bluuebunny/crossref_metadata_2025_split huggingface dataset:
The micronutrient profile of the typical American diet enhances colorectal carcinogenesis in mice (123.4)
Authors: Benninghoff Abby , Monsanto Stephany , Larson Deanna , Hintze Korry , Ward Robert , Lefevre Michael 
Published: June 2021

The new total Western diet (TWD) for rodents mimics typical human dietary intakes of macro‐ (carbohydrates, proteins, and fats) and micronutrients (vitamins and minerals) on an energy density basis for rodents. The objective of this study was to determine the impact of TWD on colorectal carcinogenesis using the azoxymethane + 1% dextran sodium sulfate mouse model of inflammation‐associated colon cancer. We compared colon cancer incidence, multiplicity and size in TWD‐fed mice to those provided a commercial 45% fat diet‐induced obesity diet and AIN93G, which is optimized for rodent health. Also, we included two additional test diets to evaluate the contribution of the micronutrient (vitamin‐ and mineral‐modified diet, [VMM]) or macronutrient (macro‐modified diet [MM]) contents of the TWD. Consumption of the TWD or VMM diet significantly increased colon tumor multiplicity by 2‐fold and size by more than 3‐fold compared to the AIN93G control (p<0.01), whereas consumption of the DIO or MM diets did not enhance colon tumorigenesis. Collectively, these observations point to a critical role of dietary micronutrients in colon carcinogenesis. Importantly, this promoting effect is likely unrelated to the metabolic syndrome phenotype induced by the high fat diet, as our prior data showed that TWD did not alter body composition, body weight gain or glucose tolerance. Moreover, our observations emphasize the need to take into account the micronutrient content of rodent basal diets when modeling typical U.S. nutrition in pre‐clinical animal experiments in order to improve the translation of these studies to human nutrition and dietary intervention programs. We are currently performing genome‐wide analysis of gene expression in colon mucosa obtained from control‐, TWD‐ and DIO‐fed mice. Also, an additional diet trial using the APCmin genetic mouse model of intestinal cancer is underway to confirm our observations.Grant Funding Source: Supported by the Utah Agricultural Experiment Station
Usual dietary energy density distribution is associated with excess body weight in Mexican children (130.3)
Authors: Aburto Tania , Cantoral Alejandra , Hérnandez‐Barrera Lucia , Carriquiry Alicia , Rivera Juan 
Published: June 2021

Studies suggest a positive association between dietary energy density (DED) and body weight. Evidence in children is inconclusive. Our objective was to compare usual DED distributions of non‐overweight and overweight children adjusting to minimize random and systematic errors.We used 24 hour recall data from 2367 children between 5 and 11 y old from the 2012 National Health and Nutrition Survey. Repeated measures of 24 h recalls were obtained in a random sample (10%) to estimate usual intake distributions using the Iowa State University method. Implausible dietary reports were identified. The relationship between DED and body weight status was evaluated using multivariate linear regression models.35.1% of the children in the sample were overweight (including obesity). After adjustment for covariates, DED of overweight children was 2.9 kcal/100g higher than that of non‐overweight children (p=0.066). Adjusting also for measurement error and restricting analysis to plausible reporters, DED was 9.2 kcal/100 g higher in overweight compared to non‐overweight children (p<0.0001).Results show a positive association between DED and body weight in Mexican children and the importance of appropriate adjustments for random and systematic errors in dietary associations. They also suggest the need of strategies to reduce DED, such as a tax on energy‐dense low‐quality foods to tackle obesity in Mexico.
Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) (130.6)
Authors: Mossavar‐Rahmani Yasmin , Shaw Pamela , Wong William , Sotres‐Alvarez Daniela , Gellman Marc , Van Horn Linda , Stoutenberg Mark , Daviglus Martha , Wylie‐Rosett Judith , Siega‐Riz Anna Maria , Ou Fang‐Shu , Prentice Ross 
Published: June 2021

