bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent down‐regulation of Sep15 and TR1, but not deficiency in both genes, affects cancer phenotypes of mouse colon carcinoma cells
Authors: Tsuji Petra Akiko , Carlson Bradley A , Yoo Min-Hyuk , Xu Xue- Ming , Naranjo-Suarez Salvador , Davis Cindy D , Gladyshev Vadim N , Hatfield Dolph L
Published: June 2021

The cancer preventive properties of the essential nutrient selenium are partly mediated through selenoproteins. Herein, the effect of individual and combined down‐regulation of the 15 kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) in mouse colon carcinoma CT26 cells was examined. shRNA knockdown of either Sep15 or TR1 inhibited their anchorage‐dependent and ‐ independent cell growth, primary tumor growth and lung metastasis. Surprisingly, double knockdown of Sep15 and TR1 reversed the effects seen in single knockdowns. FACS analysis revealed that the significant G2/M cell cycle arrest in shSep15 cells was no longer observed in cells lacking both Sep15 and TR1. To investigate the molecular targets affected by single vs. double knockdown, gene expression was analyzed in control, Sep15‐, TR1‐ and Sep15/TR1‐knockdown CT26 cells using microarrays. Our analyses revealed that the expression of GBP‐1, the top upregulated gene in shSep15 cells, was not affected in shSep15/TR1 cells. The results suggest that the independent down‐regulation of either Sep15 or TR1, but not the double‐knockdown, resulted in changes of the cancer phenotype of mouse colon carcinoma cells. Funded by NCI Intramural support, the Cancer Prevention Fellowship Program, and NIH grants.
Bioactive compounds of dealcoholized fermented berry fruit beverages inhibit inflammation in vitro and are a good source of antioxidants
Authors: Johnson Michelle , de Mejia Elvira Gonzalez , Lila Mary Ann , Yousef Gad G
Published: June 2021

Berries are one of the best dietary sources of polyphenolic compounds and are associated with decreased markers of chronic inflammation linked with metabolic diseases. The objective was to evaluate bioactive compounds from dealcoholized blueberry‐blackberry fermented beverages in order to optimize blends based on in vitro inhibition of markers of inflammation and antioxidant capacity. Polyphenolic‐enriched fractions obtained from fermented beverages were analyzed. Main anthocyanins (ANCY) in blueberry and blackberry blended beverages, as identified by HPLC, were malvidin‐3‐glucoside and delphinidin‐3‐arabinoside. Total anthocyanins in enriched fractions ranged from 642 to 1550 mg/ml, cyanidin‐3‐glucoside (C3G) equivalents. Antioxidant capacity ranged from 5.2 ± 0.3 to 16.4 ± 1.8 and 6.2 ± 0.8 to 8.1 ± 1.0 mmol trolox equivalents (TE)/L for the ANCY‐ and proanthocyanidin (PAC)‐enriched fractions, respectively. None of the fractions were cytotoxic to macrophages at concentrations up to 100 μM C3G equivalents, the concentration used to measure markers of inflammation iNOS, COX‐2, PGE‐2, IL‐6, TNF‐α, and NF‐κB. The in vitro anti‐inflammatory activities were correlated with total anthocyanins and antioxidant capacity. These results suggest that bioactive compounds in highbush blueberry and blackberry fermented beverages are beneficial sources of antioxidants and inhibitors of inflammation.

Grant Funding Source: Office of Research, Dixon Springs Research Center
Ecklonia cava polyphenol prevents ethanol‐induced liver injury in rats
Authors: Kojima-Yuasa Akiko , Takahashi Mai , Tabuchi Masaki , Akahoshi Yasumitsu , Terada Masaki , Matsui-Yuasa Isao
Published: June 2021

Introduction

The development of alcoholic liver disease is a complex process involving both the parenchymal and non‐parenchymal cells in the liver. Here, we examined the effect of the extract of Ecklonia cava, a brown algae, on ethanol‐induced liver injury.

Methods

1) Isolated hepatocytes or hepatic stellate cells (HSCs) were cultured with or without 100 mM ethanol. The cells were cultured with Ecklonia cava polyphenol (ECP) (0~25 μg/ml) for 0~24 hrs. 2) Male Wistar rats were fed a diet with or without 0.02 or 0.2% ECP. Animals were given drinking 5% (v/v) ethanol with two doses of CCl4 (0.1 ml/kg BW, i.p.) weekly for 3 weeks.

Results

In cultured hepatocytes, the treatment of ECP suppressed ethanol‐induced increase in cell death via the protecting the levels of intracellular glutathione (GSH). In HSCs, the treatment with ECP suppressed ethanol‐induced increase in expression of type I collagen and α‐SMA via the remaining the levels of intracellular ROS and GSH. It has been reported that hepatic histological changes in ethanol‐CCl4 induced fibrosis model were similar to those found in human alcoholic cirrhosis. Therefore, we examined the effect of ECP on serum AST and ALT activities and liver fibrosis in rats treated with ethanol plus CCl4. The treatment of ECP suppressed the leakage of AST and ALT in the ethanol plus CCl4 treated rats. The collagen accumulation in the liver and hepatic necrosis was observed in ethanol plus CCl4 treated rats, but ECP treatment totally protected against ethanol plus CCl4 induced liver fibrosis and necrosis.

