bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRTUINS, AGING AND DISEASE
Authors: Guarente Leonard 
Published: June 2021

SIR2 and related genes are NAD‐dependent deacetylases that slow aging in yeast, C. elegans, and Drosophila. In yeast and flies, SIR2 genes are also involved in the longevity conferred by dietary or calorie restriction (CR). The mammalian SIR2 homologs termed SIRT genes, or sirtuins, are involved in changes in stress resistance and metabolism and are known to be associated with CR. Critically, the CR diet in rodents not only extends life span, but also protects against many diseases of aging. In this talk, I will describe recent findings in the lab regarding SIRT1 function in specific mammalian tissues in relation to murine disease models. Our findings indicate that SIRT1 can influence many of the major diseases of aging, includingmetabolic diseases like diabetes, neurodegenerative diseases (Alzheimer's and Huntington's), cancer and osteoporosis. Therefore small molecules that alter the activity of SIRT1 (i.e. CR mimetic drugs) offer a new approach to prevent and possibly treat the major diseases of aging.Supported by NIA, Glenn Foundation, Hi‐Q, HDF, Estee Lauder. Guarente consults for Sirtris/GSKGuarente, L. (2007). Sirtuins in aging and disease. CSH Symp. Quant. Biol. 72, 483–488.Guarente, L. (2008). Mitochondria – a nexus for aging, calorie restriction and sirtuins?. Cell 132, 171–175.
VP Regulatoy, Quality Assurance, Medical & Clinical Affairs
Authors: Barber Cynthia M 
Published: June 2021

The attractiveness of having a science degree is that there is an array of diverse and exciting jobs outside of the laboratory. Currently there is a shortage of regulatory and quality assurance (QA) personnel. And firms are seeking scientists for these position.The need arises because it is crucial that all pharmaceutical, medical device, veterinary, infant nutritional and cosmetic products are registered before they can be marketed for sale. Working in regulatory affairs involves the preparation of scientific and technical information to support product approval globally, keeping abreast of changes in legislation and informing colleagues according. Job roles include quality control and assurance, clinical trial design and management, process development chemist, product formulation scientist, medical writing for regulatory dossiers and acting as a company representative to regulatory agencies.Many companies seek PhD scientist for these positions. Most regulatory agencies employee scientist and there is a need to counter these skills within the company. The expectation is that you bring your scientific research experience and thought process to the company.Learn on the job and after a couple of years experience you will be considered a seasoned regulatory affair and quality assurance professional.
The Dietary Intervention of Tomato and Broccoli for the Prevention of PhIP Induced Prostate Carcinogenesis in Rats
Authors: Canene‐Adams Kirstie , De Marzo Angelo M. 
Published: June 2021

The heterocyclic amine, 2‐ amino‐1‐methyl‐6‐phenylimidazo[4,5‐B]pyridine (PhIP), is found in well‐cooked meats and has been implicated by epidemiology and rodent carcinogenesis studies for causing breast, prostate, and colon cancers. The combination of tomato and broccoli powders has been shown to reduce cancer burden in other models of prostate cancer, but have not been utilized to study PhIP induced prostate carcinogenesis previously. Our objective was to determine if a diet of tomato and broccoli could reduce PhIP induced prostate carcinogenesis. Fifty male Fisher 344 rats were put into 1 of 3 treatment groups, control, PhIP (Nard Institute, Ltd., Japan, 200 ppm in the diet and fed for 20 wks), or tomato + broccoli + PhIP. Tomato and broccoli powders, Future*Ceuticals, Illinois, were mixed into AIN93G diets at a level of 10% each and fed with PhIP for 20 wks, and then without PhIP for an additional 32 wks. Rats were euthanized as needed based on health status and tumor burden and survival rates for each group were calculated. After the 52 wks, all remaining rats were euthanized and various tissues collected for histological analysis.Research support: DOD PCRP and the Maryland Cancer Restitution Fund
The effect of activated‐mitogen activated protein kinase (MAPK) activity on 1,25 dihydroxyvitamin D (1,25D)‐mediated gene transcription in colon cancer cells
Authors: DeSmet Marsha , Fleet James C. 
Published: June 2021

