bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a high carbohydrate or a high fat diet and exercise on the oxidant/antioxidant status in liver
Authors: Valdes-Ramos Roxana , Guadarrama Ana Laura , Martinez-Carrillo Beatriz Elina , Kormanovski Alexandre , del Rocio Cruz Hernandez Teresita
Published: June 2021

Mexico has the largest percentage of obese adults worldwide with a diet high in simple carbohydrates, low in non‐industrialized cereals and tubers, and increased in high fat animal foods. It is necessary to evaluate the oxidant‐antioxidant and immune systems affected by diets. To evaluate the effect of a high carbohydrate (HCD) and a high fat diet (HFD) and 9 weeks of exercise (E) on liver and serum oxidant‐antioxidant status, three‐week old male Balb/c mice were evaluated for protein (carbonyls) and unsaturated fatty acid (TBARS) stress indicators, total antioxidant status (TAS) and glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activity in liver homogenates. Carbonyls (8.68±1.25 nmol/mg protein) and TBARS (0.87±0.26 nmol/mg protein) were higher (F=31.096 p<0.001 & F=43.52 p<0.001 respectively) in controls (C) compared to all experimental groups. TAS (F=40.54 p<0.001) was highest in C (3563.37±862.36 nmol/mg protein). All enzymes were decreased. Experimental diets increased the function of the respiratory chain in mitochondria decreasing ROS production and oxidation. The non‐enzymatic portion counteracted diet, exercise and their combination effects. Financed by UAEM and conducted in conformance with FASEB's Statement of Principles for use of animals in research and education. ALGL's graduate studies were funded by CONACyT.
Insights into Prion Biology: Protein Misfolding in its Cellular Environment
Authors: Serio Tricia
Published: June 2021

Protein misfolding and assembly into ordered, self‐templating aggregates (amyloid) has emerged as a novel mechanism for regulating protein function. For a subclass of amyloidogenic proteins known as prions, this process induces transmissible changes in normal cellular physiology, ranging from neurodegenerative disease in animals and humans to new traits in fungi. The severity and stability of these altered phenotypic states can be modulated by the conformation and sequence of the prion, but in most of these cases, the protein retains the ability to form amyloid in vitro. Thus, our ability to link the amyloid assembly pathway with its biological consequences in vivo remains a challenge. In our recent studies, we have begun to address this divide by assessing the effects of the cellular environment on traits associated with the misfolding of the yeast prion Sup35. Remarkably, the effects of changes in quality control pathways and of limitations on protein transfer in vivo amplify the effects of even slight differences in the efficiency of Sup35 misfolding, leading to dramatic changes in the associated phenotype. Together, our studies suggest that the interplay between protein misfolding pathways and their cellular context is a crucial contributor to prion biology.
Role of autophagy in cancer
Authors: White Eileen
Published: June 2021

Autophagy is a catabolic pathway used by cells to support metabolism in response to starvation and to clear damaged proteins and organelles. Autophagy can maintain tissue health and suppress degeneration and cancer initiation, and in this context autophagy is a tumor suppressor. Autophagy, however, is also a survival pathway used by both normal and cancer cells to sustain metabolism and tolerate stress, and in this context autophagy is a tumor promoter. We found that activation of a powerful oncogene such as Ras up‐regulates basal autophagy, which is required for tumor cell survival in stress and in tumorigenesis. In Ras‐expressing cells, defective autophagy causes accumulation of abnormal mitochondria, reduces oxygen consumption and causes tricarboxylic acid (TCA) cycle metabolite and energy depletion in metabolic stress. As mitochondria sustain viability of Ras‐expressing cells in starvation, autophagy is required to maintain the pool of functional mitochondria necessary to support growth and survival of Ras‐driven tumors. As cancers with Ras mutations have a poor prognosis, this “autophagy addiction” suggests that targeting autophagy and mitochondrial metabolism are valuable new approaches to treat these aggressive cancers.
Role of MCT1 in cancer metabolism
Authors: Christofk Heather
Published: June 2021

Many cancer cells exhibit an altered metabolism characterized by increased aerobic glycolysis known as the Warburg effect. To elucidate transcriptional events necessary for the Warburg effect in cancer, we compared gene expression profiles from glycolytic versus less glycolytic breast tumors and cancer cell lines. Amongst the mRNAs that significantly correlated with glycolytic phenotype was one encoding monocarboxylate transporter 1 (MCT1). MCT1 facilitates proton‐linked transport of lactate, pyruvate, and other monocarboxylates across the plasma membrane. We found that MCT1 levels are elevated in malignant breast lesions, and high MCT1 expression predicts poor prognosis in breast cancer patients. MCT1 LOF results in decreased glucose consumption rates in multiple breast cancer cell lines; however, MCT1 LOF does not consistently result in altered lactate production rates. Surprisingly, our data suggests that MCT1 primarily functions to export pyruvate, and that breast cancer cell lines export significant amounts of pyruvate. MCT1 LOF dramatically reduces breast cancer cell proliferation by causing a G1 cell cycle arrest, and reduces mammary fat pad tumor xenograft formation. Together, these data show MCT1 to be critical for breast cancer cell metabolism and proliferation, and suggest that MCT1 inhibitors may be effective anti‐cancer agents.
The Biosynthesis of Polysialic Acid: A Developmentally Regulated, Anti‐Adhesive Glycan
Authors: Colley Karen Jane , Thompson Matthew G , Foley Deirdre A , Zapater Joseph L
Published: June 2021