Objective: In SOLNAS we investigate measurement error in self‐reported diet of Hispanics in the US by ethnicity (Cuban, Dominican, Mexican, Puerto Rican, Central and South American) who are prone to obesity and related co‐morbidities.Methods: In 485 participants aged 18‐74 yrs, doubly labeled water and urinary nitrogen were used as objective biomarkers of energy and protein intake, respectively. Self‐report was captured from two 24‐hour dietary recalls (24HR). We estimate the bias of 24HR with multivariate regression.Summary: Energy intake was underestimated on average 24.1% (men 20.5%; women 26.2%) and protein by 15.9% (men 11.6%; women 18.4%). Participant characteristics associated with underestimation of energy were higher BMI, being female, older age and Hispanic ethnicity. For protein, these characteristics were higher BMI, older age, being a non‐smoker, Spanish speaking and Hispanic ethnicity.Conclusions: There is systematic under‐reporting of energy and protein intake that varies significantly by Hispanic ethnicity and language preference. Calibration equations that correct for subject‐specific error in reporting can reduce bias in diet‐disease associations.Grant Funding Source: Supported by NIH/NHLBI grant #5 R01 HL095856
Vegetarian and non‐vegetarian dietary patterns and nutrient profile differentials between the sexes and Blacks and Whites (130.7)
Authors: Rizzo Nico , Fraser Gary 
Published: June 2021

Background: Dietary patterns are of great interest as they reflect choices of food combinations over time and may contribute to the development or prevention of disease.Objective: To compare nutrient intakes of diverse dietary patterns between races and sexes.Design: Cross‐sectional study of 71751 subjects (mean age 59 years, 65% women, 76% white) from the Adventist‐Health‐Study‐2. Data was collected between 2002 and 2007. Participants completed a 204‐item validated semi‐quantitative food frequency questionnaire. The dietary patterns compared are: non vegetarian, semi vegetarian, pesco vegetarian, lacto‐ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns stratified by sex and race.Results: Nutrient intakes varied more strongly between dietary patterns than between the sexes or blacks and whites. Nutrient intakes were more dissimilar between blacks and whites than between the sexes. Blacks hada higher proportion of non vegetarians and pesco vegetarians. Supplement intakes were markedly higher in women than in men and higher in whites than in blacks. Blacks had lower intakes of nutrients often associated with dairy products and higher intakes of soy protein and marine fatty acids.Conclusions: Dietary patterns characterized by differences in meat and dairy consumption show marked differences in nutrient composition that can have health implications. Differences between the sexes and black and white subjects should be considered when interpreting demographic differences in nutritional studies.Grant Funding Source: Supported by National Institutes of Health Grant 1R01‐CA‐94594
Differences between the ex vivo and in vivo anti‐inflammatory activities of Aronia mitschurinii (black chokeberry) polyphenols in C57/BL6 mice (134.3)
Authors: Bolling Bradley , Brand Mark , Draghi Andrew , Martin Derek 
Published: June 2021

The objective of this study was to characterize the anti‐inflammatory potential of Aronia mitschurinii ‘Viking’ (black chokeberry). Male C57/BL6 mice were fed AIN‐93 chow or chow supplemented with 4.5% lyophilized aronia ad libitum for 4 wk. Primary mouse splenocytes were also incubated with aronia extract or its polyphenol constituents ex vivo. IL‐6 and IL‐10 were determined by ELISA analysis of cell‐culture supernates. Aronia extract, quercetin, and cyanidin‐3‐arabinoside co‐incubation inhibited LPS‐stimulated splenocyte IL‐6. In contrast, there was no difference in LPS‐stimulated splenocyte IL‐6 production as a result of aronia feeding. Quercetin and hydroxycinnamic acids co‐incubation inhibited LPS‐stimulated splenocyte IL‐10. Aronia extract co‐incubation increased unstimulated splenocyte IL‐10 to 140% of the control. Similarly, colonic tissue IL‐10 was 101% greater in aronia‐fed mice than control. In contrast, aronia supplementation did not inhibit LPS‐induced colonic IL‐10, IL‐6, IL‐17 or TNF‐α. Therefore, although aronia polyphenols exhibit distinct structure‐function anti‐inflammatory activity in vitro in splenocytes, these actions are not realized after aronia feeding in healthy mice. However, aronia feeding may benefit colons of healthy mice by increasing IL‐10.Grant Funding Source: Supported by the University of Connecticut Diet and Health Initiative and USDA Hatch CONS0080
Developmental exposure to maternal folic acid intake programs vascular NADPH oxidase expression in mice (135.3)
Authors: Aleliunas Rika , Golbidi Saeid , Olson Jesse , Glier Melissa , Laher Ismail , Devlin Angela 
Published: June 2021

