaviors to impact their health (p<.05, η2=.20).

Conclusion

Though a combined dietary and PA program was effective with an Asian group, this population has more resistance to change PA behavior. Further studies are needed to explore alternative strategies to improve PA in this minority group.

Grant Funding Source: N/A
Maternal B‐vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis among offspring in the Apc+/1638N mouse
Authors: Ciappio Eric D , Liu Zhenhua , Mason Joel B , Brooks Ryan S , Bronson Roderick T , Crott Jimmy W
Published: June 2021

Folate and other B‐vitamins play important roles in DNA methylation, and adequate intakes of these nutrients have been implicated in the prevention of colon cancer. Concentrations of B‐vitamins in the maternal diet may impact disease susceptibility in offspring. Therefore, we investigated the effect of maternal B‐vitamin intake on intestinal tumorigenesis in offspring. Three groups of 6‐week old female C57BL/6 mice were fed diets either deficient, replete, or supplemented with folate, vitamin B2, B6, and B12 for 4 weeks, then mated with male Apc+/1638N mice. Females remained on their respective diets throughout mating, pregnancy and the suckling period (11 weeks total). After weaning, all Apc+/1638N pups were fed a replete diet (AIN‐93), regardless of maternal diet. At 32 weeks of age, 58% and 63% of pups born to deficient and replete mothers, respectively, exhibited tumors in the small intestine compared to 21% of pups born to supplemented mothers (p<0.025). Furthermore, a higher percentage of tumors collected from pups of deficient mothers displayed invasive behavior compared to tumors from pups of replete mothers (p=0.03). These data indicate that maternal B‐vitamin supplementation suppresses tumorigenesis in Apc+/1638N offspring relative to deficient and replete maternal diets and furthermore that maternal B‐vitamin depletion accelerates the acquisition of invasive characteristics in tumors.

Grant Funding Source: USDA CRIS # 1950‐5100‐074‐01S
Resveratrol attenuates hepatocellular carcinogenesis without affecting cardiac function
Authors: Meszaros J. Gary , Luther Daniel J. , Ohanyan Vahagn , Shamhart Patricia E. , Bishayee Anupam
Published: June 2021

Hepatocellular carcinoma (HCC) causes more than one million deaths worldwide yearly. Clinical and epidemiological data indicate that chemoprevention may be the best strategy to combat HCC, however the majority of available cancer chemopreventative drugs have proven to be mildly to severely cardiotoxic. Resveratrol (RES), the naturally occurring antioxidant and anti‐inflammatory agent in grapes and red wine, inhibits carcinogenesis via several mechanisms. Recently, we reported that dietary RES significantly prevents chemically‐induced liver tumorigenesis in rats. One of the mechanisms of RES‐mediated chemoprevention of hepatocarcinogenesis could be related to its anti‐inflammatory action through hepatic cyclooxygenase‐2 inhibition. The present study was to evaluate the cardiac effects of RES during experimental hepatocarcinogenesis. The cardiotoxicity of RES was assessed by monitoring cardiac function using echocardiography. Dietary administration of RES for 18 weeks dose‐dependently suppressed chemically‐induced hepatic tumor multiplicity. RES did not cause any deficits in cardiac function, but rather this agent improved fractional shortening and cardiac index. Our results suggest that RES‐mediated chemoprevention of rat liver carcinogenesis does not induce adverse effects on cardiac function, suggesting that resveratrol may be a viable chemopreventative compound for human HCC.
Medicinal herbs inhibit prostate cancer (PCa) via PI3 kinase and p21 mechanisms
Authors: Huang E‐Chu , Chen Guoxun , Baek Seung J , McEntee Michael F , Whelan Jay
Published: June 2021

Our preliminary data showed that a combination of medicinal herbs is far superior in inhibiting PCa growth compared to individual herbs. We explored the molecular mechanisms responsible for these effects in vitro (22Rv1 PCa cells) and in vivo (using a CWR22 PCa cell xenograph model). Zyflamend®, a mixture containing extracts of 10 medicinal herbs, inhibited growth of 22Rv1 cells (individual herbs had no effect) by inhibiting PI3 kinase activity and downstream signaling, i.e, reductions in pAKT, SREBP‐1c, FAS, androgen receptor (AR), IGF‐1R and induction of p21and p27. Cell cycle inhibitor p21 is commonly lower in PCa, and Zyflamend® dramatically increased and stabilized p21 mRNA and protein through a p53‐independent mechanism. The p21 effects were confirmed with SiRNA experiments. Reductions in cell proliferation coincided with these molecular effects along with increases in apoptosis. This herbal combination (but not individual herbs) suppressed expression of Class I and II histone deacetylases (HDACs), suggesting epigenetic regulation of p21. In vivo, Zyflamend® enhanced tumor regression following androgen withdrawal by inhibiting HDACs, IGF‐1R, and AR expression, all critical in preventing PCa relapse. Our results suggest this herbal combination coordinately affects multiple signaling pathways to inhibit PCa tumor cell growth and promote cell death. (Supported by NewChapter, Brattleboro, VT).