Polysialic acid is a unique glycan that modulates cell adhesion and signaling, and is critical for brain development, neuronal regeneration, and cancer invasiveness. Polysialic acid is found on a limited number of glycoproteins suggesting that polysialylation is a protein‐specific modification that requires an initial polysialyltransferase (polyST)‐substrate protein‐protein interaction. Previously we found that acidic residues on the surface of the first fibronectin type III repeat of NCAM are required for the polysialylation of the N‐glycans on its adjacent immunoglobulin domain. Using competition and polysialylation assays we have identified a polyST polybasic region that is involved in substrate recognition. Truncated, catalytically inactive ST8Sia IV (PST) proteins containing this region are effective inhibitors of NCAM polysialylation. Replacing Arg82 and Arg93 in region substantially decreases NCAM polysialylation by PST without equally compromising enzyme activity, and also eliminates the ability of a catalytically inactive PST mutant (H331K) to block NCAM polysialylation. In contrast, replacing only Arg82 eliminates the ability of PST to polysialylate SynCAM 1 and neuropilin‐2. These results suggest that the polySTs may use distinct but overlapping basic sites to recognize different substrates. Supported by NIH RO1 GM063843 (KJC) and NIH F31 GM096739 (JLZ).
Self‐Organization of Transitional ER Sites
Authors: Glick Benjamin , Liu Yang , Bharucha Nike , Montegna Elisabeth , Bhattacharyya Dibyendu
Published: June 2021

We are studying the biogenesis and dynamics of transitional ER (tER) sites using the budding yeast Pichia pastoris. Previously, we showed that P. pastoris tER sites are long‐lived structures that form de novo, fuse upon collision, and grow or shrink to attain a steady‐state size. This behavior can be explained by a self‐organization model. Specifically, we postulate that capture of new tER components is balanced by shrinkage driven by the budding of COPII coated transport vesicles. To test this model, we used a genetic screen to identify Sec16 as a key player in tER organization. Sec16 is a large peripheral ER membrane protein that interacts with multiple COPII components. Our results suggest that Sec16 acts as a negative regulator of ER export. According to this view, Sec16 functions primarily to control tER dynamics rather than to nucleate tER site formation. Sec16 defines a new level of regulation for the ER export system.
How Metabolism Informs Cancer Drug Discovery
Authors: Biller Scott A
Published: June 2021

Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are metabolic enzymes that catalyze the oxidative decarboxylation of isocitrate to α‐ketoglutarate (αKG) in the cytoplasm/peroxisomes and mitochondria, respectively. Mutations in either IDH1 or IDH2 were identified in more than 70% of grade II–III gliomas as well as secondary glioblastomas, approximately 20% of patients with acute myeloid leukemia, and more recently in a significant proportion of cartilaginous tumors. We have previously demonstrated that IDH1R132, IDH2R140 and IDH2R172 mutant enzymes display decreased ability to catalyze the oxidation of isocitrate and acquire the ability to catalyze the reduction of αKG to the D‐2‐hydroxyglutrate (D‐2HG). The metabolic convergence of mutant IDH enzymes towards the production of 2HG supports the notion that this metabolite is linked to malignancy. Recent studies have shown that 2HG interferes with the activity of members of the superfamily of αKG‐dependent dioxygenases that catalyze a wide range of biochemical reactions whose deregulation has been associated with malignancy. Thus, the metabolic product of mutant IDH1 and IDH2 enzymes could impact an array of cancer relevant processes, including epigenetics and gene transcription. Based on the genetics and emerging prognostic correlations, mutant IDH1 and IDH2 have emerged as potential therapeutic targets. To that end, we have made significant progress in the identification of selective small molecule inhibitors and in understanding the biology of IDH mutations and D‐2HG. The therapeutic potential of targeting mutant IDH enzymes is currently being evaluated.
SREBP‐1a, lipid metabolism and the innate immune response
Authors: Im Seung-Soon , Osborne Timothy F
Published: June 2021

Recent reports suggest a connection between primary lipid metabolic pathways and other physiologic processes that are influenced by cellular lipid levels. The sterol regulatory element binding protein (SREBP) transcription factors have been demonstrated to be required for these connections through coordinating the expression of genes required for key physiologic processes as well as genes encoding key enzymes of intermediary lipid metabolism. Expression levels for the three individual mammalian SREBPs vary dramatically across different tissues. The SREBP‐1a isoform is abundantly expressed in macrophages and our recent studies showed that it couples lipid synthesis to the proinflammatory branch of the innate immune response. We have extended these observations to provide evidence that SREBP‐1a also regulates two additional branches of the macrophage innate defense response against pathogen engagement including the pro‐survival antiapoptotic response following exposure to bacterial pore‐forming toxins as well as phagocytosis. These studies will be integrated into a model for how SREBPs have evolved to more broadly couple lipid synthetic pathways with the host‐environment interface.
Effects of mycobacteria or HIV on the host antimicrobial peptide cathelicidin
Authors: Flores Sonia C. , Honda Jennifer R.
Published: June 2021

