bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐throughput screening of natural products for NGF mimetic effects on neurite outgrowth in dopaminergic PC‐12 cells (727.5)
Authors: Georges Beatrice , Mazzio Elizabeth , Soliman Karam
Published: June 2021

The capacity of the human brain to enable growth of neurons occurs through neural stem cell differentiation guided by trophic factors such as brain‐derived neurotrophic factor or nerve growth factor (NGF). Elevated levels of NGF are believed to play a protective role in preventing a diverse range of age related neurodegenerative conditions. Moreover, PC‐12 dopaminergic cells are a valuable model for evaluating neuroprotective / trophic agents relevant to Parkinson's disease. In this study, we screened 1145 compounds [29 flavonoids, 168 synthetic drugs, 948 herb, fruit and vegetable extracts] for NGF mimetic effects in PC‐12 cells in the absence of NGF. The data indicate that 2 natural products of the 1145 tested at sub‐lethal concentrations had capacity to initiate neurite outgrowth comparable to NGF, which acquired properties of sympathetic neurons. Differentiation was analyzed by fluorescent immunocytochemistry Alexa (488)‐conjugated phalloidin / propidium iodide nuclear counterstain and contrast microscopy in live cells. These data support very unique properties of few natural products to mimic the effects of NGF.

Grant Funding Source: Supported by NIMHD G12 MD007582 and P20 MD006738
Bile acid sequestrants activate novel signaling pathways in the kidney and prevent obesity‐induced renal disease (767.10)
Authors: Luo Yuhuan , Wang Xiaoxin , Levi Moshe
Published: June 2021

Bile acid sequestrants (BAS) are orally administered nonabsorbable polymers that decrease serum cholesterol and serum glucose in patients and animal models with type 2 diabetes mellitus. The effects of BAS on renal dysfunction in obesity and insulin resistance or type 2 diabetes mellitus have not been studied. Our goal was to evaluate the effect of BAS on metabolic and renal parameters in diet induced obesity. Our studies were performed in C57BL/6J male mice fed a control low fat (LF) diet (10 kcal% fat) or high fat (HF) diet (60 kcal% fat). The diets were supplemented with a) no addition or b) 2% sevelamer a BAS. Treatment with BAS prevented HF diet induced body weight gain, improved fasting blood glucose and glucose tolerance, and prevented the increases in serum cholesterol as well as insulin and leptin levels in HF mice. BAS prevented the increase in urine albumin excretion and decreased the PAS staining in the kidney of HF mice. Treatment with BAS decreased the renal lipid accumulation as shown by oil red O staining. HF diet induced upregulation of profibrotic genes (TGF‐β, CTGF, and PAI‐1) and proinflammatory genes (MCP‐1, TLR2, and TLR4) in the kidney which were decreased by treatment with BAS. In addition BAS induced downregulation of extracellular matrix protein fibronectin and macrophage marker CD68 expression in the kidney. The beneficial effects of BAS were also associated with decreases in renal gluconeogenic gene expression (PEPCK and G6Pase) and renal glucose transporter (SGLT2). Treatment with BAS also and most notably increased renal expression of Nrf1, SIRT1, PGC‐1a,SIRT3, ERRa, that mediate mitochondrial biogenesis, MCAD and LCAD, that mediate fatty acid oxidation, and Nrf2, HO‐1, and SOD, that mediate anti‐oxidative stress. In summary, our study showed a novel renoprotective role for bile acid sequestrant treatment in mice with diet induced obesity, insulin and leptin resistance.

Grant Funding Source: NIH, VA, Genzyme, Daiichi Sankyo
p‐Aminosalicylic acid prevents the loss of immunofluorescence emissions of postsynaptic dopamine D2 receptors due to manganese treatment (796.1)
Authors: Chekayev Yelena , Loney‐Walsh Kurt , Carroll Margaret , Catapane Edward
Published: June 2021

Manganese (Mn) a neurotoxin causing Manganism, a Parkinsons‐like disease, disrupts dopamine (DA) neurons. The neurotoxic mechanism is not fully resolved. It’s postulated more related to dysfunction of DA D2 receptors than degeneration of DA neurons. Crassostrea virginica gill lateral cells are innervated by DA nerves and have D2 post‐synaptic receptors. Mn blocks cilio‐inhibition of DA. PAS (p‐aminosalicylic acid) blocks the effects of Mn. It’s questioned if Mn decreases the number of DA D2 receptors in brain. We used 1̊ antibodies against D2 receptors and FITC‐linked 2̊ antibodies to quantify DA D2 receptors to test if Mn decreases the number of receptors in gill of C. virginica and if PAS prevents the decrease. We treated animals with 500 µM of Mn for up to 6 days. Sections were viewed on a fluorescence microscope, intensity was quantified with ImageJ software. Control gills had bright fluorescence corresponding to lateral and other gill cells. Intensity from animals treated up to 6 days with Mn showed a decrease up to 36% of controls. Animals co‐treated with Mn and PAS did not show reduced fluorescence. The study shows negative correlation between fluorescence intensity of DA D2 receptors in Mn treated animals vs controls and PAS negates effects of Mn. Whether intensity loss is due to decrease in D2 receptor number or altering of protein conformation and ligand binding site of D2 receptors needs to be further explored.