Grant Funding Source: NewChaper Inc.
Inhibition of Lung Cancer Cell Growth by Polymethoxyflavones from Sweet Orange
Authors: Charoensinphon Noppawat , Qiu Peiju , Dong Ping , Ngauv Pearline , Xiao Hang
Published: June 2021

We isolated 6 closely related polymethoxyflavones (PMFs) from sweet orange, and studied their effects on the growth of two human non‐small cell lung cancer cells. The permethoxylated PMFs, namely nobiletin, 3,5,6,7,8,3′,4′‐heptamethoxyflavone (HMF), and tangeretin, showed dose dependant growth inhibition on H1299 and H460 cells. Interestingly, three monohydroxylated PMFs, namely 5‐hydroxyl nobiletin (5HN), 5‐hydroxyl HMF (5HH), and 5‐hydroxyl tangeretin (5HT), that are derived from the three permethoxylated PMFs correspondingly showed much stronger inhibitory effects on the same lung cancer cells than their counterparts. In H460 cells, IC50 of 5HN, 5HH, and 5HT were 6.3, 17.8, and 44.0‐fold lower than those of their permethoxylated counterparts, respectively. Cell cycle analysis revealed that all 6 PMFs caused cell cycle arrest at G0/G1 phase, while 5HH and 5HT also increased G2/M cell population. The Annexin V/PI co‐staining assay revealed that PMFs had different effects on cell death. While other PMFs showed marginal effects on the apoptosis, 5HH and 5HT significantly increased percentage of lung cancer cells undergoing early and late apoptosis by 4 to 6 fold in comparison with the control cells. Our results demonstrated that hydroxylation in the PMF structures enhanced their growth inhibitory effects on human lung cancer cells by potentiating their activities on cell cycle arrest and pro‐apoptosis.

Grant Funding Source: University of Massachusetts Amherst
Effects of dietary Se deficiency on the metabolic phenotype and glucose metabolism‐related gene expression of the diet‐restricted GPX1 overexpressing mice
Authors: Pepper Matthew P. , Vatamaniuk Marko , Yan Xi , Roneker Carol A. , Lei Xin Gen
Published: June 2021

We previously reported that diet‐restriction rescued all the type 2 diabetes‐like phenotypes except for hyperinsulinemia in mice overexpressing the Se‐dependent glutathione peroxidase 1 (OE). This study was to determine effects of dietary Se deficiency on the metabolic phenotypes and related gene expression in pancreatic islets of the diet‐restricted OE mice over their wild‐type (WT) mice. Forty‐seven individually reared male OE and WT mice were fed Se‐adequate (0.4 mg Se/kg) or Se‐deficient (< 0.02 mg Se/kg) diet at 2 g/d starting at 4 wk of age for 2 wk, 2.5 g/d for the second 2 wk, and 3 g/d for another 8 wk. Dietary Se deficiency equalized the lower body weight of the Se‐adequate OE mice to that of the WT mice, but showed no significant effect on fasting plasma glucose concentration, body insulin or glucose tolerance or the glucose‐stimulated insulin secretion in either genotype. While the genotype effect (P < 0.05) was seen on islet mRNA levels of pdx1, beta2, p53, and glut2, dietary Se deficiency up‐regulated (P < 0.05) those of gk1, ins1, pdx1, preglucagon, and ucp2. There was a strong genotype and dietary Se interaction on islet mRNA levels of beta2, p53 and glut2. In conclusion, dietary Se deficiency affected the body weights and the islet mRNA expression of glucose metabolism‐related genes in the diet‐restricted OE and WT mice, but did not remove their genotype difference in hyperinsulinemia (NIH DK 53018).
Regular Grape Intake Reduces Cardiac and Renal Dysfunction and Metabolic Syndrome in Obesity‐Prone Rats
Authors: Seymour E Mitchell , Lewis Sarah K , Bolling Steven F , Bennink Maurice R
Published: June 2021

Metabolic Syndrome is characterized by increased systemic inflammation, abdominal fat, high triglycerides, low HDL, hypertension, and insulin resistance. The presence of some or all of these risk factors predisposes one to Type II diabetes and cardiovascular disease. Epidemiologic studies suggest that higher intake of fruits/vegetables could modify risk factors for metabolic syndrome. Phytochemicals may be vital to the observed health effects. Grapes are a rich, whole‐food source of phytochemicals. In the obesity‐prone Zucker Fatty rat, we tested the effect of a higher fat diet(45% kcal) with added whole table grape powder(3% w:w). Rats were fed for 90 days. Compared to a macronutrient and calorie‐matched control group, the grape diet had no significant effect on body weight or DEXA‐determined body composition. Grape intake reduced blood pressure and proteinuria while improving cardiac output. The grape‐fed group had reduced heart weight, kidney weight, and liver weight. The grape‐fed animals had reduced fasting serum triglycerides and hyperinsulinemia but not total cholesterol(p=0.12). Finally, grape intake reduced plasma inflammatory markers C‐reactive protein, TNF‐α and IL‐6, and reduced plasma oxidative stress marker 8‐isoprostane. The results suggest that regular intake of grapes reduced several risk factors for cardiovascular disease and metabolic syndrome.
Atherogenic effects of a high fat diet during pregnancy: examining the potential benefits of certain flavonoids using a mutant mouse model
Authors: Henderson Mary Nicole , Keen Carl L , Lanoue Louise
Published: June 2021