The incidence of nontuberculous mycobacteria (NTM) infections is rising particularly in immunocompromised hosts. Understanding host‐pathogen interactions that allow NTM to gain a foothold is crucial. Antimicrobial peptides (AMPs) are novel host innate antibiotics whose increased production at sites of infection limits bacterial growth and dissemination. The human AMP cathelicidin (LL‐37) is found at mucosal surfaces, neutrophils and bodily fluids and is bactericidal for a variety of bacteria. We tested the activity of LL‐37 against a panel of 4 clinical and 1 environmental NTM isolates and found that although synthetic LL‐37 killed gram‐negative E. coli, it had no effect on NTM. Importantly, whereas the LL‐37 in E. coli culture media (CM) retained antibacterial activity, LL‐37 in NTM CM did not, suggesting a soluble factor in the NTM CM inactivates LL‐37. This factor is partially resistant to heat‐inactivation and is found in the de‐lipidated fraction of NTM cell wall and whole cell extracts. These findings suggest a novel NTM virulence mechanism for evasion of innate immunity. We then measured circulating LL‐37 levels in plasma from HIV−/+ donors. LL‐37 levels were considerably lower in HIV+ compared to HIV‐ (p=0.015). In contrast, PBMC from HIV+ contained more intracellular LL‐37 compared to HIV‐ (p=0.004). Neutralization of LL‐37 activity or altered levels will have significant clinical consequences.
Effects of leucine on mitochondrial biogenesis and cell cycle in A‐375 melanoma cells
Authors: Filhiol Tia M , Johnstone Megan E , Zemel Michael B
Published: June 2021

Most cancer cells undergo the Warburg effect, a shift from oxidative to glycolytic metabolism accompanied by suppression of p53. We have demonstrated leucine to stimulate mitochondrial biogenesis, fatty acid oxidation and p53 in both muscle and fat cells. Accordingly, we now sought to determine if leucine stimulates mitochondrial biogenesis and exit from the cell cycle in A‐375 melanoma cells grown under both standard (11.1 mM) and reduced (5.5 mM) glucose conditions. Increasing glucose reduced mitochondrial mass 50–60% and accelerated cell proliferation by ~20%. Leucine (0.25 – 1.0 mM) dose‐responsively increased mitochondrial mass by 20–40% (p<0.001) under low glucose; its metabolite β‐hydroxy‐β‐methyl butyrate (50 μM) exerted similar effects, while amino acid controls valine and alanine exerted little effect (16–19% stimulation, p<0.05). In contrast, treatments were without significant effect under high glucose conditions. Despite the increase in mitochondrial mass at low glucose, treatments exerted no effect on cell proliferation, p53 or cyclin D. Thus, although both glucose reduction and increased leucine stimulate mitochondrial biogenesis, these effects are insufficient to stimulate p53, induce cell cycle arrest or reduce proliferation in these melanoma cells.
Cinnamon counteracts the negative effects of a high fat/high fructose diet on brain insulin signaling and behavior
Authors: Qin Bolin , Canini Frederic , Roussel Anne Marie , Anderson Richard A
Published: June 2021

Insulin resistance leads to memory and brain impairment. Cinnamon (CN) improves whole body insulin sensitivity but its effects in the brain are not known. Insulin signaling related gene expression in the brain and tests of behavior were measured in male Wistar rats fed a high fat/high fructose (HF/HFr) diet to induce insulin resistance, with or without CN, for 12 weeks. The HF/HFr diet induced an increase in genes coding for PTEN, AKT, amyloid precursor protein, tau, and glycogen synthase and a decrease in genes coding for the insulin receptor and insulin receptor substrates 1 and 2 in the cortex and hippocampus that was counteracted by feeding CN. The CN fed rats were more active and curious in a Y maze test then rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. Diet and CN effects on cognition were not significant. In summary, the negative effects of a HF/HFr diet on brain insulin signaling and behavior were alleviated by CN suggesting neuroprotective effects of CN associated with improved insulin sensitivity.(Funded by USDA/ARS/USA CRADA:58‐3K95‐7‐1184 and French PNRA 007)
Plum polyphenolics prevent adipogenesis, inflammation and obesity‐induced metabolic disorders in obese Zucker rats
Authors: Noratto Giuliana Doris , Simbo Sunday , Martino Hercia S , Byrne David , Mertens-Talcott Susanne
Published: June 2021

Obesity is a risk factor leading to inflammation and chronic diseases. We investigated how peach and plum polyphenolics can prevent metabolic disorders in obese Zucker rats. Experimental groups were feed with peach or plum juice ad libitum, the placebo and lean Zucker groups received same amount of sugars as peach and plum juices in drinking water. Body weights were weekly recorded and serum and fat tissue analyzed after 11 weeks. Results showed that body weight gain on the plum group was lower (p<0.05) than the peach and placebo groups, and this was correlated with increased leptin levels in serum (3‐fold of placebo); accordingly, peach and plum groups had lower levels of glucose (0.77‐fold), triglycerides (0.79‐and 0.75‐fold), and HDL cholesterol (0.47‐ and 0.40‐fold) than placebo group. Plum polyphenolics also exerted the highest antiadipogenic and antiinflammatory effects in fat tissue as demonstrated by decreased mRNA levels of PPAR (peroxisome proliferator‐activated receptor) γ2 (0.46‐fold), IL‐6 (0.52‐fold) and VCAM‐1 (0.58‐fold) and induced the expression of secretory leucocyte protease inhibitor (SLPI) (1.35‐fold), a protein involved in decreasing IL‐6 and inflammation in fat tissue. Overall, plum juice protected against inflammation and metabolic disorders at higher extent than peach juice and this was due to the higher content of polyphenolics (1270 vs 430 mg gallic acid equiv./mL).