Grant Funding Source: NIH‐ 2R25GM06003, NSF‐ 0622197, NYSED‐ 0516041071
Amphetamine exposure during development causes epigenetic trans‐generational changes in drug sensitivity in Caenorhabditis elegans (803.8)
Authors: McCowan Talus , Safratowich Bryan , Ohm Joyce , Carvelli Lucia
Published: June 2021

It’s well known that psychostimulants like amphetamine (AMPH) increase the amount of dopamine in the synaptic cleft. In C. elegans, it has been shown that a dopamine increase in the synapses causes a unique behavior named swimming induced paralysis (SWIP). Previous studies demonstrated that SWIP is a valid tool to investigate the effect of addictive drugs. Here, we explored the response to AMPH in C. elegans adult animals following previous exposure to the drug during development, as well as the second generation to see if a change in response was passed to progeny. Our results show that adult animals (F0) exposed to AMPH during development had a higher AMPH‐induced SWIP with respect to control‐exposed animals. Further, we found an elevated SWIP response in the second generation (F1) of animals originated from maternal lines that were exposed to AMPH during development. Epigenetic mechanisms were investigated to explain the inherited change in response to AMPH. Histone3 Lys4 trimethylation (H3K4me3) and histone3 Lys27 (H3K27me3) are promoter‐specific histone modifications associated with active transcription and gene repression, respectively. To test if H3K4 or H3K27 methylation were a contributing factor in the increased SWIP response seen after AMPH exposure, we performed western blot assays against H3K4me3 and H3K27me3 in protein samples collected from F0 and F1 animals. Our data shows that AMPH exposure during development decreases H3K4me3 expression in the F1 generation, while no change is seen in H3K27. These results suggest that epigenetic mechanisms underlie the trans‐generational effects induced by AMPH. Other epigenetic markers are currently under investigation.

Grant Funding Source: Supported by P20 GM104360‐1 NIH Grant
Knowledge of foodborne illnesses in people living with HIV in Miami (806.5)
Authors: Antoine Lovely , Campa Adriana , Martinez Sabrina , Luisi Sonya , Fleetwood Christina , Baum Marianna
Published: June 2021

Background: Food‐borne illnesses are more severe and fatal in HIV‐infected persons. This study field‐tested a questionnaire on food safety knowledge in HIV+ adults.

Methods: After consenting, 92 participants completed the questionnaire on food safety. The questionnaire included 12 mutually excluding knowledge questions. Passing score was >70% (or >9 correct questions out of a possible 12 points).

Results: Mean age was 41.1±17.1 years and 59% were male; 80.4% had insufficient scores on the questionnaire; 20.7% had no knowledge of the foodborne illnesses listed; 15.2% were able to identify at least one foodborne illness from the list; 64 % were able to identify two or more foodborne illnesses; and only 3.3% percent were able to identify all listed food‐borne illnesses. The question with the highest percentage of correct answers was on “frequent hand‐washing,” (91% correct answers) the most incorrect answers were on recognizing appropriate “defrosting process,” (10% with correct answers).

Conclusion: This study demonstrated the need to address the weak points revealed by the questionnaire and to develop educational programs that include Food Safety for this population at high risk of foodborne illnesses.

Grant Funding Source: Ronald E. McNair Post Baccalaureate
Is it time for father‐focused childhood obesity prevention programs for low‐income families? A needs assessment and feasibility study (808.19)
Authors: Mobley Amy , Adamsons Kari , Vollmer Rachel , Rose Andrew , Smith Jaime
Published: June 2021

Fathers (n=35) of children ages 3‐5 years old participated in focus groups (n=10) to determine 1) perceived key barriers and resources needed to improve nutrition and physical activity of their child, and 2) interest and feasibility of a father‐focused childhood obesity prevention program. Focus group questions were based on social cognitive theory. Each group was audio taped, transcribed verbatim and evaluated using thematic analysis. Participants were on average 36 ± 8 years old, 38% with high school or less education, 40% Hispanic, 38% black race, and 49% married. Key response themes indicated a need to improve: 1) self efficacy as it relates to cooking and increasing physical activity for their child, 2) behavioral capability in increasing their child’s vegetable and water consumption, and 3) problem solving as it relates to mealtime challenges and feeding practices. Fathers were generally interested in a program just for them. Based on focus group results, a father‐focused childhood obesity prevention program was piloted with father/child pairs (n=5) in a community setting over four interactive sessions. Topics focused on improving diet, cooking and, physical activity related self efficacy and skills. Qualitative program feedback was positive but future quantitative evaluation is needed to evaluate the impact on father/child health.

Grant Funding Source: University of Connecticut
Effects of childhood obesity prevention programs on blood pressure and lipids: a systematic review and meta‐analysis (808.25)
Authors: Cai Li , Wu Yang , Wilson Renee , Cheskin Lawrence , Kim Miyong , Wang Youfa
Published: June 2021

Aims: Assess effects of childhood obesity prevention programs on blood pressure (BP) and blood lipids in high‐income countries. Methods: We searched databases up to April 22, 2013 for intervention studies. Studies were included if they applied a diet and/or physical activity intervention(s) and were followed for 蠅1 y (or 蠅 6 months for school‐based interventions); excluded if targeted at only overweight/obese subjects or other patients. Results: We found 23 studies for BP and 17 for blood lipids, which overall showed desirable effects on BP and lipids. Pooled intervention effect was ‐1.64 mmHg (95% confidence interval (CI): ‐2.56, ‐0.71; P=0.001) for systolic BP, ‐1.44 mmHg (95% CI: ‐2.28, ‐0.60; P=0.001) for diastolic BP, ‐0.97 mg/dL (‐3.26, 1.32; P=0.408) for total cholesterol, ‐6.06 mg/dL (‐11.09, ‐1.02; P=0.018) for LDL‐C, 1.87 mg/dL (0.39, 3.34; P=0.013) for HDL‐C and ‐1.95 mg/dL (‐4.94, 1.04; P=0.202) for triglycerides. Thirteen interventions (46.4%) had a similar effect on both adiposity outcomes and BP; while 11 interventions (39.3%) showed a significant desirable effect on BP, but not on adiposity outcomes. Most of interventions (70%) had similar effects on adiposity outcomes and blood lipids. Conclusions: Obesity prevention programs have desirable effects on BP, LDL‐C and HDL‐C. Measuring BP and lipids is recommended to fully capture intervention program effects.