The fetal origins of health and disease describes the idea that maternal nutrition may alter the normal programming of development and result in an increased risk of metabolic diseases into adulthood. We used LDLr homozygous null (LDLr −/−) mice to examine whether maternal consumption of a high fat diet increases the risk for atherosclerosis in the progeny and to test if the addition of certain flavonoids mitigates this pro‐atherogenic effect. LDLr −/− female mice were fed a low fat (LF) or a high fat diet (HF), the HF diet supplemented with 1% epicatechin/catechin (4:1) (HFEC), or 1% rutin (HFRU) for 6 weeks prior to mating, through lactation. Dams were killed on gestation day (GD) 18.5 to determine fetal outcome. Tissues and plasma were collected and analyzed for lipid levels and markers of atherosclerosis, oxidation and inflammation. Preliminary results show that mice fed the HF diet have significant increased liver weight compared to the other dietary groups. Dams fed this diet also had litters with an increased number of resorptions, reduced number of significantly smaller GD 18.5 fetuses, which also exhibited greater rates of gross malformations; the addition of flavonoids ameliorated these reproductive outcomes. Our data show that flavonoids have a beneficial effect on fatty liver and improve the reproductive and developmental outcomes associated with a high fat diet. (Supported by the CA Vitamin Settlement Fund).
Global improvement in multiple cardiovascular disease risk factors with a medical food containing soy, phytosterols, hops rho iso‐alpha acids, and acacia proanthocyanidins and a Mediterranean‐style low glycemic load diet in women with metabolic syndrome
Authors: McIntosh Mark , Kalynych Colleen J , Vukich Clare , Kumar Vivek , Lott Michelle , Lerman Robert H
Published: June 2021

We evaluated effects on cardiovascular disease (CVD) risk factors of a Mediterranean‐style, low glycemic load diet (MLGD) alone or in combination with a phytosterol‐soy based medical food (PSS) containing hops rho iso‐alpha acids and acacia proanthocyanidins in women with metabolic syndrome (MetS). Subjects (BMI 25–45 kg/m2, LDL cholesterol (LDL‐C) ≥100 mg/dL, and TG≥150 mg/dL) were randomly assigned to either MLGD+PSS (n=12) or MLGD alone (n=12). No caloric restriction was imposed and exercise was maintained at baseline levels. Improvements in total cholesterol, LDL‐C, and apolipoprotein B (apo B) were noted in both arms (P<0.01). ApoB/apo A1 and insulin were reduced only in MLGD+PSS (P<0.01). Compared to MLGD, MLGD+PSS experienced greater reductions (P<0.05) in apo B at 8 and 12 weeks and in homocysteine at 12 weeks (p<0.05). LDL particle number was decreased at 8 (P<0.005) and 12 weeks (P<0.05) in MLGD+PSS; however, a reduction was found only at 8 weeks (P<0.05) in MLGD. Small LDL particles were decreased at 8 weeks (P<0.005) and trended downward at 12 weeks (p=0.06) only in MLGD+PSS. A downward trend in hsCRP was noted at 12 weeks, only in MLGD+PSS (P=0.07). Supplementation with a medical food containing soy, phytosterols, and specific phytonutrients may enhance benefits of a MLGD in women with MetS leading to global improvement in multiple CVD risk factors.

Supported by MetaProteomics, LLC.
Fat oxidation is enhanced in meals containing PUFA from walnuts
Authors: Tapsell Linda Clare , Batterham Marijka Jane , Tan Sze Yen
Published: June 2021

Polyunsaturated fats (PUFA) are preferentially utilized as fuel rather than stored. Diets containing PUFA rich foods (and perhaps also suitable food matrices) may be advantageous in promoting fat oxidation. Greater fat oxidation may lead to reduced fat mass, the target for weight loss. The aim of this study was to examine the effects on fat oxidation of a walnut based diet compared to a control with olive oil. In a crossover design testing effects of walnuts vs olive oil, 16 overweight adults consumed isocaloric breakfast and lunch meals based on core foods during 8hr in a room calorimeter facility. There was no difference in energy expenditure between the diet phases but fat oxidation was higher during the walnut period compared to the control (RQ for control 0.908 ± 0.046 vs walnut 0.855 ± 0.036, P = 0.029).Under acute conditions this result indicates that the walnut containing meals produced a more favorable fuel utilization profile for body fat loss. Further research would determine whether the acute fat oxidation effect translates to greater loss of body fat in the long term.

Source of research support: California Walnut Commission Project Grant.
Vitamin C deficiency in low‐income persons in the United States: 2003–2006 National Health and Nutrition Examination Survey (NHANES)
Authors: Schleicher Rosemary L , Carroll Margaret D , Lacher David A
Published: June 2021

Low‐income adults are at increased risk for vitamin C deficiency. NHANES 2003–2006 data were used to assess risk factors such as obesity, smoking, and/or low vitamin C intake. Income status was defined using the poverty‐income ratio (PIR), which was calculated by dividing family income by a poverty threshold that is specific for family size. Low, medium and high incomes were defined as PIR <1, 1 to <3, and ≥3, respectively. Trend analysis was used to test for significance. Low‐income adults were more likely to be vitamin C deficient than medium‐ or high‐income adults (OR: 1.4, 2.1; p<0.001) and equally likely to be obese as those with medium or high incomes (35%, 35%, 32%; p=0.11). Percent of adult smokers (serum cotinine >10 ng/mL) decreased linearly (41%, 31%, 25%; p<0.001) with increasing income category. Percent of adults with one‐day dietary intake of vitamin C < estimated average requirement (EAR) decreased linearly (61%, 58%, 55%; p<0.05) with increasing income category. Only 26% of low‐income adults used any vitamin C‐containing supplements in the previous 30 days compared with 39% of medium‐ and 53% of high‐income adults (p<0.001). Race/ethnicity, gender and age were also considered in a multiple logistic regression model. Poor diet, non‐use of vitamin C‐containing supplements, smoking and being non‐Hispanic white were major factors associated with vitamin C deficiency among low‐income persons (p<0.01).
Maternal autonomy and its influence on pregnancy outcome in India
Authors: Chakraborty Priyanka , Anderson Alex Kojo
Published: June 2021

Objective

This study aims to examine the influence of women's autonomy on pregnancy outcome (birth weight and birth size).

