bluuebunny/crossref_metadata_2025 huggingface dataset:
Level of Interest in a Weight Management Program Among Adult US Military Dependents
Authors: Bukhari Asma Sultana , Young Andrew J. , McGraw Susan M. , Roberts Susan B. , Das Sai Krupa
Published: June 2021

There is little information on the extent to which different challenged populations with high rates of overweight and obesity have interest in participating in weight management programs. The purpose of this study was to indentify potential rates of enrollment in a weight management program among adult US military dependants. We conducted a cross‐sectional survey in adult dependants (N=198; mean ±SD, age =34±8 years, BMI =25.5±5.5 kg/m2) of US active duty military personnel (ADMP). Responses to a self‐administered questionnaire on demographics and level of interest in a weight management program were assessed. Of the respondents 93% were female and 7% were male; 45% of the dependant's ADMP were officers and 55% were enlisted. There was a strong effect of current weight status on interest in participation, with 71% of obese individuals, 54% of overweight and only 10% of underweight “very likely” to participate (χ2=6.737, p<0.05).

BMI (kg/m2)
N=195 N (%)
Likelihood to Participate by BMI Category

Very Likely (%)
Moderately Likely (%)
Not Likely (%)

<18.5
10 (5)
10
30
60

18.5 – 24.9
93 (48)
38
39
23

25–29.9
54 (28)
54
32
15

≥ 30
38 (20)
71
26
3

These data suggest that there is widespread interest in participation in a weight management program among adult dependents of ADMP who are overweight or obese.
Differential effects of fructose on glycemic control: A systematic review and meta‐analysis of controlled feeding trials
Authors: Cozma Adrian I , de Souza Russell J , Chiavaroli Laura , Ha Vanessa , Mirrahimi Arash , Beyene Joseph , Kendall Cyril WC , Jenkins David JA , Sievenpiper John L
Published: June 2021

Objective

Fructose has become a focus of concern. To assess the effect of fructose on glycemic control, we conducted a systematic review and meta‐analysis.

Methods

We searched MEDLINE, EMBASE, and Cochrane Library (up to Nov 5, 2012) for relevant controlled trials ≥7‐days. Two independent reviewers extracted data. Data were pooled using random effects models for glycated blood proteins (GBP) and fasting glucose (FG) and insulin (FI).

Results

Eligibility criteria were met by 47 isocaloric trials (n=863), in which fructose was exchanged isocalorically for other carbohydrate, and 12 hypercaloric trials (n=143), in which the diet was supplemented with excess energy from fructose. Fructose in isocaloric trials reduced GBP (standardized mean difference = − 0.29 [95% CI: −0.46, −0.11]), equivalent to a ~0.59% reduction in HbA1c, in people with and without diabetes. In contrast, fructose in hypercaloric trials increased FG (mean difference [MD] = 0.18 mmol/L [95% CI: 0.08, 0.29]) and FI (MD = 6.06 pmol/L [95% CI: 3.70, 8.31]).

Limitations

Most trials were small, short, and of poor quality.

Conclusions

Isocaloric exchange of fructose for other carbohydrate improves glycemic control in people with and without diabetes. Fructose providing excess energy, however, raises fasting glucose and insulin levels, an effect that may be more owing to excess energy than fructose.

Funding: Canadian Institutes of Health Research.

Grant Funding Source: CIHR
Self‐identified race, gender and their anthropometric correlates of cardiometabolic risk among healthy university students
Authors: Nichols Selby SD , Dalrymple Nequesha
Published: June 2021

In this study we investigated the race and gender associated anthropometric correlates of cardiometabolic risk among disease free University students. Participation was voluntary. Participants had blood pressure, anthropometry, and fasting blood lipids and sugars measured using standard procedures.

Results

318 persons participated in the study including (African descent (A) =156; East Indian descent=93; Mixed descent=69). Participants of African descent had significantly higher HDL – cholesterol than their East Indian counterparts. Females of African descent were also more likely to have HDL‐cholesterol less than 50mg/dl and elevated total cholesterol to HDL‐cholesterol ratio greater than their mixed descent counterparts (62% vs. 36%; p=0.03).Males of African descent were significantly likely than their mixed descent counterparts to have BMI>;30 (18% vs. 4%) while males of African descent were more likely than their East Indian counterparts to have elevated SBP. Males had significantly lower mean HDL than their female counterparts. Waist circumference, BMI, percentage body fat and waist/height ratio were all positive correlated to an increased risk for metabolic syndrome (i.e. having three or more cardiometabolic risk factors.