Grant Funding Source: Supported by AHRQ (Contract No.HHSA‐290‐2007‐10061‐I)
Consumption of energy drinks among U.S. adolescents and adults, 2007‐2010 (810.18)
Authors: Onufrak Steve , Zytnick Deena , Sohyun Park , Kumar Gayathri
Published: June 2021

Energy drinks (ED) typically contain large amounts of caffeine and added sugars but prevalence of ED intake is not well known. We assessed ED intake among Americans aged 蠅12 years using 24‐h dietary recall data from 2007‐2010 National Health and Nutrition Examination Survey and examined the relationship between ED consumption and sociodemographic, behavioral, and dietary characteristics. Overall, 1.8% of Americans reported consuming any ED on the recall day. ED intake was more common among males (2.6 % vs. 0.9%, p<0.0001) and younger people (ages 20‐39:3.2%, ages 12‐19: 2.5%, age 蠅40: 0.7%, p<0.0001). ED intake was more common among current smokers (3.0% vs. 1.3% for former and 1.2% for never, p=0.0008), heavy alcohol drinkers (>14 drinks/week for males; > 7 drinks/week for females) (2.8% vs. 1.6% among those drinking less or none, p=0.02), and those who reported any vigorous physical activity (2.7% vs. 1.4%, p<0.0001). Intake did not differ by education, race/ethnicity, income, weight status, moderate physical activity, or survey time period. Age and sex adjusted total daily caffeine and sugar intake was greater among ED consumers compared to non‐consumers (290.2 mg caffeine vs. 131.2 mg, p<0.0001; 171.0 g sugar vs. 119.9 g, p<0.0001). Although overall prevalence of ED intake on any given day is low, daily caffeine and sugar intake is significantly greater among ED consumers.
Insulin resistance and lipid profile in diabetic adults with depression (810.24)
Authors: Kim Wookyoung , Shin Dayeon , Song SuJin , Song Won O.
Published: June 2021

The interaction between depression and diabetes mellitus (DM) is of considerable interest. A few studies focused on the effect of depression on self‐management in DM patients. This study aimed to investigate the relationship between depression and clinical biomarkers related to complications in DM. We analyzed the National Health and Nutrition Examination Survey data with sampling weights (2007‐2010). The prevalence of depression was higher in adults with DM than in healthy subjects (47.8% vs. 33.2%, p<0.0001) and in women than in men (56.0% vs. 37.2%, p<0.0001), and were older than those without depression (59.1±0.8 vs. 55.2±0.7, p=0.0014). Compared to the adults with DM without depression, those with DM and depression had higher mean BMI (33.7±0.8 vs. 32.8±0.5, p =0.0019); lower diastolic blood pressure (70.0±1.1 vs. 69.2±2.2, p=0.0196); higher total cholesterol (191.7±3.9 vs. 181.5±3.5, p=0.0010) and LDL‐cholesterol (102.9±2.7 vs. 98.5±4.2, p=0.0859), and lower HDL‐cholesterol (44.9±1.0 vs. 47.7±1.0, p=0.0130) after age and gender were controlled; and higher serum insulin levels (20.9±2.8 vs. 15.0±1.3, P=0.0031) and HOMA‐IR (8.3±1.3 vs. 6.4±0.8, P=0.0512) when adjusted for age, gender, and BMI. DM adults with depression show higher risks for comorbidity such as hypertension and cardiovascular diseases than in DM adults without depression.
Obesity and lack of nutrition knowledge in Mexico urban areas (810.28)
Authors: Cuevas‐Nasu Lucia , Shamah Levy Teresa , Gaona‐Pineda Elsa , Rodríguez‐Ramírez Sonia , Gómez‐Acosta Luz
Published: June 2021

Objective: To estimate the overweight (OW) and obesity (OB) prevalence in Mexican urban areas population and its relationship with nutrition knowledge levels.

Methods: The present is a cross‐sectional, probabilistic and multi stage study, representative at Mexican urban population level, data was obtained from “Food consumption in Mexican population” study. OW and OB prevalence was estimated using the Body Mass Index according to WHO cutoff points. Population was categorized as follow: familiar feeding responsible (mothers of 14 years or younger individuals), teenagers (15‐19 y) and adults (20‐79 y). Percentages of the population with correct, basic and unclear nutrition knowledge were estimated, the topics were the body functions of proteins, carbohydrates, fats, vitamins, iron and calcium.

Results: Prevalence of OW + OB was 3.8%, 42% and 69% for individuals younger than 5, from 5 to 19 and 20 to 79 years old respectively. More than 65% of the population mentioned to know the food groups. 33% of the familiar feeding responsible ignored the fats and protein functions. For overall groups the fiber functions remain unclear. Regarding the vitamins and its functions there was basic or unclear knowledge; however about the calcium more than 90% of the individuals have a correct knowledge about its functions. More than 40% of the teenagers reported to ignore the iron functions in the body.

Conclusions: Results shows high OW and OB prevalence and deficient knowledge about nutrition topics. This could be a limiting factor for the population in order to identify healthy feeding options and therefore its consumption.