Grant Funding Source : ASN
The addition of preformed vitamin A, but not orange‐fleshed sweet potato with high beta‐carotene content, to rice‐based meals reduces zinc absorption in vitamin A‐depleted Bangladeshi women
Authors: Perez-Exposito Ana , Hossain Bakhtiar , Woodhouse Leslie R , Haskell Marjorie J , Jamil Kazi M , Islam M Munirul , Peerson Janet M , Brown Kenneth H
Published: June 2021

The effect of vitamin A on zinc absorption in humans is unknown. We examined the independent effects of vitamin A or beta‐carotene intake and vitamin A status on zinc absorption in vitamin A‐depleted women (plasma retinol <1.05 mmol/L). Zinc absorption from meals with and without vitamin A added and containing high or low beta‐carotene was assessed using stable isotopes before and after 60 days of controlled feeding with white‐fleshed sweet potato (WFSP) + oil capsule, orange‐fleshed sweet potato (OFSP) + oil capsule, or WFSP + vitamin A capsule. Fractional zinc absorption from meals with vitamin A added was lower than zinc absorption from meals with no vitamin A [29.8 ± 6.6 vs. 37.2 ± 9.0 %, p < 0.0001], both before and after the 60‐day controlled feeding period. No difference in zinc absorption from diets containing WFSP or OFSP was found at either time point, and there was no effect of treatment group after the intervention. The addition of vitamin A to rice‐based meals reduces zinc absorption while absorption is not affected by consumption of OFSP with high beta‐carotene content. Intake of OFSP or vitamin A supplements for 60 days does not affect zinc absorption following intervention in vitamin A‐depleted Bangladeshi women. Funding provided by the HarvestPlus Project and the International Nutrition Foundation Fellowship Program.
Acute neurocognitive effects of multi‐vitamin/mineral preparations on brain imaging assessed with Steady State Topography and fMRI during periods of mental effort
Authors: Scholey Andrew , Maggini Silvia , Camfield David , Bauer Isabelle , Neale Chris , White David , Savage Karen , Stough Con
Published: June 2021

The objective of this study was evaluate the acute effects of multi‐vitamin/mineral preparations, both with and without guaraná, on cognitive function and brain activation.

Fifteen healthy young adults took part in a double‐blind, placebo‐controlled crossover study. Cognitive function was assessed 30 min following placebo, a multivitamin/mineral (MV) preparation (Berocca Performance™) and a MV preparation with guaraná (Berocca Boost™) with a > 48 h washout period. Brain bioelectric activity was assessed using Steady State Tomography (SST), a methodology which is sensitive to nutritional interventions. An additional 5 participants underwent functional magnetic resonance imaging (fMRI) during information processing tasks. Berocca Boost™ improved working memory performance which may be attributable to its guaraná content. The two MV treatments resulted in differential patterns of brain activation using both SST and fMRI which were consistent with improved neural efficiency during activation tasks. These data demonstrate that multi‐vitamin/mineral administration can acutely improve neurocognitive functioning by increasing neural efficiency.

This research was supported by Bayer AG.
BRCA‐1 Promoter Hypermethylation and Silencing Induced by the Aromatic Hydrocarbon Receptor and Preventative Effects of Resveratrol
Authors: papoutsis andreas , Borg Jamie , Selmin Ornella , Romagnolo Donato
Published: June 2021

Epigenetic alterations, such as histone and DNA modifications, have been proposed to play a key role in the onset of breast cancer. In sporadic breast tumors, the BRCA‐1 promoter is hypermethylated, and the expression of BRCA‐1 is reduced in the absence of mutations in the BRCA‐1 gene. Diet is a primary vehicle of exposure to agents that modulate the aromatic hydrocarbon receptor (AhR). Ligands of the AhR include environmental xenobiotics, such as dioxins and polycyclic aromatic hydrocarbons. In addition, many frequently consumed food bioactive components bind the AhR, including the phytoalexin resveratrol (Res). Prenatal exposure to 2,3,7,8 tetrachlorodibenzo (p)dioxin (TCDD) increases the susceptibility to mammary cancers in adult offspring in a rat mammary model. The hypothesis of this project is that the recruitment of the activated AhR to the BRCA‐1 promoter initiates a multistep process leading to chromatin modifications that silence the BRCA‐1 gene through promoter methylation and increase susceptibility of mammary tumors. Conversely, these epigenetic alterations are prevented by Res. Previously we documented that exposure of MCF‐7 cells to TCDD represses estrogen‐dependent activation of BRCA‐1 and induces methylation of CpG islands in the BRCA‐1 promoter. In contrast, Res prevents TCDD‐induced recruitment of the AhR; DNA methyltransferase (DNMT)‐1, DNMT3a, and DNMT3b to the BRCA‐1 gene; and BRCA‐1 promoter methylation. We report that prenatal exposure to TCDD in Sprague Dawley rats decreases whereas Res increases BRCA‐1 protein expression in mammary tissue. In addition to Res antagonizing these effects in mammary tissue, we report that it increases the recruitment of the aromatic hydrocarbon receptor repressor (AHRR) which may play a role in inhibiting the translocation of the AhR to xenobiotic responsive elements (XRE) harbored in the BRCA‐1 promoter.
Chemopreventative phytochemical 3,3′‐diindolylmethane inhibits histone deacetylases in prostate cancer cells
Authors: Beaver Laura Michelle , Yu Tian-Wei , Sokolowski Elizabeth I , Hsu Anna , Williams David E , Dashwood Roderick H , Ho Emily
Published: June 2021

Increased consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. Indole‐3‐carbinol (I3C) and 3, 3′‐diindolylmethane (DIM), phytochemicals derived from cruciferous vegetables, have shown promise in inhibiting prostate cancer in experimental models. Histone deacetylase (HDAC) inhibition is an emerging target for cancer prevention and therapy. We sought to examine the effects of I3C and DIM on HDACs in prostate cancer cells. I3C had a minimal effect on cell proliferation and had no effect on HDAC activity or expression in androgen insensitive (PC‐3) prostate cancer cells. In contrast, DIM significantly decreased cell proliferation, HDAC activity, as well as HDAC2 and HDAC8 expression in PC‐3 cells. A trend of decreasing expression was observed for HDAC4 and HDAC6. Surprisingly, DIM treatment caused a significant reduction in acetylated histone H4 but an increase in acetylation of the HDAC6 target gene, tubulin. DIM also significantly inhibited HDAC activity in androgen sensitive LnCap cells. These results show that DIM inhibits HDAC activity and may contribute to the anti‐proliferative effects of DIM in the prostate. The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis.