The active form of vitamin D (VD), 1,25D, induces anti‐cancer effects in many cell lines by activating the VD receptor (VDR). In cancer, MAPK pathways (ERK, JNK, p38) are activated and previous research shows that activated MAPK impairs 1,25D action in skin and prostate cell lines. To determine whether activating MAPK influences 1,25D action in colonocytes, Caco‐2 cells were pretreated with an agent that induces multiple MAPK pathways, As2O3, prior to 1,25D treatment. As2O3 decreased 1,25D‐mediated induction of CYP24 mRNA (−55%) but also decreased VDR mRNA levels by 50%. In contrast, a specific JNK activator, anisomycin, did not alter 1,25D‐mediated CYP24 mRNA induction indicating the effect of As2O3 was not due to JNK activation. KRAS activating mutations are common in colon cancer. Caco‐2 cells transfected with either a constitutively active (ca) KRAS plasmid or a caMEK1 plasmid have reduced 1,25 D‐induction of both 3XVDRE (−30%) and CYP24 promoter (−60%) reporter genes. Conversely, in HCT116 colon cancer cells with a RAS‐activating mutation 1,25D‐induced CYP24 mRNA was enhanced 285% by the MEK inhibition. These data demonstrate that a common mutation in colon cancer, i.e. KRAS activation, suppresses 1,25D action in colon cancer cells and may limit the chemopreventive effects of high vitamin D status.Supported by NIDDK Award DK54111 to JCF
Physical Activity Intervention for Osteoporosis Prevention in Black Older Adults
Authors: Babatunde Oyinlola T , Campa Adriana , Himburg Susan P , Newman Frederick L , Dixon Zisca 
Published: June 2021

BackgroundPhysical activity (PA) is one of the lifestyle behaviors considered important in osteoporosis prevention. This study examined the effect of the Revised Health Belief Model theory‐based education program on osteoporosis prevention. The PA component is reported here.Research methodA repeated measure, randomized, wait‐list control design with 6‐weekly education sessions was offered to 130 consented black older adults in community settings in South Florida. The two groups were evaluated on the effect of the program on changes in calcium intake and PA after the program. PA benefits/barriers were discussed and demonstrated along with nutrition topics. PA was measured using Physical Activity, Osteoporosis Self‐Efficacy and other questionnaires based on the constructs of the theory.ResultsA total of 110 (experimental 59, wait‐list 51) completed all assessments. Mean age was 70.15±10.44 yrs and 90.0% were female. Reported PA scores were not significantly different (p>.05, η2 =.02), however osteoporosis self‐efficacy scores indicated participants perceived they could change their behaviors to impact their health (p<.05, η2=.20).ConclusionThough a combined dietary and PA program was effective with an Asian group, this population has more resistance to change PA behavior. Further studies are needed to explore alternative strategies to improve PA in this minority group.Grant Funding Source: N/A
Maternal B‐vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis among offspring in the Apc+/1638N mouse
Authors: Ciappio Eric D , Liu Zhenhua , Mason Joel B , Brooks Ryan S , Bronson Roderick T , Crott Jimmy W 
Published: June 2021

Folate and other B‐vitamins play important roles in DNA methylation, and adequate intakes of these nutrients have been implicated in the prevention of colon cancer. Concentrations of B‐vitamins in the maternal diet may impact disease susceptibility in offspring. Therefore, we investigated the effect of maternal B‐vitamin intake on intestinal tumorigenesis in offspring. Three groups of 6‐week old female C57BL/6 mice were fed diets either deficient, replete, or supplemented with folate, vitamin B2, B6, and B12 for 4 weeks, then mated with male Apc+/1638N mice. Females remained on their respective diets throughout mating, pregnancy and the suckling period (11 weeks total). After weaning, all Apc+/1638N pups were fed a replete diet (AIN‐93), regardless of maternal diet. At 32 weeks of age, 58% and 63% of pups born to deficient and replete mothers, respectively, exhibited tumors in the small intestine compared to 21% of pups born to supplemented mothers (p<0.025). Furthermore, a higher percentage of tumors collected from pups of deficient mothers displayed invasive behavior compared to tumors from pups of replete mothers (p=0.03). These data indicate that maternal B‐vitamin supplementation suppresses tumorigenesis in Apc+/1638N offspring relative to deficient and replete maternal diets and furthermore that maternal B‐vitamin depletion accelerates the acquisition of invasive characteristics in tumors.Grant Funding Source: USDA CRIS # 1950‐5100‐074‐01S
Medicinal herbs inhibit prostate cancer (PCa) via PI3 kinase and p21 mechanisms
Authors: Huang E‐Chu , Chen Guoxun , Baek Seung J , McEntee Michael F , Whelan Jay 
Published: June 2021