Conclusion

These results suggest that ECP may be a candidate for preventing ethanol‐induced liver injury.
Increased adiposity induced by high dietary butter oil increases vertebrae trabecular structural indices in rats
Authors: Nielsen Forrest Harold
Published: June 2021

Obesity has been associated with both improved and impaired bone health, and other dietary factors apparently affect the nature of the association. An experiment was performed to determine whether increased adiposity induced by high dietary butter oil impairs bone structure and whether that effect is exacerbated by moderate magnesium (Mg) deficiency. Groups of 24–25 male Sprague‐Dawley rats aged 6 wk were fed dietary Mg at 250, 500, or 750 mg/kg and dietary fat at 10% (4.4% butter oil, 5.6% soybean oil) or 45% (39.6% butter oil, 5.4% soybean oil) of total energy. After 24 wk, 12 rats from each group fed high dietary butter oil exhibited increased % and g fat (determined by MRI) and g epididymal fat. Decreased plasma 1, 25‐(OH)2‐vitamin D and parathyroid hormone and bone magnesium indicated the rats fed the low‐Mg/diet were Mg‐deficient. Vertebrae trabecular amount, number, thickness, and connectivity were increased by the high butter oil feeding. Moderate Mg deficiency did not affect vertebrae micro architecture. Moderate Mg deficiency decreased femur strength (force to break), which effect, was alleviated by high dietary butter oil. Findings suggest that a rat with increased adiposity caused by high dietary butter oil is not a suitable model for the determination of whether Mg deficiency modifies impaired bone health associated with obesity.
Sow milk, formula and combined feeding differentially regulate gene expression in piglet colon
Authors: Radlowski Emily C , Wang Mei , Monaco Marcia H , Drnevich Jenny , Donovan Sharon M
Published: June 2021

Breastfeeding is recommended for the first year of life. However, breastfeeding rates in the U.S. decline from 77% at birth to 43% by 6 months and only 13% of these infants are exclusively breastfed, while the remainder are supplemented with formula (combined feeding; CF). Herein, we developed a novel piglet model to investigate the effect of CF on the colonic transcriptome. Newborn piglets were randomized into 3 groups: sow‐reared (SR), formula fed (FF) and CF (n=6 per group). SR remained with the sow 24h/day and FF were fed a sow milk replacer. CF piglets were sow‐reared for 5d and were then rotated between the sow and formula feeding every 12h. On d21, ascending colon was collected and mRNA was extracted. Gene expression was assessed using a porcine microarray (Agilent). Among 25,273 probes, 449 were differentially expressed (FDR p<0.2). Bioinformatic analyses using MetaCore, revealed that the most significant GeneGo pathway maps were oxidative phosphorylation, apoptosis, immune response, lipid metabolism and cholesterol biosynthesis. On‐going analyses are investigating relationships between host gene expression and composition of the colonic microbiota. (BMS Freedom to Discover Award)
The role of miR‐17‐92 cluster in hepatic carcinogenesis
Authors: Zhu Hanqing , Han Chang , Wu Tong
Published: June 2021

MiR‐17‐92 cluster is a potent oncogenic miRNA which has been shown to promote cell proliferation, increase angiogenesis and sustain cell survival in several cancer types. However, the potential role of miR‐17‐92 cluster in hepatic carcinogenesis has not been investigated. This study was designed to examine the impact of miR‐17‐92 in hepatic cancer cells. qRT‐PCR analysis showed that the expression of miR‐17‐92 cluster is increased in several human hepatic cancer cell lines (Hep3B, Huh7 and HepG2) compared to the transformed, non‐cancerous hepatic cell line, THLE‐2. The miR‐17‐92 inhibitors (blocking the entire cluster or individual miRNAs within the cluster) prevented hepatic cancer cell growth. In contrast, stable transfection of pri‐miR‐17‐92 cluster increased tumor cell proliferation. Western blot analysis showed decreased PTEN protein in hepatic cancer cells transfected with the pri‐miR‐17‐92 cluster, suggesting that PTEN may represent one of the miR‐17‐92 downstream targets. Experiments are ongoing to document hepatocellular cancer development in transgenic mice with targeted expression of homo miR‐17‐92 cluster gene in the liver (driven by albumin‐cre, with or without diethylnitrosamine treatment). Results of these experiments are expected to provide important in vitro and in vivo evidences to define the role of miR‐17‐92 in hepatic carcinogenesis and tumor progression.
IFNg influences epithelial proliferation by modulating Aktbeta catenin signaling downstream of cadherins.
Authors: Dominguez Porfirio Nava , Kolegraff Keli N. , Koch Stefan , Parkos Charles , Nusrat Asma
Published: June 2021

Intestinal mucosal inflammation in inflammatory bowel disease (IBD) is associated with perturbed intestinal epithelial homeostasis (proliferation/differentiation) and barrier function that are mediated, in part, by pro‐inflammatory cytokines such as IFNγ. However, the mechanisms governing IFNγ‐mediated regulation of epithelial homeostasis (proliferation/differentiation) and barrier function are not understood. Since a master regulator of epithelial homeostasis is E‐cadherin we investigated if IFNγ modulates epithelial homeostasis by regulating signaling proteins downstream of intestinal epithelial cadherins that also regulate cell proliferation. Using complementary in vitro and in vivo approaches, we identified protein kinase B (PKB/Akt) as a key protein that regulates stability of b‐catenin down‐stream of Ecadherin. IFNγ but not TNFα was observed to initially promote phosphorylation and activation of Akt and β‐catenin resulting in a burst of cell proliferation. However, sustained exposure to IFNγ induced stabilization of E‐cadherin and β‐catenin that was dependent on the cytoplasmic scaffold protein, 14‐3‐3ζ and Akt resulted in inhibition of β‐catenin induced cell proliferation. These results provide a novel paradigm through which sustained exposure to IFNγ results in inhibition β‐catenin signaling, reduced cell proliferation and barrier function in IBD.