Method

This is a secondary data analysis of the 2005–2006 National Health and Family Survey (NFHS‐III) of India. Descriptive and logistic regression analyses were performed.

Result

The average age of women included in this study was 25.9 ± 4.9 years. Although, the mean birth weight was 2835 ± 666.4 g, nearly 20% of the index children were born LBW (<2500 g). Lower maternal age, illiteracy, poor socioeconomic status and rural households were significant predictors of both LBW and smaller birth size as reported by the mother. Interestingly, women with lower autonomy had a poor nutritional status (p < 0.001), and were more likely to deliver LBW (OR = 1.4, 95% CI = 1.2 − 1.6, p < 0.001) and small infants (OR = 1.5, 95% CI = 1.3 − 1.7, p < 0.001) as compared to women with a higher autonomy. Lower maternal autonomy remained a significant predictor (OR = 1.3, 95% CI = 1.1 − 1.5, p = 0.006) for both LBW and small size at birth (OR = 1.4, 95% CI = 1.2 − 1.7, p < 0.001), after controlling for maternal socio‐demographic characteristics, parity and birth interval.

Conclusion

Findings from this study suggest a strong association between maternal autonomy and pregnancy outcome with mothers with low autonomy having a higher risk of delivering a low birth weight baby and also reporting smaller birth size.

Funding: Dept of Foods & Nutr, UGA
Gender and folate intake affect choline dynamics and gene expression in mice consuming isotopically labeled choline.
Authors: Jiang Xinyin , Chew Tina , Yan Jian , Wang Wei , Carrier Bradley , Lusa Amanda , West Allyson , Malysheva Olga , Caudill Marie A
Published: June 2021

This study investigated the effects of folate intake, Mthfr deficiency, and gender on the fate of orally consumed choline and on the transcript levels of choline metabolizing genes. Mthfr +/+ or +/− mice (n=40; 20 nonpregnant female, 20 male; age 10 wk) were randomized to a folate sufficient or folate deficient diet for 8 wk during which modest amounts of labeled choline (d9‐choline; 1.6 mM), added to the drinking water, were consumed. Based on the concentrations of deuterium labeled choline metabolites in liver, gender robustly (P<0.01) affected choline flux. Compared to males, females had higher concentrations of d9‐phosphatidylcholine (PC, 1.5 times), d3‐PC (2 times), d9‐glycerophosphocholine (GPC, 4 times), d9‐betaine (2 times) and d6‐dimethylglycine (2 times). Female mice also expressed more PEMT in liver and kidney, more BHMT in kidney, and less BHMT in liver. Folate deficiency also influenced (P<0.05) choline dynamics in female mice with lower hepatic concentrations of d3‐PC and d9‐GPC. Increased expression (~3 times) of hepatic choline dehydrogenase and brain choline acetyltransferase was also observed in both genders. In contrast, Mthfr deficiency had subtle effects on choline metabolism; none of which achieved statistical significance. Taken together, these data show enhanced choline cycling and greater sensitivity to folate intake in nonpregnant female than male mice.

Grant Funding Source: Funded in part by NIH Grant No. S06GM053933 and the California Agricultural Research Initiative
Oral betaine supplementation restores ATP concentrations in choline dehydrogenase knockout mouse spermatozoa
Authors: Johnson Amy Rose , Zeisel Steven
Published: June 2021

Choline dehydrogenase (CHDH) converts choline to betaine, an important source of methyl groups for one‐carbon metabolism and an organic osmolyte. Deletion of the choline dehydrogenase gene in mice (Chdh−/−) leads to very low betaine concentrations in tissues, including testis, an organ that normally contains 10x more betaine than liver. Chdh−/− male mice are infertile due to diminished sperm motility that may be linked to the reduction of ATP in these cells. Feeding Chdh−/− male mice betaine via drinking water for the duration of one mouse spermatic cycle (42 days) increased testicular betaine concentrations and restored ATP concentrations to levels measured in Chdh+/+ and Chdh+/− spermatozoa (neither of which show impaired sperm motility or fertility). Sperm motility increased by 100% (from 15% progressive motility to 30% progressive motility), but was not fully restored to the level of Chdh+/+ and Chdh+/− mice (58% progressive motility) indicating that betaine plays an important role in sperm cell motility apart from normalizing ATP concentration, perhaps through its role as an osmolyte. Our data suggest that betaine is necessary for normal sperm cell function and men who carry functional mutations that decrease the activity of the CHDH enzyme may be more likely to have decreased fertility. This work is supported by grants from the NIH (AG09525, DK55865, DK56350). ARJ is supported by a scholarship from Balchem Corporation.