Conclusion

Our findings suggest strong associations among anthropometric variables and cardiometabolic risk factor level that were gender and race specific.
Antioxidant effect of myricetin in animal model of type 2 diabetes
Authors: Choi Ha‐Neul , Kang Min‐Jung , Kim Jung‐In
Published: June 2021

Hyperglycemia increases oxidative stress which contributes to the development of diabetic complications. Myricetin has been reported to show antioxidant activity in vitro. The purpose of this study was to investigate the antioxidant effect of myricetin in animal model of type 2 diabetes. Four‐week‐old male db/db mice were fed AIN‐93G diet or diet containing myricetin (150 mg/kg) for 7 weeks after one week of adaptation. The animals were sacrificed after an overnight‐fast. Thiobarbituric acid reactive substances (TBARS) levels of the liver were measured. Activities of hepatic antioxidant enzymes were measured. Hepatic TBARS levels were significantly reduced by consumption of myricetin in db/db mice. Activities of superoxide dismutase (SOD) and catalase of myricetin group were significantly higher than those of the control group (p<0.05). Consumption of myricetin significantly increased glutathione peroxidase (GSH‐Px) activities compared with the control group. These results indicate that myricetin exerts antioxidant effect in db/db mice, suggesting it could be useful in preventing diabetic complications. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012015763).
Adipokines and Cytokines in Overweight and Obese Adolescents: Effect of interventions on Physical Activity and Nutrition Education
Authors: Martinez‐Carillo Beatriz Elina , Valdés‐Ramos Roxana , Tlatempa‐Sotelo Patricia , Guadarrama‐Lopez Ana Laura , Oros‐Pantoja Rigoberto , Alcaraz Citlalli
Published: June 2021

To identify the effect of physical activity and nutrition education on the metabolic profile of Mexican adolescents, we designed a 6 month intervention in schools from the cities of Toluca and Tuxtla. Three schools from each site were randomly assigned to a daily 60‐minute physical activity program (PA), a daily one‐hour nutrition education session (NE) or a combination of both (PA‐NE). After informed consent from parents and assent from adolescents, 30 overweight or obese subjects from each school were included in the program. Anthropometric (weight and height for BMI and waist circumference) and biochemical (Adiponectin, Resistin, Interferon ã, Interleukins 2, 6 and 8) evaluations were undertaken by trained personnel before and after the 6‐month period. Repeated measurements ANOVA showed significant differences by study site in Resistin (F=49.36, p<0.001), Adiponectin (F=315.52, p<0.001), IL‐2 (F=3.93, p<0.05) and IL‐8 (F=98.39, p<0.001); by intervention group in IL‐2 (F=4.08, p<0.05), and IL‐8 (F=24.63, p<0.001) and by gender in Resistin (F=5.3, p<0.05). BMI values were maintained or increased, while waist circumference decreased in the majority of cases. However, we observed decreases in adipokines and increases in proinflammatory cytokines indicating a need to evaluate more closely the metabolic effect of intervention programs and not only the gross anthropometric changes.
Caffeine Increases Liking and Consumption of Novel Flavored Yogurt
Authors: Panek Leah M , Swoboda Christine , Bendlin Ashley , Temple Jennifer L
Published: June 2021

The purpose of the current experiment was to test the hypothesis that a caffeinated beverage paired with a novel flavored yogurt will increase preference for that yogurt compared to one paired with placebo and, that liking would increase more when caffeine was paired with high energy density (HED) yogurt. Men and women (n=68) were randomized to receive a beverage containing placebo (PLA) or caffeine (CAF) and to consume a low (LED) or HED, novel flavored yogurt. Participants rated, ranked, and consumed seven novel flavored yogurts and then had a target yogurt paired with either PLA or CAF over four consecutive days. In general, yogurt liking increased over time, the HED yogurt was liked more than the LED yogurt and yogurt paired with caffeine was liked more than yogurt paired with placebo. Participants showed a significant increase in liking of LED yogurt paired with caffeine compared to those with LED yogurt paired with placebo. Caffeine administration may increase liking and consumption of novel flavored foods, particularly if the food is not highly liked at baseline. This suggests that caffeine‐pairing may be a way to increase liking of LED foods, such as vegetables and fruit.