This work was supported by CCFA Fellowship and AGA Research Scholar Awards (PN) and NIH grants DK61379 (CP), DK55679 and DK59888 (AN).
Lipocalin 2 confers protection against endotoxin‐induced sepsis in mice
Authors: Vijay-Kumar Matam , Aitken Jesse D , Srinivasan Gayathri , Zhang Benyue , Gewirtz Andrew T
Published: June 2021

Sepsis is characterized by elevated systemic proinflammatory cytokines and agents that can act as amplifiers (HMGB1) or dampeners (sIL‐1Ra) of inflammation and thus play a decisive role in sepsis. Lipocalin 2 (Lcn2), which is upregulated by log orders of magnitude during inflammation but its role in sepsis, is largely unknown. Lcn2 deficient mice (Lcn2KO) and their WT littermates were given E. coli LPS (20mg/kg BW) i.p. and monitored for mortality. Serum TNFα, IL‐18 and aminotransferases were analyzed. Splenocyte apoptosis was assayed 24h after LPS by TUNEL staining, caspase 3 and flow cytometry. Peritoneal cells from WT and Lcn2KO mice were stimulated with LPS and cytokines, COX2 and iNOS were analyzed. In WT mice, LPS‐induced systemic Lcn2 peaked at 24h and returned to basal levels by 48h. All Lcn2KO died by day 8 while only 20% mortality was observed in WT mice. In addition, Lcn2KO exhibited substantial elevation of every parameter tested including both pro and anti‐inflammatory cytokines. Further, splenocytes exhibited extensive apoptosis as measured by caspase 3 and TUNEL staining. Flow cytometry revealed that apoptosis of neutrophils, CD3+CD4+ and dendritic cells were significantly increased in Lcn2KO. Our data demonstrate that Lcn2 is a host protective factor during sepsis and, given its multifunctionality, small size, and simple structure it may be developed as potential therapeutic agent to treat sepsis.
Immune modulation by prolyl hydroxylase inhibition contributes to the prevention of endotoxemia in a murine model of inflammatory bowel disease.
Authors: Keely Simon , Baird Alan , Kominsky Douglas , McNamee Eoin N , Hansbro Philip M , Shalwitz Robert A. , Colgan Sean P
Published: June 2021

Hypoxia‐inducible factor (HIF) prolyl hydroxylation inhibition (PHDi) has been shown to reduce mucosal disease severity in murine models of colitis at several levels of clinical and biochemical scoring. However, little is known about PHDi influence on systemic immune function during mucosal inflammation. Induction of TNBS colitis leads to an early pyrogenic response (fever), followed by a cryogenic response (hypothermia) due to bacteremia. We hypothesized that PHDi modulates systemic immune responses to bacteremia, associated with colitis. TNBS colitis mice, were treated with AKB‐4924, a HIF‐1 isoform‐predominant PHD inhibitor. AKB‐4924 treatment led to significantly reduced weight loss and disease activity, compared to vehicle. AKB‐4924 groups were pyrogenic, but did not become cryogenic. AKB‐4924 augmented epithelial barrier function and led to a 50‐fold reduction in serum endotoxin during colitis. AKB‐4924 modulated cytokines involved in pyrogenesis and cryogenesis, significantly reducing serum levels of IL‐1β (2‐fold), IL‐6 (17‐fold) and TNF‐α (3‐fold), while increasing IL‐10 (2‐fold). Neutrophils exhibited increased phagocytotic capacity and reduced TNF‐α expression (2‐fold) with AKB‐4924 pretreatment. Together, these results suggest that AKB‐4924 may prevent TNBS colitis induced endotoxemia on a multifactorial level, through previously unappreciated systemic mechanisms.
Eating identity and perceptions of the neighborhood food environment
Authors: Blake Christine E , Barnes Timothy L , Nichols Michele D , Liese Angela D
Published: June 2021

We have previously shown that perceptions of the food environment (PFE) do not always correspond to actual environments. Perceptions are likely influenced by psychosocial factors, including eating identity (EI), conceptualized here as affinity for four dimensions: healthy, meat, picky, and emotional eating. The purpose of this study was to examine associations of EI dimensions with PFE. We used data from a telephone survey of adults in South Carolina, part of a larger study on PFE. 851 participants completed the EI and PFE questions. General linear models, adjusted for age, race, gender, and food access were used to assess EI and PFE relationships. High healthy EI scores were positively associated with perception of healthfulness of their environment (β=.14;p<.01) and negatively with fast food opportunities (β= −.05;p<.01). The same directions of associations was observed for picky EI scores (β=.19;p<.01, β= −.10;p<.0001, respectively). Emotional EI scores were negatively associated with perception of problematic access to food shopping (β= −.03;p<.05). Meat EI scores were not significantly associated with perceptions. Individuals reporting greater affinity for different EI dimensions perceive aspects of similar food environments differently. Understanding how EI influences perceptions of food environments may be useful in etiological and intervention research. Funded by NCI R21CA132133‐02S1.
Potential Therapies with Adult Stem/Progenitor Cells from Bone Marrow (MSCs) and the Proteins They Produce in Response to Injuries from Injured Tissues
Authors: Prockop Darwin J
Published: June 2021

Therapeutic benefits in a number of models for human disease have been reported with administration of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or mesenchymal stromal cells (MSCs). We observed that intravenously administered MSCs improved myocardial infarction in mice by being trapped in lung where they created microemboli that activated the cells to synthesize TSG‐6, and the TSG‐6 reduced the excessive inflammatory response that damaged cardiomyocytes (Lee et al. Cell Stem Cell 2009). We also observed that intraocular administration of TSG‐6 reduced the excessive inflammatory response that damaged the cornea in a rodent model for chemical injury of the eye (Oh et al. PNAS 2010). In parallel experiments we observed that retinal degeneration was decreased in a rat model for retinitis pigmentosa by intravitreal administration of STC‐1 (Roddy et al. ARVO abstract, 2011), an anti‐apoptotic protein produced by hMSCs in response to signals from apoptotic cells (Block et al. Stem Cells 2009). The results indicate that some but not all the therapeutic benefits observed with administration of MSCs in disease models can be explained by the cells being activated to express either TSG‐6 or STC‐1.