Grant Funding Source: National Institutes of Health (AG09525, DK55865, DK56350)
Transcriptional Regulation of the Menkes Copper ATPase (Atp7a) Gene by Hypoxia Inducible Factor (HIF) During Iron Deficiency
Authors: Xie Liwei , Collins James F.
Published: June 2021

Several intestinal genes are induced by HIF‐2α during iron deficiency, including divalent metal transporter 1 (Dmt1) and duodenal cytochrome B (DcytB). We previously observed that Atp7a was strongly upregulated in the duodenum of iron deficient rats. We thus sought to test the hypothesis that Atp7a is regulated by one of the HIFs during iron deprivation. To mimic hypoxia, rat intestinal epithelial (IEC‐6) cells were treated with CoCl2 or an iron chelator plus copper; both treatments led to induction of Atp7a mRNA expression. Cells were further exposed to low oxygen conditions, causing a ~4‐fold increase in Atp7a expression. To decipher the molecular mechanism of this induction, several Atp7a promoter fragments (ranging in size from 3000 to 50 bp) were PCR amplified and cloned into a firefly luciferase reporter vector. A 224 bp basal promoter fragment with full activity was identified, which contained evolutionarily conserved HIF binding sites. HIF‐1α and HIF‐2α over‐expression led to a significant increase in Atp7a promoter activity (2‐ and 4‐fold, respectively). Overall, this study demonstrates that Atp7a is regulated by HIF during iron deprivation, in parallel to other iron and copper related genes. Future experiments using chromatin immunoprecipitation (ChIP) and gel mobility shift assay are underway to determine precisely which HIF isoform (HIF‐1α or ‐2α) regulates Atp7a expression.

Grant Funding Source: 1R01 DK074867
Dietary iron affects mRNA expression of porcine copper transporters
Authors: Fry Robert Scott , Spears Jerry W , Hansen Stephanie L , Ashwell Melissa S
Published: June 2021

Weanling male pigs (21 days of age) were fed diets deficient (20 mg Fe/kg; L‐Fe), adequate (120 mg Fe/kg; A‐Fe) or high (520 mg Fe/kg; H‐Fe) in iron (Fe) for 32 days to evaluate the effects of dietary Fe level on copper (Cu) transporters and chaperones. Increasing dietary Fe increased Fe in proximal duodenum and liver. Liver Cu was lower in A‐Fe than in L‐Fe and H‐Fe pigs and did not differ among pigs fed L‐Fe and H‐Fe diets. Expression of liver copper transporter 1 (Ctr1) was higher in L‐Fe vs. A‐Fe pigs. Liver Atp7b was lower in both L‐Fe and H‐Fe pigs vs. A‐Fe pigs. Ceruloplasmin (Cp) expression in liver was up‐regulated in L‐Fe and H‐Fe pigs vs. A‐Fe pigs. Cp was also increased in pigs fed L‐Fe vs. H‐Fe diets. Feeding a L‐Fe diet tended to decrease Commd1 compared to feeding an A‐Fe diet. Liver cytochrome c oxidase assembly protein 17 (Cox17), antioxidant 1 (Atox1), copper chaperone for Cu/Zn superoxide dismutase (CCS), Cu/Zn superoxide dismutase (Sod1), and metallothionein 1a (Mt1a) were unaffected by dietary Fe. Duodenal Cu concentration and expression of duodenal Ctr1, Atox1, Cox17, CCS, Sod1, Atp7a, or Mt1a were not affected by dietary Fe. These data indicate that dietary Fe affects cellular Cu transporters involved in import and export of Cu to a greater extent in the liver than in duodenum. Reduced hepatic expression of Atp7b in both L‐Fe and H‐Fe pigs may explain the increased liver Cu seen in these pigs relative to A‐Fe.

Grant Funding Source: Micronutrients
Fibersol‐2 increases subjective and biochemical measures of satiety when ingested with a meal
Authors: Hendrich Suzanne , Ye Zhong , Arumugam Visalakshi , Haugabrooks Esther , Williamson‐Hughes Patricia
Published: June 2021

We hypothesized that Fibersol‐2 (FS‐2) would increase satiety, decrease hunger sensations, and affect appetite regulating hormones. Nineteen healthy subjects participated in a randomized, double‐blind, placebo controlled crossover study. FS‐2 treatments were examined under two conditions; tea with 0 or 10 grams of FS‐2 without a meal and 0, 5 and 10 grams of FS‐2 in tea with a standard meal. A visual analog scale (VAS) questionnaire was used to assess subjective appetite and satiety. Satiety‐related peptide hormones, ghrelin, PYY, GLP‐1, gastrin, GIP and insulin were measured by ELISA. AUCs for VAS indicated significantly greater satiety after the meal than after tea intake only. FS‐2 with a meal caused greater satiety measured as decreased desire to eat sweet or savory items, compared with intake only of control tea. GLP‐1 was significantly increased after the ingestion of a defined meal with 10g FS‐2 tea compared to the control tea not containing FS‐2. Appetite hormones PYY and GLP‐1 were significantly increased after the defined meal and tea containing 10g FS‐2 compared with the meal and control tea. Ghrelin was decreased by FS‐2 with a meal compared with ingestion of tea only. This study showed that FS‐2 administration stimulated production of specific satiety peptides such as PYY, decreased the hunger peptide ghrelin and enhanced satiety after a meal. Supported by Archer Daniels Midland.
Improved Postprandial Glycemia and Appetite Scores after Addition of the Ancient Grain Salba (Salvia Hispanica L.) vs Flax to an OGTT: Possible Effect of Viscosity
Authors: Vuksan Vladimir , Choleva Lauryn , Perrin‐Houdon Solenne , Rogovik Alexander , Fairgrieve Christopher , Jenkins Alexandra
Published: June 2021

Objective

To compare the effects of Salba and flax, two nutritionally similar, high fiber grains whose main difference is viscosity, on postprandial glycemia and appetite.