Grant Funding Source: Supported by Nestlé México
The association of sugar‐sweetened beverage intake during infancy with sugar‐sweetened beverage intake at six years of age (811.16)
Authors: Park Sohyun , Pan Liping , Sherry Bettylou , Li Ruowei
Published: June 2021

Sugar‐sweetened beverage (SSB) intake is associated with adverse health consequences including obesity and dental caries. Due to limited information on associations between SSB intake during infancy and intake of SSBs in childhood, we examined this question using longitudinal data for 1333 U.S. children from the 2005‐2007 Infant Feeding Practices Study II and the 2012 Follow‐up Study at 6 years of age. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) for associations of SSB intake during infancy with consuming SSBs 蠅1 time/day at 6 years old after controlling for baseline characteristics. Based on maternal report, one‐fifth of children consumed SSBs at least 1 time/day at 6 years. The adjusted odds of consuming SSBs at 6 years 蠅1 time/day was significantly (p<0.05) higher among infants with any SSB intake during infancy vs. none (aOR=2.22), SSB introduction at <6 months (aOR=2.01) or 蠅6 months (aOR=2.33) vs. never, and mean SSB intake between 10 and 12 months of age (aOR=2.72 for 1‐<2 times/week, and 2.57 for 蠅3 times/week, vs. none). SSB intake during infancy significantly increased the likelihood of consuming SSBs 蠅1 time/day at 6 years of age. Our findings suggest that infancy may be an important time for mothers to establish healthy beverage practices for their children and these findings can be used to inform intervention efforts to reduce SSB intake among children.
Perception of weight status in children and adolescents: findings from the National Health and Nutrition Examination Survey (NHANES) 2005‐2010 (811.3)
Authors: Sarafrazi Neda , Hughes Jeffery , Borrud Lori , Burt Vicki , Paulose Ryne
Published: June 2021

Weight misperception in children and adolescents may lead to unhealthy or excessive weight control practices among overweight, underweight or normal weight individuals. Accurate self‐perception of weight status has been linked to appropriate weight control behaviors in youth.

The objective of this study was to examine gender and racial/ethnic differences in prevalence of weight misperception among children and adolescents.

We used data from 4355 children and adolescents aged 8‐15 years who participated in NHANES 2005‐2010. Accuracy of weight perception status was determined by comparing self‐reported weight status (overweight, about right and underweight) to actual weight status based on measured height and weight. The weight misperception prevalence was estimated and compared among age, gender and race/ethnic groups.

Nearly, 29% of children and adolescents have misperception of their weight status. Weight misperception is more common among boys than girls and among children than adolescents. The prevalence of weight status misperception was lowest among non‐Hispanic white children and adolescents (26.5%) compared to non‐Hispanic black (33.4%) and Mexican‐American (33.3%) children and adolescents.

Current estimates of weight perception status in children and adolescent may be useful in developing obesity prevention programs and in promoting healthy weight control behaviors.
Association between dietary intake status and purpose of exercise in Korean adults (811.4)
Authors: Shin Yoonjin , Ju Minjeong , Kim Yangha
Published: June 2021

This study investigated the dietary behaviors and nutritional status according to purpose of exercise. A total of 214 subjects, 20 to 30 years of age, who visited fitness centers in Seoul were enrolled. Anthropometrics, exercise habits, nutritional knowledge, and eating behaviors were analyzed using a questionnaire. Nutritional status was assessed by the diet record method. The subjects were divided into two groups based on their purpose of exercise: increasing muscle (Muscle growth, n = 107) or losing body weight (Weight loss, n = 107). The Muscle growth group contained a higher percentage of men, whereas the Weight loss group contained a higher percentage of women. The Muscle growth group showed significantly higher scores of nutritional knowledge and eating behaviors compared to the Weight loss group. The Muscle growth group also had a significantly higher intake of energy and protein compared to the Weight loss group. In fact, the intake of energy in the Weight loss group was lower than the estimated energy requirement (EER) for both men and women subjects. The intake of protein in the Muscle growth group was twice as much as the recommended nutrient intake (RNI). In conclusion, those who exercised with the aim of increasing muscle took excess dietary protein and those who exercised with the aim of weight loss had a lower energy intake than the EER.

Grant Funding Source: This work was supported by the Brain Korea 21 plus project funding (No. 22A20130012143)
Large vegan sample reports less anxiety and stress than omnivores (823.3)
Authors: Beezhold Bonnie , Radnitz Cynthia , DiMatteo Julie
Published: June 2021

Studies investigating mood in vegetarian diets have yielded conflicting results, either demonstrating risk for mental disorders or mood protection. We examined mood and diet in a large community sample of adult vegans (n=227) and omnivores (n=221). Participants completed an online survey which included the Depression Anxiety Stress Scale‐21. The sample was mostly female (78%), so one‐way between‐groups ANCOVAs were conducted in both males and females to compare the effect of diet type on DASS scores, adjusting for age. Age had a significant relationship with DASS‐Anxiety and DASS‐Stress scores (ω2 < .06). There was a difference in mean DASS‐A scores in males, F(1,105)=8.89, p=.004, ω2=.08, with vegans reporting lower anxiety scores than omnivores (2.81±0.40 vs 5.74±1.0); a vegan diet (r=‐.311) and daily fruit and vegetable intake (r=‐.246) were inversely related to anxiety in males. There was also a difference in mean DASS‐S scores in females, F(1,380)=6.22, p=.013, ω2=.02, with vegans reporting lower stress scores than omnivores (8.14±0.47 vs 10.31±0.61); a vegan diet (r=‐.126) and plant omega‐3 intake (r=‐.158) were inversely related to stress in females. The apparent mood protection of a vegan diet may be gender‐specific.
Serum metabolic profile of the 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary tumor in obese Zucker rat model (824.1)
Authors: Hakkak Reza , Korourian Soheila , Pavliv Oleksanda , Melnyk Stepan
Published: June 2021