Supported in part by NIH grants HL 073755, PO1 RR 17447, and 1R21EY020962
microRNA regulation of cardiac cell fate, morphogenesis and function
Authors: Srivastava Deepak
Published: June 2021

Gradients of signaling and transcription factors result in distinct cellular responses during organ formation and maintenance suggesting that the precise dose of major regulatory proteins must be tightly controlled. Studies in our lab of multiple cardiac‐enriched miRNAs reveal that they coordinate decisions of cellular proliferation, differentiation and response to stress via intricate transcriptional and translational networks. We have identified individual miRNAs that govern differentiation and development of embryonic stem cell (ESC)‐ and induced pluripotent stem cell (iPSC)‐derived multipotent cardiac progenitors into cardiomyocytes, endothelial and smooth muscle cells. In each case, specific miRNAs directly regulate the activity of pivotal transcriptional and signaling networks, often with positive and negative feedback regulation. The effects of miRNAs on numerous physiologic outcomes are achieved by coordinated regulation of multiple mRNA targets that function in common pathways. As a result, manipulation of miRNAs holds potential in influencing the outcome of cell fates and cellular homeostasis, particular in the cardiovascular system.
Role of an integrin‐interacting protein in the control of EMT in cancer and fibrosis
Authors: Zhang Hongquan
Published: June 2021

Integrins are transmembrane proteins that link extracellular matrices with cytoskeleton and mediate a variety of biological functions including cell adhesion and migration as well as tumor cell invasion and metastasis. In this report, we identified a novel role of an integrin‐interacting protein Kind‐2 in the control tumor metastasis in human breast carcinoma via activation of canonical Wnt/TCF pathway. An array based systematic analyses indicated an overall initiation of tumor invasion and metastasis program including upregulation of key Wnt/TCF signaling targets TCF4, LEF1 and HOXB9 as well as epithelial‐mesenchymal transition (EMT) regulatory transcriptional factors Snail, Slug, Twist and Zeb1. The Kind‐2/beta‐catenin signaling greatly accelerates tumor cell proliferation, migration, and invasion in vitro, and promotes tumor growth and lung‐metastasis in mice, demonstrating a role of Kind‐2 in cancer progression. On the other hand, we also indentified that Kind‐2 is involved in the regulation of TGF‐β signaling and promotes renal interstitial fibrosis by inducing EMT. Depletion of Kind‐2 in kidney reduces renal interstitial fibrosis in UUO mice including reduced collagen deposition and decreased α‐SMA and fibronectin expressions. Overall, our results indicate an important role of Kind‐2 in the regulation of tumor metastasis and kidney fibrosis via an EMT program.
Effectiveness, Adaptation, and Health Risks of Embalming Fluids: Just what is the Solution?
Authors: Sparey Kate
Published: June 2021

The use of embalming fluids to preserve tissues, organs, and whole cadavers has changed significantly over thousands of years. From mummification in ancient Egypt, Da Vinci's use of wax injection, through to modern day use of formaldehyde and subsequent adaptations. The process of tissue preservation and the technology behind formulation of embalming fluids is important from both an efficacy and health perspective.

Formaldehyde remains the current fixative of choice in embalming solutions due to its ability to remove the food source for tissue degrading bacteria by permanently denaturing cellular proteins. This ensures long term survival of the tissue for use in teaching Anatomy, but there are some limitations in using this method; most notably flexibility of the tissue. Specimens become heavy and unwieldy, and do not accurately convey some of the movements, tensions, and strengths of certain tissues in vivo. There are also certain health risks to formaldehyde use, particularly relating to skin contact, inhalation and its potential carcinogenic effects. Alternative embalming solutions currently in use and adaptations being developed in order to improve on this technology will be discussed.
The CRISPR‐Cas system: small RNA‐guided invader silencing in prokaryotes
Authors: Terns Becky , Hale Caryn , Carte Jason , Elmore Joshua , Majumdar Sonali , Glover Claiborne V.C. , Graveley Brenton , Terns Michael
Published: June 2021

CRISPR‐Cas systems are recently discovered, RNA‐based immune systems that control invasions of viruses and plasmids in archaea and bacteria. Prokaryotes with CRISPR‐Cas immune systems capture short invader sequences within the CRISPR loci in their genomes, and produce small RNAs from the CRISPR loci (crRNAs) that recognize the invading nucleic acids and guide Cas proteins to degrade (or otherwise silence) the invader. There are multiple variations of the pathway mediated by distinct components and mechanisms that we are now delineating.

Pyrococcus furiosus has 3 CRISPR‐Cas systems populated by 27 Cas proteins and 200 crRNAs. We have found that CRISPR transcripts are “diced” into individual invader‐targeting crRNAs by Cas6, a sequence‐specific riboendonuclease. The mature crRNAs contain a signature sequence element that is important for function. The CRISPR‐Cas systems in P. furiosus target invaders at both the RNA and DNA level. We have identified 3 distinct potential crRNA‐Cas protein effector complexes (arising from the 3 systems), and have determined that one, the Cmr complex, cleaves complementary RNAs at fixed intervals along the region of complementarity between the crRNA and target RNA. We have also initiated efforts to direct Cmr complexes to cleave novel target RNAs (a la prokaryotic RNAi).

This work was supported by NIH grant RO1GM54682 (including ARRA funds) to B.T. and M.T.
Differential regulation of pancreas digestive enzymes during the development of diet‐induced‐obesity of C57BL/6J mice
Authors: Birk Ruth Z , Rubio-Aliaga Isabel , Boekschoten Mark V , Müller Michael , Daniel Hannelore
Published: June 2021

Background

Pancreatic enzymes are essential for digestion of dietary components and regulated by them. Dietary high fat (HF) consumption is a contributing factor in diet‐induced‐obesity (DIO) and requires pancreas adaptation.