Methods

Using an acute randomized, single‐blind, crossover design, 9 healthy subjects (4M:5F; BMI 22.7±4 kg/m2) received, on 3 different occasions, a 50g glucose drink alone or with either 25g Salba or 31g flax added, which were matched for fiber. Capillary blood was taken and hunger questionnaires completed at fasting, 15, 30, 45, 60, 90 and 120 min post‐consumption. Viscosity was measured using a Brookfield Dial Viscometer.

Results

The viscosity of Salba was approximately 3 times higher than that of flax. Salba significantly reduced the glucose iAUC compared to control (p=0.049), whereas flax did not. Salba and flax consumption increased 2hr satiety scores compared to control by 83% and 55%, respectively (NS).

Conclusions

Addition of Salba, but not flax, to a glucose drink significantly lowers postprandial glycemia. Although Salba increased satiety to a greater extend than flax, this did not reach statistical significance. These preliminary data suggest that the greater effectiveness of Salba may be due to its higher viscosity level. Further research is warranted to assess the effects of Salba on postprandial glycemia and appetite control.

Research support: Salba Smart Natural Products, Denver, CO, USA.
Effect of viscosity and fermentability of purified non‐starch polysaccharides (NSP) on kinetics of net glucose and short chain fatty acids (SCFA) portal flux and insulin secretion in porto‐arterial catheterized pigs
Authors: Hooda Seema , Matte J Jacques , Vasanthan Thavaratnam , Zijlstra Ruurd T
Published: June 2021

The NSP may lower glycemic and insulin responses, but specific contributions of viscosity and fermentability are unknown. Thus, the effects of NSP on net nutrient portal flux and insulin responses were studied in 4 pigs with 2 catheters [portal vein, carotid artery] and 1 blood flow probe [portal vein]. Semi‐purified [cornstarch, casein] diets supplemented with 5% purified NSP sources were fed in a 2 (low, high viscous; V) × 2 (low, high fermentable; F) factorial arrangement using: low V, low F cellulose (CEL1), high V, low F carboxymethylcellulose (CMC), low V, high F cellulose (CEL2), and high V, high F oat β‐glucan (HVG). Blood was sampled for 12 h postprandially and net nutrient portal flux and insulin secretion were calculated from plasma portal‐arterial differences × flow. Blood flow, portal and carotid glucose and net glucose portal flux peaked at 45 min after feeding (P<0.001) and were not affected by NSP. However, fermentable NSP (CEL2 and HVG) increased (P<0.05) net glucose portal flux 46% over 12 h postprandially. Insulin secretion was 44% lower (P<0.05) for viscous than non viscous NSP. The CEL2 and HVG diets increased (P<0.05) net SCFA portal flux for propionate and butyrate 48%, indicating increased colonic fermentation. In conclusion, viscosity of NSP reduced insulin secretion and fermentable NSP increased net portal flux of glucose, propionate, and butyrate.

Grant Funding Source: ALMA, Danisco, and Alberta Pulse Growers
Regulatory Role of Mucosal Maltase‐Glucoamylase in Starch Digestion and Glucose Homeostasis
Authors: Diaz‐Sotomayor Maricela , Avery Stephen E , Chacko Shaji K , Quezada‐Calvillo Roberto , Yan Like , Hamaker Bruce R , Nichols Buford L
Published: June 2021

Slower rates of starch digestion by sucrase‐isomaltase (Si) in Mgam null mice may fail to regulate gluconeogenesis (GNG). Mgam nulls have 40% reduction of glucose production from starch.

Aim

Measure glycemic index and rate of gluconeogenesis (fGNG) as fraction of total glucose appearance (Ra) and glucogenesis from starch (MPE) by Mgam null and WT mice.

Methods

Groups of 4–8 null or WT mice were on low 13C‐diet and trained to feed from 12–13 h after previous feed (hAF). D2O was given IP at 2 hAF. 13C‐enriched starch was fed from 12–12.5 or 13 hAF and intake weighed. Blood was obtained by tail nicking at 5, 12, 12.5, 13, 14, and 16 hAF and decapitation at 14 or 16 hAF. Blood glucose was by glucometer and spotted on filter paper for MS. Glucose was derivatized as penta‐acetate and run by GC‐C‐IRMS for 13C‐glucose (MPE) and for 2H‐C5‐glucose (fGNG) enrichments by GC‐MS. Body D2O dilution was by IRMS.

Results

Inverse correlation between MPE and fGNG was found (R‐Sq 86%). At 14 hAF 0.5, but not 1.0 g, feeds, WT MPE exceeded null (p 0.02). Fasted fGNG averaged 71% and when fed null fell to 30% and WT to 20% (p 0.03). 1 gm intakes increased MPE only of null consistent with known in‐vitro substrate inhibition of Mgam.

Summary: Mgam activity regulates fGNG and is critical for starch digestion at snacking (0.5 g) but not at feasting (1 g) intakes. Mgam deficiency was compensated by increased fGNG. Glycemic index was regulated both by MPE and GNG pathways.
Dentin matrix protein 1 induces endothelial cell cycle arrest and differentiation through VE‐cadherin
Authors: BELLAHCENE Akeila , Pirotte Sophie , Mottet Denis , Ormenese Sandra , Castronovo Vincent
Published: June 2021

Dentin matrix protein 1 (DMP1) is a member of the Small Integrin‐Binding LIgand N‐linked Glycoproteins (SIBLINGs) family, a group of proteins initially described as mineralized extracellular matrices components and more recently implicated in several key steps of cancer progression, including angiogenesis. Although pro‐angiogenic activities have been demonstrated for two SIBLINGs, the role of DMP1 in angiogenesis has not been addressed yet. We found that DMP1 inhibited the proliferation while it stimulated migration and tubulogenesis of human umbilical vein endothelial cells (HUVEC), thus promoting differentiation of endothelial cells. Further investigation of DMP1 mechanism of action evidenced a CD44‐dependent G1‐block and an increased p27Kip1 and VE‐cadherin expression in HUVEC.