Our preliminary data showed that a combination of medicinal herbs is far superior in inhibiting PCa growth compared to individual herbs. We explored the molecular mechanisms responsible for these effects in vitro (22Rv1 PCa cells) and in vivo (using a CWR22 PCa cell xenograph model). Zyflamend®, a mixture containing extracts of 10 medicinal herbs, inhibited growth of 22Rv1 cells (individual herbs had no effect) by inhibiting PI3 kinase activity and downstream signaling, i.e, reductions in pAKT, SREBP‐1c, FAS, androgen receptor (AR), IGF‐1R and induction of p21and p27. Cell cycle inhibitor p21 is commonly lower in PCa, and Zyflamend® dramatically increased and stabilized p21 mRNA and protein through a p53‐independent mechanism. The p21 effects were confirmed with SiRNA experiments. Reductions in cell proliferation coincided with these molecular effects along with increases in apoptosis. This herbal combination (but not individual herbs) suppressed expression of Class I and II histone deacetylases (HDACs), suggesting epigenetic regulation of p21. In vivo, Zyflamend® enhanced tumor regression following androgen withdrawal by inhibiting HDACs, IGF‐1R, and AR expression, all critical in preventing PCa relapse. Our results suggest this herbal combination coordinately affects multiple signaling pathways to inhibit PCa tumor cell growth and promote cell death. (Supported by NewChapter, Brattleboro, VT).Grant Funding Source: NewChaper Inc.
Inhibition of Lung Cancer Cell Growth by Polymethoxyflavones from Sweet Orange
Authors: Charoensinphon Noppawat , Qiu Peiju , Dong Ping , Ngauv Pearline , Xiao Hang 
Published: June 2021

We isolated 6 closely related polymethoxyflavones (PMFs) from sweet orange, and studied their effects on the growth of two human non‐small cell lung cancer cells. The permethoxylated PMFs, namely nobiletin, 3,5,6,7,8,3′,4′‐heptamethoxyflavone (HMF), and tangeretin, showed dose dependant growth inhibition on H1299 and H460 cells. Interestingly, three monohydroxylated PMFs, namely 5‐hydroxyl nobiletin (5HN), 5‐hydroxyl HMF (5HH), and 5‐hydroxyl tangeretin (5HT), that are derived from the three permethoxylated PMFs correspondingly showed much stronger inhibitory effects on the same lung cancer cells than their counterparts. In H460 cells, IC50 of 5HN, 5HH, and 5HT were 6.3, 17.8, and 44.0‐fold lower than those of their permethoxylated counterparts, respectively. Cell cycle analysis revealed that all 6 PMFs caused cell cycle arrest at G0/G1 phase, while 5HH and 5HT also increased G2/M cell population. The Annexin V/PI co‐staining assay revealed that PMFs had different effects on cell death. While other PMFs showed marginal effects on the apoptosis, 5HH and 5HT significantly increased percentage of lung cancer cells undergoing early and late apoptosis by 4 to 6 fold in comparison with the control cells. Our results demonstrated that hydroxylation in the PMF structures enhanced their growth inhibitory effects on human lung cancer cells by potentiating their activities on cell cycle arrest and pro‐apoptosis.Grant Funding Source: University of Massachusetts Amherst
Global improvement in multiple cardiovascular disease risk factors with a medical food containing soy, phytosterols, hops rho iso‐alpha acids, and acacia proanthocyanidins and a Mediterranean‐style low glycemic load diet in women with metabolic syndrome
Authors: McIntosh Mark , Kalynych Colleen J , Vukich Clare , Kumar Vivek , Lott Michelle , Lerman Robert H 
Published: June 2021