Objectives

Investigating the effects of chronic HF diet on pancreatic digestive enzymes transcripts in DIO C57BL/6J mice.

Methodology

Mice were fed diets containing 10% or 45% of energy derived from fat for 12 weeks (10 mice/group). Pancreas digestive enzymes transcripts were analyzed (0, 4 and 12 weeks) using quantitative RT‐PCR.

Results

C57BL/6J mice fed HF diet developed obesity, hyperleptinemia, hyperglycemia and hyperinsulinemia. Pancreatic Lipase, Pancreatic Lipase Related Protein‐2 and Pancreatic PhospholipaseA2 transcripts were initially elevated; however, they were down‐regulated to basal control levels at 12 weeks. Amylase transcripts increased in response to higher dietary carbohydrate content. Proteases transcripts did not change. Elastase1 transcripts increased on the HF diet.

Conclusion

DIO C57BL/6J mice down‐regulate expression of specific lipases. This suggests a regulatory mechanism to reduce fat digestion, absorption and storage.

Study funded partly by NuGO
The effect of tomato powder, soy germ, or a combination on prostate carcinogenesis in TRAMP mice
Authors: Zuniga Krystle , Clinton Steven , Thomas-Ahner Jennifer M. , Erdman John W.
Published: June 2021

Epidemiological and laboratory studies support the hypothesis that diets rich in soy or tomato food products may reduce the risk of prostate cancer (PCa). The objective of this study was to investigate the in vivo effect of diets containing tomato powder, soy germ, both, or neither, on the progression of PCa in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Four‐week old male TRAMP mice (n=118) were randomized to consume experimental diets: AIN‐93G control, 10% tomato powder (TP), 2% soy germ (SG), or 10% tomato powder + 2% soy germ (TP+SG) until 18 weeks of age. Body weight and food intake were similar. The prostate‐seminal vesicle (P‐SV) complex weights among each of the three dietary intervention groups were non‐significantly reduced compared to the control group. Prostate pathology shows a range of PIN to invasive carcinoma, with grading and staging underway. Our results with P‐SV weights suggest that dietary interventions with tomato or soy may reduce TRAMP cancer burden.

Grant Funding Source: NIH under Ruth L. Kirschstein National Research Service Award (1 F31 CA153804‐01A1)
Empty calories consumption in Brazil: an analysis of the Brazilian National Dietary Survey 2008–2009
Authors: Pereira Rosangela Alves , Miles Donna R , Sichieri Rosely , Popkin Barry M
Published: June 2021

Empty calories intake has not been studied in Brazil, where the first nationally representative dietary survey of individuals ten years and older (n=34,003) with detailed food records revised by direct interview was collected in 2008–2009. Sources of excessive saturated fat and sugar were identified based on dietary recommendations (a maximum of 7% of energy coming from saturated fat and a maximum of 10% of energy coming from sugar), beverages energy density (>20 kcal/100ml) and sugar content of milk/soy/yogurt beverages (>6g/100ml). About 25% of energy intake in Brazil comes from empty calories. Overall, higher intake of empty calories was found among women, adolescents, higher educated and higher income individuals as well as those living in the Southern Region. Sugar sweetened beverages, the most consumed empty calorie food, provided about 13% of total caloric intake. Sweets and desserts, sandwiches and burgers, alcoholic beverages, pasta, and pizzas also provided major levels of energy intake. The high levels of empty calories consumption poses important health concerns for the Brazilian population. Financial support: Brazilian National Council for Scientific and Technological Development (CNPq).
Dietary supplement use during pregnancy: results from the National Health and Nutritional Examination Survey (NHANES)
Authors: Branum Amy , Singer Barbara , Bailey Regan
Published: June 2021

In the United States, women of child‐bearing age are advised to take a multivitamin dietary supplement before and during pregnancy to reduce the risks of some birth defects and enhance nutritional status. Despite these recommendations, dietary supplement use among pregnant women in the US has not been described using nationally representative data. Our objective was to examine the prevalence of and characteristics associated with dietary supplement use among pregnant women using NHANES 1999–2006 (n=1,350). Of pregnant women, 78% (Standard Error (SE): 2.1) reported supplement use in the month prior to the interview. Among pregnant women those reporting supplement use were more likely to be 30 years or older (41%, p<0.0001), have at least some college education (66%, p<0.0001)), be non‐ Hispanic White (63%, p<0.0001), married (67%, p<0.0001), and be in their second (41%, p<0.01) or third (40%, p<0.01) trimesters compared to those who reported no supplement use. After adjusting for all other characteristics, women with at least some college education remained more than 3 times more likely to use supplements during their pregnancy as compared to those with less than a high school education (Adjusted Odds Ratio (AOR) = 3.3, 95% CI 1.6, 6.8). ). Additionally, multiparous women were less likely to use supplements than primiparous women (AOR = 0.4, 95% CI 0.2, 0.9). These findings add to the relatively few studies describing supplement use by pregnant women in the US and identify characteristics that potentially could be useful for targeted prenatal nutritional intervention.
Arterial Stiffness and Blood Pressure are Reduced After Watermelon Supplementation in Obese With Prehypertension and Hypertension
Authors: Figueroa Arturo , Sanchez-Gonzalez Marcos Angel , Wong Alexei , Arjmandi Bahram H
Published: June 2021

Objective

To examine the effects of watermelon supplementation on arterial stiffness (brachial‐ankle pulse wave velocity, baPWV) and aortic blood pressure (BP) in obese adults.