Our data identify DMP1 as a new regulator of angiogenesis that turns on the switch of the endothelial cell phenotype from proliferative to differentiated, through a CD44‐dependent differentiation program that links up with a VE‐cadherin pathway mediating contact inhibition of endothelial cell growth.
Targeting Angiogenesis: A therapeutic approach using a synthetic derived peptide
Authors: Yates Cecelia Christina , Jaynes Jesse , Wells Alan , Bodnar Richard , Turner Timothy
Published: June 2021

Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well‐orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that endothelial cells express CXC receptor 3 (CXCR3) late in wound regeneration, and upon ligandation by IP‐10 (CXCL10) new vessels are prevented and immature vessels involute. To develop new therapeutic agents to inhibit or collapse blood vessel formation and/or involution of newly forming vessels we isolated a 21 amino acid fragment, residues 78–98, which we modeled to be the functional domain of IP‐10 (IP10p) and analyzed its ability to modulate endothelial cell tube formation. Treatment of the endothelial cells with the IP‐10 peptide significantly inhibited VEGF‐induced endothelial motility and tube formation, a response critical for angiogenesis. [Using an in vivo Matrigel assay we show that the IP‐10p is able to inhibit vessel formation and induce vessel dissociation] Furthermore, stimulation of CXCR3 by the IP‐10 or the IP‐10 peptide induced an increase in cAMP production and activation of PKA that leads to the inhibition of VEGF‐mediated m‐calpain activation and thereby limits cell motility. We propose that this peptide provides a novel reagent that inhibits endothelial signaling pathway thus, allowing for the modulation angiogenesis.
Wrapping and Tapping Anastomosis between Engrafted Endothelial Networks and Host Vasculature
Authors: Munn Lance L , Liao Shan , Wong Hon Kit , Lacorre Delphine , di Tomaso Emmanuelle , Au Patrick , Fukumura Dai , Jain Rakesh K , Cheng Gang
Published: June 2021

A major obstacle in tissue engineering is poor post‐implantation cell survival due to the lack of blood perfusion. One approach is to populate the graft before implantation with endothelial or progenitor cells that can quickly organize into a network and connect with the host vasculature to achieve blood perfusion. Many types of endothelial and endothelial progenitor cells are capable of this, but the mechanism by which the implanted vascular networks anastomose with the host vasculature is unknown. Here we show that it occurs through a previously unreported process of “wrapping and tapping” (WAT). At the host‐implant interface, implanted ECs wrap around nearby host vessels, cause host vessel regression by disrupting their pericytes and basement membrane, and then completely replace segments of host vessels to divert flow into the contiguous, engrafted vascular network. This process is facilitated by high levels of MMP‐14 and MMP‐9 expressed specifically by wrapping ECs. Our results provide mechanistic understanding on this critical step of vascularization and may have implications for other physiological and pathological processes involving post‐natal vasculogenesis.
Interstitial flow induces vascular SMC migration in collagen I gels regulated by MMP‐1 via an ERK1/2‐dependent and c‐Jun‐mediated mechanism
Authors: Shi Zhong‐Dong , Tarbell John M
Published: June 2021

Smooth muscle cells (SMC) migration into the intima after vascular injury is a central process in vascular lesion formation. The transmural interstitial flow is observed after damage to the vascular endothelium. In this study, the direct effects of interstitial flow on SMC migration were investigated in a 3‐dimensional collagen I gel system.

Exposure of gels to a differential pressure of 1 cmH2O induced interstitial flow (shear stress ~0.05 dyn/cm2) that substantially enhanced cell migration rate. Gene silencing suggested that flow‐induced migration was controlled by matrix metalloproteinase (MMP)‐1. PD‐98059, an ERK1/2 inhibitor, completely abolished flow‐induced migration and MMP‐1 expression. PD‐98059 also inhibited flow‐induced ERK1/2 activation and c‐Jun and c‐Fos expression. Silencing ERK1/2 or c‐jun completely abolished SMC migration and/or MMP‐1 expression, while knocking down c‐fos did not affect MMP‐1 expression. We also found that p38 MAPK and NF‐κB did not play major roles in flow‐induced MMP‐1 expression and cell migration.

Taken together, our data indicate that interstitial flow induces MMP‐1 expression which in turn digests collagen matrix and promotes SMC migration via an ERK1/2‐dependent and c‐Jun‐mediated mechanism and suggest that interstitial flow may play an important role in SMC migration and neointima formation. Supported by NIH NHLBI grant RO1 HL 57093.
Roles of NF‐kB and STAT3 in CXC chemokine‐mediated hepatocyte proliferation and cell death
Authors: Clarke Callisia N , Sakai Nozomo , Tevar Amit D , Edwards Michael J , Lentsch Alex B
Published: June 2021

BACKGROUND

CXC chemokines have divergent effects on hepatocytes. After hepatic I/R CXC chemokines are expressed at high levels and promote liver injury. After partial hepatectomy, they are expressed at low levels and promote proliferation. Previous studies show that chemokines are proliferative at all doses, hepatoprotective at low concentrations, while cytotoxic at high concentrations. Here we explore the roles of NF‐kB and STAT3 in regulating the effects of CXC chemokines in hepatocytes.