Obesity is epidemic and can effect the metabolic profile in animals and humans. Obesity is linked to breast cancer development. We reported that obesity significantly lower serum level of S‐adenosylmethionine (SAM) and lower methylation ratio compare to lean rats. We investigated the serum profile of tumor vs. non‐tumor rats for methylation cycle and oxidative stress metabolites using DMBA‐induced obese zucker rat. Twenty (20) six‐week‐old obese female Zucker rats were gavaged at age 50 days with 65 mg DMBA/kg body weight and were sacrificed 155 days later. Serum concentration of tumor and non‐tumor bearing rats were measured for oxidative stress and methylation cycle metabolites: SAM, S‐adenosylhomocysteine (SAH), Methionine, reduced glutathione (GSH), oxidized glutathione (GSSG), Cysteine and Cystine by using HPLC and LC‐MS. We found a significant (P=0.004) decrease of GSH/GSSG ratio and significant (P=0.022) increase of Cystine/Cysteine ratio in tumor bearing rats. Despite a slight increase in concentration of free GSH and free Cysteine serum concentration also we found a significant higher (P=0.014) concentration of Methionine and SAM (P=0.038) in non‐tumor rats. Our results suggest that tumor bearing rats has higher level of oxidative stress which can affect methylation capacities of tumor bearing rats by decreasing concentration of amino acid Methionine and SAM concentration.

Grant Funding Source: Arkansas Bioscience Inst
Relationships between dietary intakes of choline and betaine, genetic polymorphisms of one‐carbon enzymes and tumour progression of patients with hepatocellular carcinoma (825.1)
Authors: Huang Kuang‐Ta , Kuo Chang‐Sheng , Huang Chi‐Yun , Kuo Hsing‐Tao , Cheng Chin‐Pao , Chen Chien‐Hung , Syu Huang Rwei‐Fen
Published: June 2021

Previous studies have demonstrated that choline deficiency preceded the formation of adenomas and hepatocellular carcinoma (HCC). Whether dietary intake of one‐carbon nutrients in particular for choline and betaine, risk factors for HCC development, may influence tumour progression was not known. The aims of the study were to investigate the relationships between these two dietary factors, genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and HCC progression. The study included 232 HCC patients with 63 individuals collected for dietary intake data. The database in NAHSIT (Taiwan food data bank) did not contain choline and betaine content values. The hypothetical choline and betaine food composition databases were constructed using the various versions of data sets from US Department of Agriculture (USDA) data sets, by matching identical foods from the NAHSIT database to the USDA database to assign choline and betaine values. The data showed that mean dietary choline intake of HCC patients was lower than the AI value for Taiwanese adults. Dietary betaine intake was inversely correlated with HCC tumor size (r = ‐0.30, p = 0.01) and tumor numbers (r = ‐0.24, p = 0.04). Combining with MTHFR genotype and other dietary one‐carbon factors, HCC patients who carried MTHFR 677 CT/TT genotype had lower lymphocytic mitochondrial DNA large deletion (p= 0.001, p= 0.001) when they got higher choline and betaine from their diet. In summary, dietary choline and betaine intakes were associated with HCC progressive markers, polymorphic or genetic damage markers among HCC patients. The mechanisms require further studies.
Nutritional status of paediatric cancer patients from the UK: a prospective cohort study (825.7)
Authors: Revuelta Iniesta Raquel , Jane McKenzie , Ilenia Paciarotti , Mark Brougham , David Wilson
Published: June 2021

Aim: To investigate the prevalence of malnutrition, patterns of change in nutritional status (NS) and potential factors which may contribute to the development of malnutrition in newly diagnosed Scottish paediatric cancer patients.

Methods: NS was assessed between Aug 2010‐Oct 2013 using anthropometry, body composition and dietary assessment. The primary outcome was malnutrition defined as body mass index (BMI) according to UK guidelines. Frisancho’s (1981) reference was used for arm anthropometry and to estimate muscle (FFM) and fat mass (FM). Correlations and multilevel analysis were performed.

Results: 74 (78%) patients were recruited. At baseline, the prevalence of undernutrition was 9.5%, overnutrition 5% and obesity 11%. Triceps skinfold identified the highest prevalence of undernutrition 13.5% and the lowest of obesity 1%. BMI [p=0.03; 95% CI (‐17 to ‐12)] and FM [p<0.05; 95% CI (677‐1122)] significantly increased after 3 months and remained steady thereafter, whilst FFM [p<0.001; 95% CI (2992‐3550)] significantly decreased during the first year. Only energy intake showed minor correlation with BMI (r=0.1; p=0.04) and TSF (r=0.2; p=0.03) at baseline.

Conclusion: Undernutrition was more prevalent at diagnosis, yet overnutrition increased significantly during treatment. The changes seen in body composition emphasise the need to implement new strategies to improve the NS of paediatric cancer patients.

Grant Funding Source: Fergus maclay Leukaemia Trust, Queen Margaret University and Leukaemia and Cancer Research Fund
Potential of a defatted green microalgal biomass as an iron source for hemoglobin repletion (828.8)
Authors: Kim Jonggun , Lei Xin Gen
Published: June 2021

Iron deficiency anemia is a widespread nutritional disorder around the world, and pigs are an excellent model to study human iron nutrition. Previous research in our laboratory demonstrated a tendency of feeding iron‐rich microalgae to elevate blood hemoglobin concentrations in pigs fed iron‐adequate diets. Two experiments were conducted in weanling pigs to determine such effectiveness of a defatted green microalgal biomass (Desmodesmus sp., Cellana, Kailua‐Kona, HI) generated from the biofuel research. In Experiment 1, pigs (11.3 ± 0.6 kg of body weight) with low hemoglobin concentrations (8.2 ± 2.9 g/dL) were fed a corn‐soy basal diet (BD) without supplemental iron (n = 5) or the diet plus 7.5% microalgae (n = 6) for 5 wk. The algae diet elevated (P < 0.05) packed cell volume by 23‐26% and blood hemoglobin concentrations by 22‐32% at or after wk 3. In Experiment 2, pigs (12.9 ± 0.6 kg) with normal blood hemoglobin concentrations (12.1 ± 0.38 g/dL) were fed the BD supplemented with ferrous sulfate (n = 10) or 15% algae (n = 10) for 5 wk. There was no dietary treatment effect on either packed cell volume or hemoglobin concentrations. The diets did not alter body weight gain or daily feed intake of pigs in either experiment. In conclusion, the defatted green microalgal biomass was effective in helping hemoglobin repletion of marginally anemic pigs. Our ongoing research is exploring novel promoting mechanisms of the biomass in addition to its high iron concentration.