Grant Funding Source : P01CA090890
Incidence of Physical Impairment and Disability in Puerto Rican Adults: The Boston Puerto Rican Health Study
Authors: Castaneda-Sceppa Carmen , Price Lori Lyn , Falcon Luis , Tucker Katherine L.
Published: June 2021

We examined incidence of physical impairment (low handgrip strength, slow gait speed and chair stand time); and disability (difficulty with ≥1 Activity of Daily Living) in the Boston Puerto Rican Health Study two years after baseline measures were taken in 1166 adults (45–75 y) with no impairment. Stepwise logistic regression models for each impairment and disability outcome were run with the following candidate baseline variables: components of the metabolic syndrome, C‐reactive protein (CRP >3.0 mg/dL), vitamin D deficiency (<15 ng/mL), age (≥60 y), sex, poverty, smoking, and physical activity score; adjusted for the time (25±5 mo) between baseline and follow‐up visits. Male participants as well as those living in poverty and having high blood pressure were more likely to develop handgrip impairment. Age, poverty, and high CRP were associated with incident low gait speed (<0.8 m/s). Incident impaired chair stand time (≥11.2 s) was associated with poverty and abdominal obesity, while high blood pressure was not. Women were more likely than men to develop ADL disability (All P<0.05). These findings underline a possible role of poverty in the development of physical impairment, independent of known factors that contribute to the disablement process. They suggest that factors upstream to the individual should be considered when addressing population health disparities. Support: NIH P01AG023394 and P50HL105185.
The early breastfeeding experience of obese mothers‐ a mediation analysis
Authors: Maalouf-Manasseh Zeina , Dewey Kathryn G , Chantry Caroline J , Peerson Janet M , Nommsen-Rivers Laurie
Published: June 2021

Maternal obesity is associated with poor breastfeeding (BF) outcomes. We used the Early Lactation Success cohort to determine mediators of the relationship between maternal obesity and early BF outcomes in 405 primiparae who delivered at term and initiated BF. We used validated instruments and in‐person interviews to collect data prenatally and at 0, 3, and 7 d postpartum. Compared to non‐obese women (BMI<25, n=121), obese women (BMI>30, n=130) were more likely to have a C‐section (45% vs. 22%, P=0.0003), postpartum edema (85% vs 27%, P<0.0001) and to be separated from the baby for >2h immediately after birth (24% vs. 7%, P=0.0003). Obese women were more likely to have: introduced BF after 2 h postpartum (30% vs 18%, P=0.03, delayed onset of lactogenesis (delayed OL, 54% vs. 31%, P=0.02), and infants with sub‐optimal BF behavior at d 7 (SIBB D7, 33% vs. 15%, P=0.02). Obese women also BF less often on d 0 (8.6 vs. 9.5, P=0.03). Cesarean delivery and postpartum separation mediated 25% and 78%, respectively, of the relation between obesity and delay in the 1st BF. Postpartum separation mediated 48% of the relation between obesity and BF frequency on d 0. Edema mediated 35% and 25%, respectively, of the relations between obesity and delayed OL and SIBB D7, respectively. Strategies to improve BF outcomes in obese women should include minimizing unnecessary cesarean delivery and separation of the dyad. Research support provided by the Department of Health and Human Services, Maternal Child Health Bureau (KGD) and the National Institute of Child Health & Human Development (LAN‐R).

Grant Funding Source: Department of Health and Human Services, Maternal Child Health Bureau
Lower dairy calcium and dairy vitamin D intakes are associated with increased skeletal muscle fatty infiltration in adolescent girls
Authors: Vassallo Danielle , Lee Vinson , Laudermilk Monica , Blew Rob , Going Scott
Published: June 2021

BACKGROUND

Fat infiltration within skeletal muscle is strongly associated with type 2 diabetes mellitus. Insufficient calcium (Ca) and vitamin D (VitD) intake is common in youth and has been associated with the development of obesity and osteoporosis. Dairy Ca and VitD are better absorbed compared to other dietary sources and have been linked to decreased adiposity.

OBJECTIVE

Examine the relationships between dairy Ca and VitD with skeletal muscle fat infiltration (SMFI) in 212 healthy girls aged 8–13 years.

METHODS

Muscle density (mg/cm3), an index of fat infiltration, was measured at the 66% tibia and 20% femur sites (relative to distal growth plates) on the non‐dominant limb using peripheral quantitative computed tomography (pQCT). Dairy Ca and VitD were assessed using the Harvard youth adolescent questionnaire (YAQ).

RESULTS

Multiple linear regressions with dairy Ca and VitD, maturity, total caloric intake, and activity (pedometer steps) were used to predict SMFI and showed that dairy Ca was positively associated with muscle densities of the calf (P ≤ 0.01, partial r (ρ)=0.185, β=0.216) and thigh (P ≤ 0.05, ρ=0.135, β=0.157 ). Dairy VitD was independently associated with higher muscle densities of the calf (P≤ 0.01, ρ=0.183, β=0.194) and thigh (P ≤ 0.05, ρ=0.159, β=0.168).