METHODS

Hepatocytes isolated from Balb/c mice were stimulated with media alone, or with MIP‐2 at low (10 ng/ml) or high (10,000 ng/ml) concentrations in the presence or absence of inhibitors of NF‐kB (BAY 11‐7085) or STAT3 (AG490) for 24 hrs. Cell death was determined by release of LDH and cell proliferation by DNA incorporation of BrdU.

RESULTS

Stimulation of hepatocytes with low dose MIP‐2 resulted in decreased cellular injury and increased proliferation. Blockade of NF‐kB resulted in massive hepatocyte cell death. Blockade of STAT3 resulted in abrogation of the protective effects of low‐dose MIP‐2. Blockade of STAT3 resulted in a decrease in hepatocyte proliferation with or without MIP‐2.

CONCLUSIONS

NF‐kB activation is required for hepatocyte viability in vivo. The hepatoprotective effect of low concentrations of CXC chemokines is STAT3 dependent. STAT3 is required for hepatocyte proliferation in vitro.
Immunodeficient mice ‐ A suitable model for cell transplantation in non‐alcoholic steatohepatisis (NASH)
Authors: Stock Peggy , Pelz Sandra , Ebensing Sabine , Hempel Madlen , Brückner Sandra , Richter Kati , Christ Bruno
Published: June 2021

NASH is a benign disease and will progress, if untreated, into fibrosis/cirrhosis and potentially into HCC. Human cell therapy approaches for the treatment of NASH have not been addressed yet. The present work aimed at establishing an animal model to evaluate the feasibility of stem cell‐derived hepatocytes.

Immunodeficient Pfp/Rag2−/− mice were fed a methionin‐cholin‐deficient diet (MCD diet) up to 5 weeks. Alanine aminotransferase (ALT) and triglycerides were determined in the serum. Histological analyses of liver sections were performed to detect structural abnormalities by HE, the collagen distribution by sirius‐red and fat depositions by sudan III staining. Expression of the acute phase protein SAA, the proinflammatory cytokine TNFα, the marker for activated stellate cells αSMA as well as collagen1 in liver tissue were specified by RT‐PCR.

Already 3 weeks after feeding the MCD diet, microsections displayed a deteriorated architecture of the liver tissue, which worsened with continued feeding. By HE‐staining massive steatosis and hepatocellular injury were observed and confirmed by sudan III staining in livers of animals fed the MCD diet as compared to animals fed the control diet. Fibrosis in livers of animals on MCD diet was obvious by collagen staining. The marker of hepatocyte fade ALT was significantly higher (2‐fold) in the serum of mice on MCD diet. Serum triglycerides were significantly lower in MCD diet‐fed animals. RT‐PCR analysis revealed elevated mRNA levels of SAA and TNFα as well as of αSMA and collagen1 in the livers of mice fed the MCD diet.

Thus, immunodeficient Pfp/Rag2 mice fed with the MCD diet displayed typical features of NASH, which makes this animal model suitable to evaluate pre‐clinically human cell therapy approaches of liver diseases.
Almost human: the fossils of early Homo
Authors: Grine Frederick E.
Published: June 2021

The earliest fossils of our genus date to 2.5 ‐ 2.0 million years ago (Ma) in Africa, but are so rare and anatomically limited as to reveal little about the nature of its origin beyond an association with a fluctuating trend towards more open, wetter environments. There are various claimants for Homo ancestry, but a taxon resembling Australopithecus africanus provides the best candidate for this root node. Between 2.0 ‐ 1.5 Ma, the fossil record is significantly better. Specimens are attributed to three taxa – Homo habilis, H. rudolfensis and H. erectus. Appreciation of the locomotor anatomy of H. habilis and H. rudolfensis is hampered by the lack of associated, relatively complete specimens. This anatomy is better known for H. erectus. Homo habilis retains features suggestive of frequent arboreality. Homo erectus was an obligate terrestrial biped; some features may have been associated with long distance running ‐ a valuable attribute for hunting/scavenging – but others seem to be inconsistent with running or throwing behaviors. Homo erectus was more similar to chimpanzees than to H. sapiens in the timing of life history parameters. Early Homo molars tend to be narrower and with more occlusal relief than those of earlier hominins; occlusal microwear suggests a diverse diet that included tough foods. The manufacture and use of stone tools in foraging appear to have been early attributes of our genus.
Genetic basis for collateral circulatory insufficiency
Authors: Faber James E
Published: June 2021

Native (pre‐existing) collaterals are rare arteriole anastomoses that interconnect two adjacent arterial trees, thus serving as endogenous bypass vessels. Despite their importance, nothing is known about when or how these vessels form. Furthermore, recent evidence indicates that the density and diameter of collaterals in tissues of healthy mice and humans evidences remarkable variation from as yet unknown mechanisms. This presentation will summarize evidence in mice for the following: The collateral circulation develops late embryonically and undergoes maturation early postnatally. Natural genetic variation exerts a profound effect on both processes, and on collateral remodeling in obstructive disease. This variation results in equally wide variation in the severity of tissue injury in models of stroke and peripheral artery disease. Several genes impacting collateral formation and remodeling have been identified. In addition, genome‐wide mapping studies have identified novel genetic loci and candidate genes linked to variation in collateral abundance. It is anticipated that identification of genetic polymorphisms affecting the native collateral circulation will lead to an understanding of the pathways controlling its formation, identify mechanisms underlying its wide variation, and possibly provide a means to predict risk‐severity for ischemic injury should obstructive disease develop.