Methods

Fifteen middle‐aged (58±1 y) obese individuals (BMI: 37.3±1.8 kg/m2) with high BP (151±4 mmHg) were randomly assigned to receive watermelon powder containing 6 g daily of L‐citrulline/L‐arginine or placebo powder (PL) in a 6‐week cross‐over study with a 2‐week washout period. Subjects were evaluated before and after the interventions to assess changes in baPWV, BP, aortic augmentation index (aAIx), and plasma angiotensin II levels.

Results

baPWV (−1.3±0.3 m/s), brachial systolic BP (SBP, −13±3 mmHg), brachial diastolic BP (DBP, −7±1 mmHg), aortic SBP (− 9±3 mmHg), aortic DBP (−7±1 mmHg), and angiotensin II (−10±2 pg/ml) significantly (p<0.01) decreased after watermelon compared with PL. Although aAIx was not affected, wave reflection amplitude decreased (−9±3 mmHg, p<0.01) after watermelon compared with PL.

Conclusion

Watermelon supplementation caused a marked decrease in arterial stiffness, peripheral BP, and aortic BP in obese individuals with prehypertension and hypertension. Our findings suggest that watermelon supplementation may improve arterial function through attenuation of the vascular effects of angiotensin II and improved wave reflection amplitude.
Hypolipidemic effect of a blue‐green alga, Nostoc commune var. Sphaeroides Kützing, is attributed to algal residue but not lipid extract in C57BL/6J mice
Authors: Ku Chai Siah , Kim Bohkyung , Pham Tho X. , Yang Yue , Park Youngki , Carr Timothy , Weller Curtis , Lee Jiyoung
Published: June 2021

We previously reported a hypolipidemic effect of an edible blue‐green alga (BGA), Nostoc commune var. Sphaeroides Kützing (NO) in mice. To further evaluate whether the lipid‐lowering effect of NO is attributable to algal residue or lipid extract (LE), male C57BL/6J mice were fed an AIN‐93M diet supplemented with 2.5% and 5% by wt of whole algae or LE equivalent amount present in 5% whole algae for 4 wk. Spirulina Platensis (SP), the most common BGA for human consumption, was also tested for comparison. Plasma total cholesterol and triglyceride were significantly lowered in whole NO‐fed animals but not in NO LE and SP groups. Hepatic total cholesterol and triglyceride levels were not significantly different between groups but free cholesterol was higher in NO 2.5% and all SP‐fed groups. Expression of hepatic genes for cholesterol metabolism, such as HMG CoA reductase and sterol regulatory element binding protein‐2, was significantly increased in 5% NO group. Lipogenic gene expression in the liver was not altered in all groups whereas carnitine palmitoyl transferase I and acyl‐CoA oxidase mRNA levels were induced in 5% NO group. Significant reduction in intestinal cholesterol absorption was also observed in whole NO groups. In conclusion, NO algal residue contains bioactive components that inhibit intestinal cholesterol absorption and consequently exert a hypolipidemic effect in mice.

Grant Funding Source: NIH R21AT005152
Associations between common variants in CYP24A1 and risk of obesity in Chinese Hans
Authors: Lu Ling , Gan Wei , Zhu Jingwen , Tang Haiying , Li Huaixing , Lin Xu
Published: June 2021

Poor vitamin D status could lead to obesity in Human and gene variants may modify vitamin D metabolism. We aimed to investigate associations of variants in CYP24A1, encoding 24‐hydroxylase, an enzyme involved in vitamin D degradation, with obesity and its related phenotypes in Chinese Han. Eight tag single‐nucleotide polymorphisms (SNPs) in CYP24A1 (rs2245153, rs927651, rs3787554, rs2181874, rs2762941, rs3886163, rs2248461 and rs2296241) were genotyped in a population‐based sample including 474 obese (BMI ≥28kg/m2), 1221 overweight (24 ≤BMI <28kg/m2) and 1515 normal‐weight subjects (BMI <24kg/m2). After adjustment for age, sex, residential region, season of blood collection and physical activity, five SNPs (rs3787554, rs2181874, rs2762941, rs3886163 and rs2296241) showed significant associations with BMI, waist circumference and/or risks of overweight and obesity (P ≤0.04). After Bonferroni corrections, the associations of rs3886163 A‐allele (OR = 1.17, P=0.0060) and rs2762941 A‐allele (OR = 1.20, P = 0.0017) with risk of overweight remained significant (P <0.0063, 0.05/8 tests). In conclusion, the variants in CYP24A1 might contribute to risks of obesity and related traits in Chinese Hans. This work was supported by the research grants 2009KIP401, 2011CB504002, KSCX2‐EW‐R‐10, 2009AA022704 and CRC2010008.
Vitamin D and TNF‐alpha effects on adipogenesis and inflammation in human adipocytes
Authors: Wood Richard James , Gray Brianna E , Kim Young-Cheul , Ronnenberg Alayne G
Published: June 2021

Obesity is associated with meta‐inflammation, a chronic low‐grade inflammatory state with elevated adipose pro‐inflammatory cytokine expression. Elevated TNF‐alpha is a mediator of obesity‐associated insulin resistance. Low vitamin D status is common in obese people, but its inflammatory role in adipocytes is unknown. Our study objective was to determine the effect of 1,25(OH)2D on TNF‐alpha induced changes in adipogenesis and pro‐inflammatory cytokine expression in human primary adipocytes in culture. We differentiated human primary adipocytes in the presence or absence of 1,25(OH)2D and TNF‐alpha and measured lipid accumulation and mRNA expression. We found no effect of 1,25(OH)2D on adipogenesis or proadipogenic gene expression, despite a clear induction of the vitamin D‐responsive gene CYP24 (24‐hydroxylase). Marked inter‐individual differences in 1,25(OH)2D effects on MCP‐1 expression were observed. TNF‐alpha blocked adipogenesis and expression of PPAR‐gamma and C/EBP‐alpha and increased expression of pro‐inflammatory genes IL‐6 and MCP‐1, but not IL‐8. We found no evidence of an interaction between TNF‐alpha and 1,25(OH)2D on adipogenesis or pro‐inflammatory cytokine gene expression. The factors responsible for differential inter‐individual responses of adipocytes to 1,25(OH)2D warrant additional study. Funding source: HATCH MAS00992
Effects of diet macronutrient composition on visceral adiposity during weight maintenance
Authors: Miskimon Amy Kathleen , Goree Laura Lee , Ellis Amy C , Chandler-Laney Paula , Casazza Krista , Lockhart Mark , Gower Barbara
Published: June 2021