CONCLUSION

Lower dairy consumption is associated with increased SMFI in young girls.

Grant Funding Source : NIH: HD050775
Inflammation, iron status, and growth of school‐age children: a prospective study
Authors: Perng Wei , Baylin Ana , Marin Constanza , Mora-Plazas Mercedes , Villamor Eduardo
Published: June 2021

Objective

To investigate associations of four markers of inflammation, C‐reactive protein (CRP), ferritin, white blood cell count (WBCC), and neutrophil count (NC), with changes in adiposity and linear growth in a longitudinal study of school‐age children from Bogotá, Colombia.

Methods

We quantified CRP, ferritin, WBCC, and NC from samples collected among 2708 children aged 5–12 y at baseline. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in age‐ and sex‐standardized BMI‐ and height‐for‐age Z‐scores and waist circumference according to quartiles of each inflammatory marker at baseline using multivariable mixed effects linear regression models.

Results

There were no associations between any of the subclinical inflammation biomarkers and change in indicators of adiposity over follow‐up. However, ferritin serostatus was inversely related to linear growth after adjustment for CRP, an independent indicator of inflammation, and potential confounders. Compared to children in the lowest quartile of ferritin, those in the highest quartile had an annual change in height‐for‐age that was 0.03 Z lower (P trend=0.001).

Conclusion

CRP, ferritin, WBCC, and NC do not predict weight gain in school‐age children. However, high iron status, indicated by CRP‐adjusted ferritin concentrations, may be related to slower linear growth.

Grant Funding Source : University of Michigan Center for Global Health
Comparison of phenolic acid profiles and anti‐inflammatory effects of two major species of blueberries in the US
Authors: Kang Jie , Thakali Keshari M , Wu Xianli
Published: June 2021

Blueberries (BB) contain high levels of polyphenols. Among them, phenolic acids (PAs) have been recently suggested as a group of important bioactive compounds. Highbush BB (Vaccinium corymbosum) and lowbush “wild” BB (Vaccinium angustifolium) are two predominant species in North America. The first objective of this study is to systemically analyze and compare the profiles of PAs in these two species. Nine PAs were detected and quantified in both species by HPLC/MS; of these, five PAs were identified in BB for the first time. The total PA content of lowbush BB (4.90 mg/g, dry weight (DW)) is about 3.2 times higher than that of highbush BB (1.53 mg/g, DW). Chlorogenic acid is the most abundant PA in BB, at 4.87 mg/g DW and 1.12 mg/g DW in lowbush and highbush BB. Anti‐inflammatory effects of polyphenol‐rich extracts of the two BB species were evaluated by a SEAP reporter assay to measure NF‐κB activation. An initial test using 10 μg/mL of extracts showed that lowbush and highbush BB inhibited LPS‐induced NF‐κB activation by 30.7 % and 16.8 % (P<0.05), respectively. Our data indicated that the concentrations of phenolic acids in the two major BB species are very different. Lowbush BB polyphenols exhibited greater anti‐inflammatory potential than those of highbush BB. The anti‐inflammatory effects of polyphenols in BB warrant further investigation. (USDA‐CRIS‐ 6251‐5100002‐06S)
Soluble corn fiber (SCF) effects on calcium absorption and retention in adolescent girls and boys
Authors: Whisner Corrie Marie , Martin Berdine R , Clavijo Andrea , Nakatsu Cindy H , McCabe George P , McCabe Linda D , Weaver Connie M
Published: June 2021

This study evaluated the effect of SFC on calcium absorption and retention in adolescent boys and girls. Calcium absorption and retention were studied in a three‐week metabolic balance double‐blind, randomized, cross‐over design with a controlled background diet containing 600 mg daily calcium and treatments of either 0 and 12 g/d SCF. Diet composites, fecal and urine samples were collected daily and analyzed for calcium. In the third week of treatment, 44Ca and 43Ca were administered and fractional calcium absorption was calculated as the ratio of excess 44Ca and 43Ca in the urine after accounting for natural abundance. Pairwise comparisons revealed a significant difference in fractional calcium absorption in 24 h – 48 h urine samples; SCF treatment increased absorption by 12% (70 mg/d) compared to control (0.664 ± 0.129 and 0.595 ± 0.142, respectively; p<0.03). SCF treatment had no overall effect on calcium balance, but this was likely due to the insensitivity of balance as urinary Ca only increased by 10 mg/d (NS) with consumption of SCF. The increase in fractional calcium absorption with SCF consumption may be due to increased absorption in the lower gut through alterations in colonic bacterial profiles that enhance calcium absorption.