Nutritional adversity during development influences the cardiometabolic adaptation in adulthood. Recent birth cohort studies from South Asia have reported an association between maternal folate and vitamin B12 imbalance and increased child adiposity and insulin resistance. In Canada, where folic acid fortification was implemented in 1998, women have adequate folate status but 1 in 20 may be vitamin B12 deficient in the early stages of pregnancy. The goal of our project was to determine the effects of developmental exposure to high folic acid and low vitamin B12 status on vascular function. Female wild‐type C57BL/6J mice were fed diets high in folic acid, with (HFA+B12) and without (HFA‐B12) adequate vitamin B12, or a control diet for six weeks prior to breeding, and during pregnancy and lactation. Offspring were weaned onto control or a western diet (WD), consisting of 45% fat and 35% carbohydrate, and fed for 20 weeks. We assessed vascular endothelial function and NADPH oxidase subunit (Nox2) expression as indicators of vascular health. Mesenteric arteries from WD‐fed mice with developmental exposure to HFA‐B12 showed decreased relaxation (10%) in response to acetylcholine relative to control and HFA+B12 groups. In the control diet group basal nitric oxide production was lower (10%) in mice with developmental exposure to HFA (with and without vitamin B12). Nox2 subunit expression was decreased in aortae of mice with developmental exposure to high folic acid in both control‐fed and WD‐fed mice. These findings suggest that the developmental exposure to high maternal folic acid programs vascular health in adult offspring mice.Grant Funding Source: NSERC
Vitamin B12 status in pregnant women and their children in India (135.6)
Authors: Finkelstein Julia , Kurpad Anura , Thomas Tinku , Bose Beena , Samuel Tinu , Srinivasan Krishnamachari , Duggan Christopher 
Published: June 2021

Objective: To examine the prevalence and determinants of poor infant vitamin B12 status at birth, and determine the associations between maternal and infant vitamin B12 status.Methods: 366 pregnant women participating in a vitamin B12 supplementation trial in India were monitored to assess maternal vitamin B12 status in pregnancy and its association with infant vitamin B12 status at 6 weeks of age. Binomial and linear regression were used to evaluate the associations between maternal and infant vitamin B12 status.Results: 51% of mothers were vitamin B12 deficient (<150pmol/L) at baseline, and 47% of infants were vitamin B12 deficient at 6 weeks of age. Maternal vitamin B12 concentrations during 3 trimesters (T) were significantly correlated with infant vitamin B12 status (T1: r=0.19, p=0.10; T2: r=0.39, p<0.01; T3: r=0.56, p<0.0001); with stronger correlations in B12‐supplemented women (T1: r=0.42, p<0.01; T2: r=0.55, p<0.001; T3: r=0.55, p=0.001). After adjusting for vitamin B12 supplementation, higher maternal B12 concentrations at baseline predicted increased infant vitamin B12 levels (p=0.06), and infants born to vitamin B12‐deficient mothers were 1.6 times more likely to be vitamin B12 deficient (p=0.05).Conclusions: Inadequate maternal vitamin B12 status during pregnancy predicted increased risk of infant vitamin B12 deficiency.Grant Funding Source: Supported by: NICHD, ICMR
Modulation of paternal B vitamin intake does not affect tumorigenesis but does alter growth trajectory in Apc1638N mouse offspring (137.7)
Authors: Sabet Julia , Mason Joel , Bronson Rodrick , Crott Jimmy 
Published: June 2021

Modulation of paternal B vitamin intake does not affect tumorigenesis but does alter growth trajectory in Apc1638N mouse offspring Sabet JA1,2, Mason JB1,2, Bronson RT3, Crott JW1,21Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA2Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA3Rodent Histopathology Core, Harvard Medical School, Boston, MA It is well established that maternal nutrition can impact on offspring health and physiology; however the contribution of paternal nutrition to offspring health is less understood. We have shown that maternal B‐vitamin supplementation suppresses, while deficiency promotes, intestinal tumorigenesis in a mouse model of colorectal cancer. We sought to determine whether modulating paternal intake of vitamins B2, B6, B12, and folate similarly alters intestinal tumorigenesis in offspring. Male APC1638N mice were fed diets containing control, deficient, or supplemental quantities of vitamins B2, B6, B12, and folate for 8 wk before mating with control‐fed wild‐type females. APC1638N offspring were maintained on control diets until 28 wk of age. No differences in tumor incidence, size or grade were found between offspring of different paternal diet groups. Overall, male offspring exhibited a greater tumor incidence and burden than female offspring. Among female offspring, growth was significantly retarded in the progeny of deficient and supplemented fathers compared to control fathers. Modulation of paternal B‐vitamin intake prior to mating did not alter offspring intestinal tumorigenesis but did impact offspring growth in a sex‐specific fashion in APC1638N mice. Analyses to profile DNA methylation changes in sperm and gene expression changes in offspring liver are underway.Grant Funding Source: Supported by NCI grant 1 R03CA162505‐1
Characterization of a hepatocyte nuclear factor 4 alpha gene signature in hepatocellular carcinoma (144.11)
Authors: Walesky Chad , Gunewardena Sumedha , Yoo Byunggil , Li Ren , Edwards Genea , Apte Udayan 
Published: June 2021