Macronutrient composition of the diet may affect propensity to distribute fat centripetally, and thus influence risk of cardiovascular disease and type 2 diabetes. The objective of this study was to determine if consumption of a relatively low glycemic load (GL) diet would result in preferential loss of visceral adipose tissue under eucaloric conditions and to determine if these effects were gender‐specific. Participants were 69 healthy overweight men and women. Body composition was assessed by DXA and fat distribution by CT scan at baseline and after 8 weeks of a eucaloric diet intervention. Participants were provided all food for the intervention period, and randomized to either a low GL diet (<45 points per 1000 kcal; n=40) or high GL diet (>75 points per 1000 kcal, n=29). Results indicated women in the low GL group lost 15.1% (P=0.001) IAAT, while women in the high GL diet group lost 1% (P=0.82), men in the high GL diet group gained 4.2% (P=0.55), and men in the low GL diet group lost 4.3% (P=0.44). Women on the low GL diet had a significant reduction in SHBG (p=0.01) after 8 wks and loss of IAAT was significantly associated with 8‐wk estradiol (p=0.02). Consumption of a relatively low GL diet may induce reduction in IAAT independent of weight change, specifically among women. These affects may be mediated by diet‐induced alterations in the sex hormone environment.
What influences the sustainability of community‐based child nutrition programs in the Peruvian highlands?
Authors: Kim Sunny S , Creed-Kanashiro Hilary , Bartolini Rosario , Constas Mark A , Habicht Jean-Pierre , Stoltzfus Rebecca J
Published: June 2021

Long‐term viability of health and nutrition programs is a desired goal of donors and program implementers, yet little evidence exists on how to influence sustainability in developing countries. We previously assessed sustainability of 2 community‐based child nutrition programs (ADRA and CARE) in Peru, 2 yrs after project termination, and found few activities were sustained. With 94 interviews with program delivery actors and 22 focus groups with mothers in 21 communities of the 2 programs, we used pattern matching to test theoretical propositions (related to the initial program, local organizations, and community) against observed patterns of factors associated with sustainability. Forms and types of influential factors on sustainability reflected the forms and types of sustained activities, with common factors between programs. We found 3 factors of the initial program (broader community participation, positive perception of impact, and intentional actions at exit); 6 organizational factors (integration, external coordination, higher skills and training, positive perceived value of work, strong work motivation, and champions for child nutrition); and 4 community factors (perception of problem, integration, valuing of child nutrition, and champions). Addressing the contextual factors in program design and implementation is needed to achieve sustainability. Funders: NIH and Cornell University.

Grant Funding Source : NIH and Cornell University
Developing a food policy council through community‐based participatory research
Authors: Fitzgerald Nurgul , Finston Lisanne , Morgan Kathleen , Hallman William
Published: June 2021

Environmental factors and policies influence dietary intake patterns. This study aimed to establish a food policy council (FPC) through community‐based participatory research (CBPR) to influence food‐related policies and alleviate food insecurity. CBPR approach was used to build on the strengths of the community, develop partnerships, obtain funding, and establish a food policy council. Formative planning phase included 7 semi‐structured expert interviews and 3 community forums which were designed to inform the stakeholders, stimulate interest, integrate community's knowledge and priorities, and serve as co‐learning processes. These processes were used to develop the structure of the FPC, a community information toolkit, and initial focus areas for the FPC's strategic planning regarding the food system and policy recommendations. These focus areas included access to healthier foods, food‐related job creation, food safety nets, school food environments, and nutrition education. CBPR approach was incorporated into the structure of the FPC to support the sustainability of the initiative. This project indicated that CBPR was a feasible method to successfully develop a FPC that focuses on food systems and policy changes to support a healthier food environment.

Funded by the USDA Hunger‐free Communities Initiative.
Carotenoids and lipid peroxidation in human brains with and without Alzheimer's disease
Authors: Roe Annie J. , Scott Tammy M. , Chen Chung-Yen O. , Vishwanathan Rohini , Eggert Emily M.R. , Schalch Wolfgang , Wittwer Jonas , Johnson Elizabeth J.
Published: June 2021

Background

Oxidative stress may be involved in the development and progression of Alzheimer's disease (AD). Carotenoids are lipophilic antioxidants found in human brain, and may protect against lipid peroxidation.

Objective

To determine carotenoid concentrations and the magnitude of lipid peroxidation in brain tissue of decedents with and without AD.

Methods

Carotenoids in brain tissue were analyzed by HPLC. Lipid peroxidation was assessed by determining malondialdehyde (MDA) using a HPLC method. Data were expressed by wet weight. Carotenoid and MDA concentrations were log transformed to obtain normal distributions, and concentrations were compared between age‐ and sex‐matched AD (n=15) and non‐demented (n=15) groups using a Student's t‐test. Pearson's correlations were used to assess the relationship between MDA and carotenoid levels.

Results

Lutein, zeaxanthin, and lycopene concentrations were not different between groups. Cryptoxanthin and beta‐carotene concentrations were higher in the AD brains (p <0.01). There was no significant difference in MDA between groups or correlation with carotenoid concentrations within either group.