We evaluated effects on cardiovascular disease (CVD) risk factors of a Mediterranean‐style, low glycemic load diet (MLGD) alone or in combination with a phytosterol‐soy based medical food (PSS) containing hops rho iso‐alpha acids and acacia proanthocyanidins in women with metabolic syndrome (MetS). Subjects (BMI 25–45 kg/m2, LDL cholesterol (LDL‐C) ≥100 mg/dL, and TG≥150 mg/dL) were randomly assigned to either MLGD+PSS (n=12) or MLGD alone (n=12). No caloric restriction was imposed and exercise was maintained at baseline levels. Improvements in total cholesterol, LDL‐C, and apolipoprotein B (apo B) were noted in both arms (P<0.01). ApoB/apo A1 and insulin were reduced only in MLGD+PSS (P<0.01). Compared to MLGD, MLGD+PSS experienced greater reductions (P<0.05) in apo B at 8 and 12 weeks and in homocysteine at 12 weeks (p<0.05). LDL particle number was decreased at 8 (P<0.005) and 12 weeks (P<0.05) in MLGD+PSS; however, a reduction was found only at 8 weeks (P<0.05) in MLGD. Small LDL particles were decreased at 8 weeks (P<0.005) and trended downward at 12 weeks (p=0.06) only in MLGD+PSS. A downward trend in hsCRP was noted at 12 weeks, only in MLGD+PSS (P=0.07). Supplementation with a medical food containing soy, phytosterols, and specific phytonutrients may enhance benefits of a MLGD in women with MetS leading to global improvement in multiple CVD risk factors.Supported by MetaProteomics, LLC.
Fat oxidation is enhanced in meals containing PUFA from walnuts
Authors: Tapsell Linda Clare , Batterham Marijka Jane , Tan Sze Yen 
Published: June 2021

Polyunsaturated fats (PUFA) are preferentially utilized as fuel rather than stored. Diets containing PUFA rich foods (and perhaps also suitable food matrices) may be advantageous in promoting fat oxidation. Greater fat oxidation may lead to reduced fat mass, the target for weight loss. The aim of this study was to examine the effects on fat oxidation of a walnut based diet compared to a control with olive oil. In a crossover design testing effects of walnuts vs olive oil, 16 overweight adults consumed isocaloric breakfast and lunch meals based on core foods during 8hr in a room calorimeter facility. There was no difference in energy expenditure between the diet phases but fat oxidation was higher during the walnut period compared to the control (RQ for control 0.908 ± 0.046 vs walnut 0.855 ± 0.036, P = 0.029).Under acute conditions this result indicates that the walnut containing meals produced a more favorable fuel utilization profile for body fat loss. Further research would determine whether the acute fat oxidation effect translates to greater loss of body fat in the long term.Source of research support: California Walnut Commission Project Grant.
Maternal autonomy and its influence on pregnancy outcome in India
Authors: Chakraborty Priyanka , Anderson Alex Kojo 
Published: June 2021

ObjectiveThis study aims to examine the influence of women's autonomy on pregnancy outcome (birth weight and birth size).MethodThis is a secondary data analysis of the 2005–2006 National Health and Family Survey (NFHS‐III) of India. Descriptive and logistic regression analyses were performed.ResultThe average age of women included in this study was 25.9 ± 4.9 years. Although, the mean birth weight was 2835 ± 666.4 g, nearly 20% of the index children were born LBW (<2500 g). Lower maternal age, illiteracy, poor socioeconomic status and rural households were significant predictors of both LBW and smaller birth size as reported by the mother. Interestingly, women with lower autonomy had a poor nutritional status (p < 0.001), and were more likely to deliver LBW (OR = 1.4, 95% CI = 1.2 − 1.6, p < 0.001) and small infants (OR = 1.5, 95% CI = 1.3 − 1.7, p < 0.001) as compared to women with a higher autonomy. Lower maternal autonomy remained a significant predictor (OR = 1.3, 95% CI = 1.1 − 1.5, p = 0.006) for both LBW and small size at birth (OR = 1.4, 95% CI = 1.2 − 1.7, p < 0.001), after controlling for maternal socio‐demographic characteristics, parity and birth interval.ConclusionFindings from this study suggest a strong association between maternal autonomy and pregnancy outcome with mothers with low autonomy having a higher risk of delivering a low birth weight baby and also reporting smaller birth size.Funding: Dept of Foods & Nutr, UGA
Gender and folate intake affect choline dynamics and gene expression in mice consuming isotopically labeled choline.
Authors: Jiang Xinyin , Chew Tina , Yan Jian , Wang Wei , Carrier Bradley , Lusa Amanda , West Allyson , Malysheva Olga , Caudill Marie A 
Published: June 2021