Previous studies from our laboratory using conditional knockout mice and functional genomics have shown that HNF4α inhibits hepatocyte proliferation and deletion of HNF4α promotes DEN‐induced hepatic tumors in mice. To further delineate the role of HNF4α in hepatic tumorigenesis, we performed RNA‐seq analysis on DEN‐induced HCCs obtained from HNF4α‐null, WT, and normal mouse liver tissue. A total of 2152 genes were differentially expressed in HCC obtained from HNF4α‐null mice. Comparative genomics analysis of RNA‐seq data with HNF4α ChIP‐seq data revealed a novel gene signature for tumors lacking HNF4α. This analysis revealed 322 genes, which were at least 2‐fold differentially expressed and contained a putative HNF4α binding site. We hypothesize that liver tumors that lack HNF4α activity tend to be highly aggressive and metastatic. We tested this hypothesis using the HNF4α gene signature to characterize the HNF4α activity status in various mouse models of HCC and are currently conducting a prospective analysis of human HCC samples. Our results have revealed a novel set of genes regulated by HNF4α specifically involved in HCC pathogenesis that may be useful as a prognostic tool in HCC diagnosis.Grant Funding Source: Supported by NIH Training Grant T32 ES007079
Alveolar macrophages mediate release of mtDNA damage‐associated molecular patterns in Pseudomonas aeruginosa‐challenged rat lungs (145.6)
Authors: Kuck Jamie , Obiako Boniface , Pastukh Viktor , Gillespie Mark 
Published: June 2021

Oxidative mitochondrial DNA (mtDNA) damage and release of mtDNA damage‐associated molecular patterns (mtDNA DAMPs) may contribute to bacteria‐induced lung injury. The cellular mechanism by which bacteria trigger mtDNA DAMP formation is unknown. We tested whether P. aeruginosa causes alveolar macrophage‐dependent release of mtDNA DAMPs and attendant degradation of alveolar‐capillary barrier function. To deplete alveolar macrophages, rats were given an intratracheal injection of liposome‐encapsulated clodronate or liposomes alone 24 hours prior to experiments. Lungs isolated, mechanically ventilated, and buffer‐perfused were challenged with intratracheal instillation of P. aeruginosa (Strain 103). The vascular filtration coefficient was measured 15 min after challenge. Amplification of 200 bp sequences via RT‐PCR was used to measure accumulation of mtDNA DAMPs or bacterial DNA in perfusion medium. Rat lungs treated with vehicle had increased permeability, whereas those treated with clodronate showed no increases in the vascular filtration coefficient or accumulation of mtDNA DAMPs in perfusate 15 minutes after PA103 challenge. These observations suggest that alveolar macrophages are critical for P. aeruginosa‐induced formation and release of mtDNA DAMPs into the pulmonary circulation and attendant changes in lung endothelial permeability.Grant Funding Source: Supported by NIH
Adverse cardiac remodeling mediated by the altered expression of versican (15.7)
Authors: Mjaatvedt Corey , Burns Tara , Escobar Patricia , Ansarizadeh Yosef , Le Saux Claude 
Published: June 2021

Adverse remodeling following myocardial infarction (MI) is the primary pathologic process that leads to heart failure. The process is driven by normal repair mechanisms that become uncontrolled. This research focuses on the functional significance of the extracellular matrix molecule versican (Vcan) in regulating adverse remodeling and the deposition of insoluble fibrillar collagen outside of the infarct border zone. Our hypothesis is that adverse remodeling is mediated by an aberrant increase in Vcan deposition that promotes an increased presence of fibrocytes, cells expressing myeloid origin CD45+ and Hsp47+, into the injured as well as non‐inured myocardium. To test this hypothesis, we have experimentally induced MI by coronary ligation and compared WT, Vcan deficient (Vcan(tim1Zim)) and Cav1 null (a model of adverse remodeling) mice for expression of Vcan and the presence of fibrocytes within the injured and non‐injured myocardium. We show that in the WT Vcan is up regulated as part of the normal repair at the infarct borders. This expression pattern is accompanied by an increased infiltration of CD45+ cells within the Vcan rich boarder zone. Interestingly, in the Vcan depletion model, we measured significant reduced average injured wall thickness (247 vs. 394 µm), less infiltration of fibrocytes and an unexpected reduction of collagen deposition. In Cav1 null mice, Vcan is up regulated leading to a more widespread distribution of fibrocytes, associated with adverse remodeling after MI. A better understanding of adverse remodeling after MI will contribute to the development of extracellular matrix based interventions designed to reduce or prevent the morbid effects of post‐infarction remodeling.Grant Funding Source: NHLBI R01HL66231 (CHM), Janey Briscoe Center for Excellence in Cardiovascular Research (CJLS)
Excess endoplasmic reticulum is degraded by p62‐mediated selective autophagy in mammals (151.6)
Authors: Ding Wen‐Xing , Yang Hua , Ni Hong‐Min 
Published: June 2021