Conclusions

Elevated concentrations of cryptoxanthin and beta‐carotene in AD brains suggest that carotenoids may play a role in this disease. This pilot study was limited by the sample size, but demonstrates the feasibility of exploring these relationships in a larger study.

Support: USDA#51000‐073‐02S; DSM Nutritionals
The relationship between retinal carotenoids and cognitive function in healthy and cognitively impaired elders
Authors: Renzi Lisa M. , Dengler Melissa , Thorne Sarah Anna , Puente Antonio Nicolas , Hammond Billy R. , Miller L. Stephen
Published: June 2021

Lutein (L) and zeaxanthin (Z) are incorporated into the neural retina as macular pigment (MP), which is a biomarker of L+Z distributed throughout the cortex. Cortical L+Z may have the ability to improve cognitive function. The purpose of this study was to determine whether or not MP relates to cognition in healthy elders and elders with mild cognitive impairment (MCI). 41 elders (M = 75.5 ± 6.3 years) participated. 15 of the 41 elders met criteria for MCI. MP density was measured psychophysically, and cognition was assessed via the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Visual processing speed was also measured. MP density was related to cognitive function in the visuospatial (r = 0.43, p < 0.05) and attentional (r = 0.47, p < 0.05) domains of the RBANS in elders with MCI, but not in unimpaired elders. Elders with MCI were also less sensitive to flicker. These results suggest that MP's relationship to cognition varies with cognitive impairment.
Elevated dairy fat intake by lactating women increases milk fat and alters fatty acid profile, but does not change gene expression in the milk fat globule transcriptome
Authors: Hunt Katherine M , Brooker Sarah L , Williams Janet E , McGuire Michelle K , McGuire Mark A
Published: June 2021

Previous work has demonstrated that increased intake of dairy fat by lactating women increases milk fat percent and alters milk fatty acid profile. To investigate the effects of dairy fat consumption on cellular function in the mammary gland, we provided 15 lactating women with diets rich in full‐fat or non‐fat dairy products for 14 d in a randomized, crossover design. Milk fat was reduced when women consumed the non‐fat dairy diet compared to when they consumed the full‐fat dairy diet (2.41 ± 0.31 vs. 3.35 ± 0.28%, mean ± SEM, P < 0.05); concentrations of over 20 fatty acids also differed. Microarray analysis of gene expression in the milk‐fat globule transcriptome performed on samples from 6 of the subjects demonstrated only minor changes. Subsequent rt‐PCR validation of potential genes of interest revealed no alterations in gene expression. These data suggest that, despite treatment effects on milk fat percent and fatty acid profile, alterations in gene expression in the lactating mammary gland as a result of increased dietary dairy fat intake are minimal. Funded by the United Dairymen of Idaho.

Grant Funding Source : United Dairymen of Idaho
Commensal microbiota modulate ROS‐dependent cytoprotective gene expression in Drosophila intestinal epithelia
Authors: Mercante Jeffrey , Jones Rheinallt M , Gates Cymone , Luo Liping , Moberg Kenneth , Neish Andrew S
Published: June 2021

A growing body of data has emerged showing that gut commensal bacteria are essential for normal mucosal physiology and reparative function. However, the molecular bases for these symbiotic processes are not well understood. In this study we describe a novel role for gut commensal microbiota in protecting against xenobiotic insult. Compared to germ‐free flies, conventional (raised with normal microbiota) and conventionalized (colonized with known commensals) Drosophila are protected from gut‐directed injury. After conventionalization, we detected microbial‐induced cellular reactive oxygen species (ROS) in the gut followed by Nrf2 pathway activation and consequent ARE (Antioxidant Response Element)‐dependent cytoprotective gene expression. Nrf2/ARE pathway‐dependent cytoprotection is well established in many tissues, but stimulation by gut bacteria is completely unrecognized. In addition, conventionalized germ‐free animals exhibit higher tonic levels of redox‐responsive genes which may function to maintain the basal cytoprotective response within the mucosa. These results are consistent with recent studies suggesting that bacterial‐host crosstalk is mediated in part by the rapid cellular generation of ROS. Together, these data show that gut microbial‐dependent ROS generation modulates the Nrf2 signaling pathway thus maintaining intestinal epithelial homeostasis and cytoprotection.
Therapeutic administration of a direct thrombin inhibitor reduces hepatic inflammation in a mouse model of hypercholesterolemia
Authors: Kassel Karen M. , Sullivan Bradley P. , Copple Bryan L. , Luyendyk James P.
Published: June 2021

Deficiency in the thrombin receptor protease activated receptor‐1 reduces hepatic inflammation and steatosis in mice fed a Western diet. We tested the hypothesis that thrombin inhibition could reverse hepatic steatosis and inflammation in mice with established diet‐induced fatty liver disease. LDLr−/− mice were fed a control diet or a Western diet for 19 weeks. Mice were given either the direct thrombin inhibitor argatroban or its vehicle for the final 4 weeks. Argatroban administration reduced macrophage and neutrophil accumulation in livers of mice fed a Western diet. Similarly, in mice fed a Western diet, argatroban administration reduced hepatic expression of MCP‐1, ICAM‐1, and MIP‐2, three mediators that can contribute to hepatic macrophage and neutrophil accumulation. In addition, argatroban tended to reduce hepatic steatosis, as indicated by hepatic triglyceride levels. Argatroban completely reversed the increase in serum triglycerides and reduced total serum cholesterol levels in mice fed a Western diet. Argatroban also reduced the expression of profibrogenic genes encoding Type 1 collagen and TIMP‐1 in livers of mice fed a Western diet. Overall, this study indicates that therapeutic intervention with a thrombin inhibitor rapidly reduces several features of diet‐induced NAFLD in mice. This work was supported by AHA Grants 0835121G and 11POST7430043 and by NIH Grants R01 ES017537 and DK073566.