This study investigated the effects of folate intake, Mthfr deficiency, and gender on the fate of orally consumed choline and on the transcript levels of choline metabolizing genes. Mthfr +/+ or +/− mice (n=40; 20 nonpregnant female, 20 male; age 10 wk) were randomized to a folate sufficient or folate deficient diet for 8 wk during which modest amounts of labeled choline (d9‐choline; 1.6 mM), added to the drinking water, were consumed. Based on the concentrations of deuterium labeled choline metabolites in liver, gender robustly (P<0.01) affected choline flux. Compared to males, females had higher concentrations of d9‐phosphatidylcholine (PC, 1.5 times), d3‐PC (2 times), d9‐glycerophosphocholine (GPC, 4 times), d9‐betaine (2 times) and d6‐dimethylglycine (2 times). Female mice also expressed more PEMT in liver and kidney, more BHMT in kidney, and less BHMT in liver. Folate deficiency also influenced (P<0.05) choline dynamics in female mice with lower hepatic concentrations of d3‐PC and d9‐GPC. Increased expression (~3 times) of hepatic choline dehydrogenase and brain choline acetyltransferase was also observed in both genders. In contrast, Mthfr deficiency had subtle effects on choline metabolism; none of which achieved statistical significance. Taken together, these data show enhanced choline cycling and greater sensitivity to folate intake in nonpregnant female than male mice.Grant Funding Source: Funded in part by NIH Grant No. S06GM053933 and the California Agricultural Research Initiative
Oral betaine supplementation restores ATP concentrations in choline dehydrogenase knockout mouse spermatozoa
Authors: Johnson Amy Rose , Zeisel Steven 
Published: June 2021

Choline dehydrogenase (CHDH) converts choline to betaine, an important source of methyl groups for one‐carbon metabolism and an organic osmolyte. Deletion of the choline dehydrogenase gene in mice (Chdh−/−) leads to very low betaine concentrations in tissues, including testis, an organ that normally contains 10x more betaine than liver. Chdh−/− male mice are infertile due to diminished sperm motility that may be linked to the reduction of ATP in these cells. Feeding Chdh−/− male mice betaine via drinking water for the duration of one mouse spermatic cycle (42 days) increased testicular betaine concentrations and restored ATP concentrations to levels measured in Chdh+/+ and Chdh+/− spermatozoa (neither of which show impaired sperm motility or fertility). Sperm motility increased by 100% (from 15% progressive motility to 30% progressive motility), but was not fully restored to the level of Chdh+/+ and Chdh+/− mice (58% progressive motility) indicating that betaine plays an important role in sperm cell motility apart from normalizing ATP concentration, perhaps through its role as an osmolyte. Our data suggest that betaine is necessary for normal sperm cell function and men who carry functional mutations that decrease the activity of the CHDH enzyme may be more likely to have decreased fertility. This work is supported by grants from the NIH (AG09525, DK55865, DK56350). ARJ is supported by a scholarship from Balchem Corporation.Grant Funding Source: National Institutes of Health (AG09525, DK55865, DK56350)
Transcriptional Regulation of the Menkes Copper ATPase (Atp7a) Gene by Hypoxia Inducible Factor (HIF) During Iron Deficiency
Authors: Xie Liwei , Collins James F. 
Published: June 2021

Several intestinal genes are induced by HIF‐2α during iron deficiency, including divalent metal transporter 1 (Dmt1) and duodenal cytochrome B (DcytB). We previously observed that Atp7a was strongly upregulated in the duodenum of iron deficient rats. We thus sought to test the hypothesis that Atp7a is regulated by one of the HIFs during iron deprivation. To mimic hypoxia, rat intestinal epithelial (IEC‐6) cells were treated with CoCl2 or an iron chelator plus copper; both treatments led to induction of Atp7a mRNA expression. Cells were further exposed to low oxygen conditions, causing a ~4‐fold increase in Atp7a expression. To decipher the molecular mechanism of this induction, several Atp7a promoter fragments (ranging in size from 3000 to 50 bp) were PCR amplified and cloned into a firefly luciferase reporter vector. A 224 bp basal promoter fragment with full activity was identified, which contained evolutionarily conserved HIF binding sites. HIF‐1α and HIF‐2α over‐expression led to a significant increase in Atp7a promoter activity (2‐ and 4‐fold, respectively). Overall, this study demonstrates that Atp7a is regulated by HIF during iron deprivation, in parallel to other iron and copper related genes. Future experiments using chromatin immunoprecipitation (ChIP) and gel mobility shift assay are underway to determine precisely which HIF isoform (HIF‐1α or ‐2α) regulates Atp7a expression.Grant Funding Source: 1R01 DK074867
Dietary iron affects mRNA expression of porcine copper transporters
Authors: Fry Robert Scott , Spears Jerry W , Hansen Stephanie L , Ashwell Melissa S 
Published: June 2021

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