Grant Funding Source : Tate & Lyle Health & Nutrition Sciences
Gestational Weight Gain is associated with Postpartum Weight Retention and Infant Anthropometrics
Authors: Begum Fatheema , Colman Ian , McCargar Linda , Bell Rhonda C ,   APrON Study Team
Published: June 2021

Optimal gestational weight gain is essential for healthy pregnancy outcomes. The study objective is to describe the association between gestational weight gain and early postpartum weight retention, and infant anthropometrics at birth and 3 months. Pregnant women (n=600) were followed up 2–3 times during pregnancy and at 3 months postpartum. Data on maternal weight at pre‐pregnancy, during pregnancy and postpartum were collected. Women were categorized as, “Below”, “Met” or “Above” based on the 2010 Gestational Weight Gain Guidelines. Infant birthweight and weight and length at 3 months were available. Age and sex specific z‐scores were calculated for birthweight and infant anthropometrics at 3 months. Data were analysed using regression. Over 55% women gained above recommended guidelines. Overweight (OR = 5.5, p <0.001) and obese (OR = 6.5, p <0.001) women were more likely to gain excess weight when compared to normal weight women. In comparison to adequate gestational weight gain, excessive weight gain was associated with higher postpartum weight retention (ß = −3.03, p <0.001), birthweight z‐scores (ß = 0.34, p <0.01), infant weight for age z‐score (ß = 0.40, p <0.01), and infant BMI z‐score (ß = 0.55, p <0.05). Excessive gestational weight gain promotes obesity in mothers and higher weights in infants. Interventions that optimize weight gain may significantly affect the long‐term health of women and children.

Grant Funding Source: Alberta Innovates ‐ Health Solutions
Demographic, Environmental and Psychosocial influences on the Physical Activity of Adolescents from Diverse Ethnic Groups: Structural Equation Modeling Analysis
Authors: Hilmers Angela , Chen Tzu-An , Cullen Karen
Published: June 2021

Objectives

This study explored the direct and mediation effects of five important psychosocial constructs related to physical activity (PA) in youth.

Methods

Participants were 411 adolescents aged 12–17 years. Demographics, neighborhood environment, home media exposure and media use, psychosocial variables (self‐efficacy, perceived behavioral control, social support, and enjoyment) and PA were assessed using validated measures. Mediation and moderation effects were examined using structural equation modeling.

Results

Social support was the strongest predictor of PA mediating the effect of the neighborhood environment on PA among males, overweight/non‐overweight and low‐income/minority adolescents. Enjoyment was inversely associated with media use in females and low‐income/minority adolescents but not in males or Caucasians.

Conclusions

Social support appears to be the most important contributor to PA in males. Adolescents at higher risk for inactivity (i.e., females, low‐income/minority adolescents) may respond differently to PA promotion depending on their levels of PA enjoyment. Low levels of PA enjoyment may increase home media use and lead to a decrease in regular PA. Lack of mediation effects from efficacy cognitions suggests the need for further exploration of individual factors predicting engagement in PA among adolescents. This study was funded by the USDA/ARS.

Grant Funding Source : USDA/NRI/AFRI
Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice
Authors: Yan Lin , Demars Lana C
Published: June 2021

The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA), in comparison with selenomethionine (SeMet), on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN93G control diet or that diet supplemented with MSeA or SeMet at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 × 105 viable LLC cells. Experiments were terminated 2 weeks later for mice injected intramuscularly or 2 weeks after surgical removal of primary tumors from mice subcutaneously injected with cancer cells. Dietary supplementation with MSeA significantly reduced pulmonary metastatic yield compared with the controls (P < 0.05) in both models; however, SeMet did not have such an effect. Supplementation with MSeA significantly lowered plasma concentrations of uPA (P < 0.05) and PAI‐1 (P < 0.05). Furthermore, MSeA significantly reduced plasma concentrations of VEGF (P < 0.05), FGF‐basic (P < 0.05) and PDGF‐BB (P < 0.05) compared with the controls. Selenomethionine did not affect any of the aforementioned measurements. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis.
Polyphenolic Extract from Mangifera indica is Cytotoxic in ER + BT474 Breast Cancer Cells and Targets the SHIP‐1‐Phosphatidylinositol3‐kinase (PI3K)‐Akt through microRNA‐155
Authors: Banerjee Nivedita , Arbizu Shirley , Krenek Kimberly A , Talcott Susanne Mertens
Published: June 2021

The objective of this research was to understand the post‐transcriptional targets involved in anti‐inflammatory and pro‐apoptotic pathways in estrogen receptor positive (ER+) breast cancer cells BT474 treated with a polyphenolic extract (2.5–40μg/ml) rich in gallotannins and galic acid from Mangifera Indica L in vitro and in nude mice with BT474 cells as xenografts. Results show that cell proliferation as well as tumor size and weight in vivo was decreased by polyphenolics. NF‐kB protein and mRNA expression as well as activation were decreased in a dose‐dependent manner accompanied by increased expression of IKKα/β kinases, and impaired IκB degradation.

The extract also inhibited PI3K dependent phosphorylation of AKT and increased in SHIP‐1 expression and this was accompanied by down‐regulation of miRNA 155 of BT474 (0.6 fold) and in vivo. Results were confirmed by using a mimic for miR‐155 which in part reversed the effects of the extracts. NFκB‐dependent genes involved in anti‐apoptosis, metastasis and angiogenesis, such as survivin, VCAM‐1, and VEGF were also decreased.

In summary the anti‐carcinogenic and anti‐inflammatory activity of mango polyphenolics in breast cancer cells were at least in part due to targeting miR‐155‐SHIP‐1‐Phosphatidylinositol 3‐kinase (PI3K)‐Akt‐NF‐kB which plays an important role in the proliferative/inflammatory phenotype exhibited in this breast cancer cell line.