Liver is the most vital and dynamic organ, and is the major site for the metabolism and detoxification of xenobiotics. The cytochrome P450 enzymes (CYPs), which are synthesized and localized in the endoplasmic reticulum (ER), are the most important enzymes responsible for the drug metabolism in the liver. It is known that there is increased ER proliferation and induction of CYPs to meet the needs of metabolism in response to several xenobiotics. Whether autophagy is essential for the removal of excess ER following xenobiotic‐induced ER proliferation and induction of CYPs, and whether an autophagy receptor is involved in this selective process in mammals remains elusive. In the present study, using GFP‐LC3 transgenic and liver‐specific Atg5 knockout mice, we show that autophagy is essential for the removal of excess ER after treatment with the hepatic mitogen TCPOBOP (t1, 4‐bis [2‐(3, 5‐dichloropyridyloxy)] benzene). In addition to regulating ER degradation, our results also suggest that autophagy plays a role in regulating the homeostasis of hepatic CYPs. Furthermore, we also show that p62/SQSTM1, an autophagy receptor that has been shown to be involved in many selective types of autophagy, may act as an autophagy receptor for selective erphagy. Taken together, our results indicate that autophagy is essential for selective removal of excess ER and hepatic CYP enzymes in mouse livers.Grant Funding Source: Supported by NIAAA R01 AA020518; 5P20RR021940‐07; 8 P20 GM103549‐07
Exogenous expression of the Entamoeba histolytica adhesion protein EhADH112 in MDCK cells facilitates parasite invasion by altering tight junctions (152.1)
Authors: Betanzos Abigail , Cuellar Patricia , Azuara‐Liceaga Elisa , Bañuelos Cecilia , González‐Mariscal Lorenza , Schnoor Michael , Orozco Esther 
Published: June 2021

Entamoeba histolytica is the causative agent of human amoebiasis. Infection is initiated by interaction of the pathogen with intestinal epithelial cells. This interaction leads to disruption of intercellular structures such as tight junctions (TJ). We recently showed that the E. histolytica complex EhCPADH112, formed by the EhADH112 adhesin and the EhCP112 cysteine protease, participates during epithelial invasion. To elucidate the particular role of EhADH112 in this process, we overexpressed this adhesion molecule in MDCK epithelial cells. Expression of EhADH112 was proven by RT‐PCR and western blot assays. EhADH112 localized at the plasma membrane of epithelial cells, similar to its location in trophozoites. EhADH112 improved adhesion between epithelial cells induced by an increase in TER and expression of TJ proteins. Importantly, infection of MDCK cells expressing EhADH112 with trophozoites caused a faster drop in TER and more epithelial damage compared to control cells; suggesting that EHADH112 in epithelial cells serves as a ligand for the parasite, facilitating trophozoite entrance into the epithelium. Combined with our previous results that EhADH112 localizes to TJ after secretion by trophozoites, EhADH112 may be a promising new target to prevent amebiasis.Grant Funding Source: Supported by Institute of Science and Technology of the Federal District (64/2012)
Micromanaging inflammation and tissue repair (212.4)
Authors: Roy Sashwati 
Published: June 2021

Inflammation is a protective response of the body to infection or injury. Given that miRNAs are fundamental to the post‐transcriptional control of gene expression, it is not surprising that role of specific miRNAs in the immune and inflammatory response has been discovered. The best characterized miRNA for inflammation are miR‐146, miR‐21 and miR‐155, all of these have been shown to be strongly induced in multiple cell types by proinflammatory stimuli following tissue injury. At an injury‐site, efficient clearance of apoptotic cells by wound macrophages or efferocytosis is a pre‐requisite for the timely resolution of inflammation. Emerging evidence indicates that miR‐21 may regulate the inflammatory response. The significance and mechanisms of miR‐21 in the regulation of efferocytosis mediated suppression of innate immune response, a key process implicated in resolving inflammation following injury will be elucidated.Wound healing research in the author's laboratory is funded by NIDDK R01 DK076566 to SR.