Grant Funding Source: Supported in part by a USDA/DOE Biomass R&D Initiative grant (2010‐0106)
Dose response of aged garlic extract in streptozotocin ‐induced diabetic rats (829.9)
Authors: Thomson Martha , Al‐Qattan Khaled , J.S. Divya , Ali Muslim
Published: June 2021

The anti‐diabetic and antioxidant effects of 3 doses of aged garlic extract (AGE) were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin (STZ) and a fasting blood sugar >300 mg/dl indicated diabetes. AGE (Wakunaga‐Kyolic, USA) was administered at 3 different doses intraperitoneally (IP) – 600, 300 and 100 mg/kg ‐ daily for 8 weeks. Diabetic rats were divided into 5 groups; control, boiled AGE‐treated and the 3 AGE‐treated groups. A normal control group was also included. Effects in AGE‐treated diabetic rats were dose dependent. STZ‐induced diabetic rats lost significant weight during the experiment with AGE‐treated rats (600 and 300 mg/kg doses) maintaining their initial weights. Blood glucose as well as serum cholesterol and triglycerides were significantly elevated in diabetic rats, and lowered by AGE treatment. Serum insulin level was decreased over 10‐fold in diabetic rats and increased by AGE treatment; while erythrocyte glycated hemoglobin (GHb) increased over 3‐fold in diabetic rats with a marked decrease in AGE‐treated diabetic rats. Total antioxidant levels and catalase activity decreased (45‐70%) in serum, kidneys and livers of diabetic rats with significant recovery in AGE‐treated animals. In contrast, lipid peroxidation (MDA levels) increased in kidneys and livers of diabetic rats and was lowered in AGE‐treated diabetic rats. In general, administration of boiled AGE had few beneficial effects compared to AGE. Thus, AGE exhibits a dose‐dependent effect in ameliorating oxidative stress and other indicators of diabetes in STZ‐induced diabetic rats. The study was supported by KU grant #SL 02/13.

Grant Funding Source: Supported by Kuwait University SL 02/13
Chondroprotective role of whole grape polyphenols in stimulated SW 1353 cells (830.27)
Authors: Lucero Jacquelynn , Vijayagopal Parakat , Juma Shanil
Published: June 2021

In aging, increases in oxidative stress and inflammation cause an imbalance in the metabolic activity of chondrocytes leading to onset and progression of osteoarthritis. Resveratrol, a polyphenol rich in grapes has shown to inhibit chondrocyte apoptosis and suppress cyclooxygenase (COX‐2). Our study investigated the effect of whole grape polyphenols on cartilage cell integrity and markers of cartilage health using SW 1353 human chondrosarcoma cells that are compatible to primary chondrocytes. Whole grape polyphenols (WGP) were extracted from grape powder and concentrations were determined using Folin‐Calteau assay. For all experiments, cells treated with WGP were stimulated with the inflammatory compound, tert‐butyl hydroperoxide (tbHP). Cell proliferation significantly (p<.05) increased in a dose dependent manner with WGP at 20ug/ml (147% vs. Control). Cartilage degradation as indicated by glycoprotein‐39 (YKL‐40) levels was significantly lower with the three highest doses of WGP in comparison to control and tbHP stimulated cells. Toluidine blue and Safarin O staining indicated increase presence of type II collagen and proteoglycan in WGP treated cells. Using In‐Cell colorimetric ELISA, we did not observe a significant effect on COX‐2 protein expression with any WGP doses. Elucidation of mechanisms by which WGP protect cartilage cell destruction in presence of an inflammatory agent are warranted.

Grant Funding Source: Supported by California Table Grape Commission
Pulmonary expression and regulation of Cldn6 by tobacco smoke (834.3)
Authors: Jimenez Felix , Lewis Josh , Belgique Samuel , Wood Tyler , Reynolds Paul
Published: June 2021

Smoking is a major risk factor for several chronic diseases including chronic obstructive pulmonary disease (COPD), a condition involving both emphysema and inflammation of the airways. COPD severity directly relates to abnormalities of pulmonary epithelial cells. Claudins contribute to tight junctions that prevent paracellular transport of extracellular fluid and diverse substances and Claudin 6 (Cldn6) is a protein expressed prominently in the lung parenchyma. To determine whether Cldn6 was differentially influenced by tobacco smoke, Cldn6 was evaluated by q‐PCR, immunoblitting, and immunofluorescence following exposure to tobacco smoke. Q‐PCR and immunoblotting revealed that Cldn6 was increased in alveolar type II‐like epithelial cells (A549) but not in Bease2B cells, a cell line derived from proximal airway epithelium. Luciferase assays incorporating 0.5kb, 1.0kb, or 2.0kb of the Cldn6 promoter also revealed increased transcription of the gene when cells were exposed to cigarette smoke extract. Cldn6 was also markedly increased in the lungs of Balb/C mice exposed to tobacco smoke delivered by an automated smoke machine (InExpose, Scireq, Canada) compared to animals exposed to room air. These data reveal for the first time that tight junctional proteins are differentially regulated by tobacco smoke exposure and that Cldns are potentially involved as neighboring epithelial cells respond to tobacco smoke. Further research may show that complexes between cells contribute to impaired structural integrity of the lung coincident with smoking.