Grant Funding Source : NIH
Bioinformatics Approaches for Weight Loss‐induced Cancer Preventive Mechanisms
Authors: Standard Joseph , Jiang Yu , Chen Jin , Lu Lizhi , Tomich John , Welti Ruth , Wang Weiqun
Published: June 2021

Weight control by dietary calorie restriction (DCR) or exercise is associated with cancer prevention in animal models. Bioinformatics analysis of profiling changes was employed to uncover the underlying mechanisms. SENCAR mice were randomly assigned into 4 groups for 10 wks: ad lib‐fed sedentary control, ad lib‐fed exercise (AE), exercise but pair‐fed at the amount of control (PE), and 20% of DCR. Two hrs after topical TPA treatment, skin epidermis were analyzed by Affymetrix for gene expression, DIGE for proteomics, and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67, and 110 genes were significantly changed in DCR, PE, and AE, respectively. Over 600 protein spots were separated, ~120 proteins identified, and 27 proteins significantly changed by DCR. Among 338 phospholipids, five phosphatidylinositol species were decreased in PE but not AE. While gene and protein expression was not always correlated, reduced TPA‐promoted Braf in MAPK pathway and PI3K‐Akt1 in IGF‐1 signaling appeared possible targets for cancer prevention through weight loss (supported by NIH CA167678).
Dietary, Lifestyle, Medical, and Stress‐Relief Choices in Promoting Health
Authors: Wimalawansa Sunil J.
Published: June 2021

Introduction

Lifestyle medicine applies lifestyle interventions such as environmental, behavioral, medical, and motivational principles in the treatment and management of chronic diseases. Physical inactivity and unhealthy eating are major drivers of disease, death, and escalating healthcare costs. Behavioral modification is an important part of preventative medicine & management of chronic diseases, including diabetes, obesity, hypertension, osteoporosis, heart disease, and some cancers. Such diseases can be treated with lifestyle medicine as effectively or more effectively than with medications; but without risks of unwanted effects.

Methods & Insight

Hormones produced by endocrine glands influence every cell, organ, and function of the body. They regulate mood, growth, metabolism, sexual and reproductive processes. Sustained elevation of stress‐hormones such as glucocorticoid and adrenaline has marked negative effects on human health. Sustained and unmanaged stress adversely affects not only the endocrine functions, but also the nervous system, which could result in depression, hypertension, diabetes, obesity, and the like. Such diseases can be effectively treated with lifestyle medicine, by changing dietary and a multitude of personal habits. A key part of lifestyle medicine is to learn and apply, and teach ability of coping with day‐to‐day stresses and means of adapting to rapidly changing circumstances. Such education should be routine parts of medical and nursing educational curricula.

Conclusions

Most human disorders are initiated after maladaptation to stress. Thus, learning and practicing various stress‐reducing methods, such as meditation, Tai‐chi, yoga, exercises, or relaxation methods such as a listening to music or playing a musical instrument can be helpful in alleviating excess stress. A balanced diet and regular exercise together with relaxation of the mind and body can turn the negative spiral of mental and physical imbalance and stresses into a positive impact, ensuring optimum health.

Grant Funding Source: ASN
Burden and Determinants of Childhood Undernutrition in an Urban Slum Community in Ibadan, Nigeria
Authors: Samuel Folake Olukemi , Fadeyi Fadeke Bolupe
Published: June 2021

The objective of this study was to assess the burden and determinants of childhood undernutrition in an urban slum community in Ibadan, Nigeria. A 3‐stage stratified random sampling was used to select 273 children (0–24 months) from one slum community in the city of Ibadan. The prevalence of wasting, stunting and underweight was computed while the burden of undernutrition was calculated using the Composite Index of Anthropometric Failure (CIAF). There were 138 females and 135 males; mean age was 8.5 ± 6.3 months. Prevalence of wasting, stunting and underweight were found to be 9.9%, 47.6% and 21.6% respectively. Age groups 7–12 months and 19–24 months were at significantly higher risk of undernutrition. Using CIAF, six sub‐groups of single and multiple anthropometric failures were computed, giving an overall prevalence 57.1% as burden of undernutrition. Determinants of undernutrition in the community were mainly poor infant and young child feeding practices, poor environment and sub‐optimal care practices. Interventions based on improvement of infant and young child feeding, care and environmental health are needed in this community to reduce the high burden of childhood undernutrition.
Food sources of energy and key micronutrients in diets of the Bangladeshi population
Authors: Bermudez Odilia , Lividini Keith , Smitz Marc-Francois , Fiedler John L.
Published: June 2021

Objective

To estimate food sources of energy and key micronutrients (MN), and assess intakes and risk for inadequate intakes of vitamin A (VA), iron (Fe) and zinc (Zn) in the Bangladeshi population.

Methods

Food acquisition data from the Bangladesh 2005 Household Income and Expenditure Survey (HIES) were used to estimate food sources and intakes of energy (E), VA, Fe and Zn by applying adult equivalents (AEq) for food consumption. Intakes of Fe and Zn were adjusted by bioavailability.

Results

The Bangladeshi population got their energy mainly from rice (71%), soybean oil (5%) and wheat (2%). VA came from spinach (32%), perbol (20%) and gourds (11%); Fe from spinach (28%), rice (23%) and wheat (7%); and Zn from rice (52%), wheat (12%) and spinach (7%). National intake of energy was 2,239 Kcal/AEq, while, for VA, Fe and Zn, intakes were: VA: 306 ug, Fe 0.75 mg and Zn 2.14 per AEq. And proportions of population at risk of inadequate intakes reached 83% for VA, 81% for Fe and 39% for Zn.

Conclusions

Using a national survey (Bangladesh 2005) with data on food acquisition, we estimated apparent food consumption and MN intakes that enabled us to estimate MN intakes, compare them to MN recommendations, and estimate the prevalence of inadequate intakes.

Funding: Bill & Melinda Gates Foundation Grand Challenge 9 grant