Grant Funding Source: Supported by the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU MEG Award (PRR).
Cytokine targets in the brain: impact on neurotransmitters and neurocircuits (84.4)
Authors: Miller Andrew
Published: June 2021

Activation of the immune system and release of cytokines can lead to behavioral changes. Given the association of immune activation with medical illness as well as psychological stress, such cytokine‐induced behavioral changes may contribute to the high rate of depression, anxiety and other behavioral alterations observed in the medically ill and the chronically stressed. Using the anti‐viral cytokine, interferon‐alpha, our group and others have demonstrated that cytokines can access the brain and alter the function of the basal ganglia as measured by functional magnetic resonance imaging and positron emission tomography. Cytokine‐induced alterations in basal ganglia function in turn have been associated with motor slowing, anhedonia and fatigue and appear to be mediated by alterations in dopamine metabolism. Cytokines also appear to activate brain areas including the dorsal anterior cingulate cortex that are associated with anxiety, arousal and alarm. Together, these cytokine effects on behavior may subserve evolutionary survival priorities during infection and/or wounding to conserve energy to fight pathogens and heal wounds while at the same time increasing vigilance against attack. Chronic activation of these brain circuits during illness or stress, however, may lead to behavioral pathologies in vulnerable individuals, which may be uniquely treated by therapies targeting the immune system.
Renal endoplasmic reticulum stress is induced via endothelin A receptor activation (857.7)
Authors: De Miguel Carmen , Hobbs Janet , Pollock David , Pollock Jennifer
Published: June 2021

The endothelin (ET‐1) system has been recently implicated in renal endoplasmic reticulum (ER) stress development, a type of cellular stress caused by misfolded protein accumulation within this organelle. To clarify the role of the ETA receptor in renal ER stress, we hypothesized that pharmacological blockade of this receptor via ABT‐627 leads to reduced renal response to the ER stress inducer tunicamycin (TM). WT and ETB deficient (sl/sl) rats (n=3‐4/group) were pre‐treated with ABT‐627 (5mg/kg/day; drinking water) for 1 week and given a single injection of TM (2ug/g bwt; i.p.). Kidneys, plasma and urine were collected 24h later. ER stress markers in renal cortical and medullary regions were determined by qRT‐PCR. Treatment of WT animals with ABT‐627 significantly reduced the ER stress response to TM in cortex and outer medulla (fold change/WT+H2O; GRP78 (0.12±0.02 and 0.04± 0.01, respectively), ATF‐4 (0.20± 0.02 and 0.15± 0.02), ATF‐6 (0.28± 0.08 and 0.18± 0.04), spliced XBP‐1 (0.03+0.01 and 0.05± 0.01) and CHOP (0.02± 0.01 and 0.04± 0.01). On the contrary, ABT‐627 pre‐treatment failed to decrease cortical and medullary ER stress development in sl/sl rats. These results indicate that ETA receptor activation leads to induction of renal ER stress genes, while ETB receptor activation has protective effects. Modulation of the ET system may have therapeutic value in protecting against ER stress‐induced renal injury.

Grant Funding Source: Supported by NIH and AHA
Relationship between muscle stiffness and strength in older adults: implications for the development of sarcopenia (863.2)
Authors: Hibbert Jamie , Domire Zachary
Published: June 2021

Introduction: It has been shown that older adults have an attenuated hypertrophic response to exercise as compared to young adults. One possible explanation for this response is decreased mechanotransduction into the myocytes due to stiffening of the extracellular matrix with the aging process; thus muscle cells will experience less strain and therefore less mechanical signaling for any applied force. We hypothesize that muscle stiffness decreases response to exercise, and that there is an inverse relationship between strength and muscle stiffness. This would indicate that muscle stiffening plays a role in the development of sarcopenia.

Objective: The purpose of this study is to determine the relationship between muscle stiffness and strength in older adults.

Methods: Data on muscle stiffness and strength were collected for 19 healthy women (age 70‐80). Stiffness measurements were taken of the Vastus Lateralis using ultrasound elastography (SuperSonic Imagine). Maximal strength was measured using a HUMAC isokinetic dynamometer.

Results: Two subjects were excluded for lack of effort during strength testing. There was a moderate correlation (r=‐0.36) between strength and muscle stiffness. There was no relationship (r=‐0.2) between strength and age.

Conclusions: This supports the hypothesis that muscle stiffness contributes to decreased response to exercise and the development of sarcopenia.
Endochondral bone tissue engineering: using cartilage to drive vascularized bone regeneration (87.6)
Authors: Bahney Chelsea , Jha Amit , Hu Diane , Taylor Aaron , Britz Hayley , Hallgrimsson Benedikt , Miclau Ted , Marcucio Ralph
Published: June 2021

There is a significant unmet clinical need to develop improved strategies to promote vascularized bone regeneration. Current bone graft technologies promote repair through direct osteogenesis by use of auto‐ or allografted bone. Critical failures associated with these therapies include osteonecrosis and poor osseointegration. The long‐term goal of this project is to develop a tissue engineering approach to promote endochondral bone formation, in which bone forms through a cartilage intermediate. Endochondral ossification is the normal mechanism by which long bones form and the majority of fractures heal. By leveraging this normal healing response, we hypothesize we can overcome the clinical problems of osteonecrosis and poor integration to produce a vascularized and integrated bone regenerate. To test this hypothesis, critical sized defects were created in mid‐diaphysis of murine tibia. Defects remained empty, or were filled with a cartilage graft, autograft or allograft bone. Our data show cartilage grafts effectively transformed into vascularized bone and integrated with the host bone to perform statistically better than allografts and equivalent to autografts. To translate this therapy we have developed a biomimetic acrylated hyaluronic acid hydrogel that contains peptide sequences for cell attachment (bone sialoprotein‐derived RGD), heparin for modulation and sequestration of growth factors, and enzymatically degradable MMP‐13 crosslinks. Hypertrophic chondrocytes encapsulated in these scaffolds mineralization during in vitro culture in basal medium. In ongoing work, these scaffolds have been transplanted into a subcutaneous model of osteonecrosis to evaluate the capacity to re‐vitalize bone. This novel approach to bone tissue engineering has the potential to improve clinical outcomes in bone regeneration.

Grant Funding Source: Supported by NIH 5F32AR062469 (CSB), MTF Junior Investigator Award (CSB), UCSF CTSI Award (CSB)
In vitro airway responses to methacholine challenge following intermittent neonatal CPAP in mice (870.5)
Authors: Mayer Catherine , Reyburn Brent , Martin Richard , MacFarlane Peter
Published: June 2021

Although continuous positive airway pressure (CPAP) is commonly used in the care of pre‐term infants, its long‐term effects on airway reactivity are largely unknown. In the current study, we investigated whether neonatal CPAP leads to long‐term changes in airway responses to methacholine using the in vitro mouse lung slice preparation. We hypothesized that CPAP treatment during the first week of life would result in a long‐term decrease in airway responsiveness to methacholine. Neonatal mice were exposed to CPAP (6cm H2O) for 3 hours per day for the first 7 postnatal days. Control animals experienced the same conditions as experimental animals only with no CPAP. On days 7 and 21 (2 weeks after CPAP), precision cut lung slices were harvested, and airway responses to increasing doses of methacholine (0.25µM‐8µM) were examined. Contrary to our hypothesis, at both P7 and P21, airways from CPAP exposed mice displayed increased airway reactivity to methacholine challenge when compared to airways from age‐matched control mice. We concluded that CPAP treatment during the early neonatal period may lead to a long‐term increase in airway reactivity.
Intrathecal BDNF acutely enhances rhythmic phrenic activity after cervical spinal cord injury in rats (871.3)
Authors: Mantilla Carlos , Zhan Wen‐Zhi , Ermilov Leonid , Sieck Gary
Published: June 2021

Upper cervical spinal cord injury (SCI) disrupts descending inspiratory‐related drive to phrenic motoneurons paralyzing the diaphragm muscle. Over time following unilateral C2 hemisection (SH), there is gradual recovery of rhythmic diaphragm activity ipsilaterally, consistent with neuroplasticity. We recently reported that functional recovery after SH is enhanced by chronic intrathecal delivery of BDNF to the region of the phrenic motor neuron pool. BDNF also exerts acute effects on synaptic transmission that may enhance functional recovery. Accordingly, we hypothesized that intrathecal delivery of BDNF to the phrenic motor neuron pool acutely enhances functional recovery post‐SH. Rats were implanted with diaphragm electrodes for chronic EMG recordings post‐SH, verifying absence of ipsilateral eupneic diaphragm EMG activity by 3 and 28 days after SH. In spontaneously breathing, anesthetized animals, BDNF was administered intrathecally (30 μl) at C4 and ipsilateral rhythmic diaphragm EMG activity was restored (~120% of pre‐injury diaphragm root‐mean‐square [RMS] EMG amplitude) within ~30 min of administration. Diaphragm RMS EMG increased further following exposure to hypoxia (10% O2)‐hypercapnia (5% CO2) and intranasal capsaicin. These results highlight the acute role of BDNF signaling in the phrenic motor neuron pool in chronically‐injured rats displaying no spontaneous recovery.

Grant Funding Source: Supported by NIH grant R01 HL096750.
Angiotensin‐II promotes ACE2 shedding by increasing ADAM17 expression and oxidative stress in Neuro2A cells (874.10)
Authors: Moreira de Queiroz Thyago , Sriramula Srinivas , Chaudhari Anju , Filipeanu Catalin , Lazartigues Eric
Published: June 2021

Decrease of Angiotensin‐converting enzyme 2 (ACE2) expression and activity in the brain has been shown to be associated with neurogenic hypertension. We recently reported that up‐regulation of the matrix metalloprotease A Disintegrin And Metalloprotease 17 (ADAM17) expression in hypertension mediates ACE2 shedding in neurons. To study the contribution of Ang II Type 1 Receptor (AT1R) and oxidative stress on ACE2 shedding, Neuro2A (neuronal cell line) were first transfected with human ACE2 (hACE2) then pretreated with AT1R blocker Losartan (10 µM) or the reactive oxygen species scavenger Tempol (10 µM), 30 min prior to treatment with AngII (100 and 300 nM). Western blotting revealed that ACE2 expression was decreased (12 and 40%, respectively), while ADAM17 expression was increased (30 and 36%, respectively) in Neuro2A cells after Ang II treatment. Pretreatment with losartan or tempol attenuated the effect of Ang II on ADAM17 expression (18 and 19%, respectively). To further study the involvement of oxidative stress in Ang II‐induced ADAM17 expression, another set of Neuro2A cells were studied without transfection with hACE2. In these cells treated with Ang II (100 nM), ADAM17 expression was similarly decreased by tempol. These data suggest that ADAM17 expression is increased by an AT1R‐dependent, as well as oxidative stress‐dependent mechanism, leading to enhanced ACE2 shedding in neurons.

Grant Funding Source: Supported by AHA 12EIA8030004, CNPq