This study was funded through funds to JLT from the University at Buffalo
Organic mineral levels in the first 96‐hours post‐hatch impact performance and intestinal gene expression in broiler chicks
Authors: Brennan Kristen M , Graugnard Daniel E , Samuel Ryan S , Spangler Leya , Ao Tuoying , Pescatore Anthony J
Published: June 2021

A study was conducted to determine the effect of post‐hatch (0–96 h) organic mineral (Cu, Zn, Mn) levels on intestinal gene expression profiles in broilers. Chicks were randomly assigned to one of two treatment groups: corn‐soy diet with organic Zn, Cu, Mn (Bioplex®, Alltech Inc.) at 100% (control, C) or 20% (low, L) of NRC requirements. After 96 h, 7 birds from each group were euthanized and jejunal gene expression was measured using Affymetrix Chicken Genome Array. Body weight, ADG and FCR did not differ between treatments at d 5. Overall 749 genes (432 up‐regulated; 317 down‐regulated) were differentially expressed in L vs C birds. Ingenuity pathway analysis indicated that the top biological functions with positive activation (z‐score >; 2) in L birds were related to molecular transport, nucleic acid metabolism, immune cell trafficking, lipid metabolism and cellular movement. Pathways associated with cell signaling (e.g., integrin‐linked kinase and Wnt/â‐catenin) and pathways related to cell growth and vascular homeostasis (sphingosine‐1‐phosphate and endothelin, respectively) were significantly activated by L compared with C. Gene expression profiles indicate that feeding broilers low concentrations of organic minerals in the first 96 h post‐hatch activates pathways and functions that aid in the development of the intestine.
Evaluation of Anti‐Diabetic Potential of a Novel Soluble Silicate in Rodent Models
Authors: Vattem Dhiraj Anil , Maitin Vatsala , Richardson Charles Reed
Published: June 2021

Emerging research suggests that they may have micronutrient and health promoting functions. However, their mechanism of action is not clearly understood. We have previously shown that one species of soluble silicate [Na8.2Si4.4H9.7O17.6] has antioxidant properties and can modulate gene function relevant to metabolic regulation. Here we present results from an in vivo evaluation of this silicate species on progression and management of diabetes in rodent models. Co‐supplementation of silicates at dosage of 3.5mM with metformin (250–1000 mg) on diabetic and cardiovascular parameters was evaluated in ZDF‐Leprfa/Crl male rats and BKS.Cg‐m +/+ Leprdb/J mouse for 6–18 weeks. Our results indicate that with a moderately high staring glucose (300–400 mg/dl) co‐treatment of 3.5mM with 500 mg metformin had a significant effect on reduction of blood glucose, HbA1c, cholesterol, triglyceride and body weight after 8–11 weeks of treatment and was associated with lower incidences of cataracts. There was also a significant improvement in liver function as indicated by lower AST and ALT levels. Gross necroscopy indicated no abnormality in liver and kidneys. Results suggest a potential anti‐diabetic function of [Na8.2Si4.4H9.7O17.6], further investigation is necessary to understand mechanism of action.
Methylseleninic acid sensitizes Notch3 activated ovarian cancer cells to carboplatin
Authors: Tzeng Tiffany J , Fu Yangxin , Cheng Wen‐Hsing
Published: June 2021

Ovarian cancer is the deadliest of gynecologic cancers and is usually diagnosed at advanced stage due to invalidated screening test. Although carboplatin has been used for treating ovarian cancer for years, ovarian cancer eventually develops resistance to this platinum‐containing drug. Animal studies have demonstrated efficacies of methylseleninic acid (MSeA) in counteracting tumorigenesis. Expression of Notch3 is associated with chemoresistance and correlated with poor overall survival of human ovarian cancer patients. Here we tested the hypothesis that MSeA can sensitize OVCA429/NICD3 cells to carboplatin treatment. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) rendered them resistance to carboplatin compared to OVCA429 cells transduced with an empty vector (OVCA429/pCEG). Co‐treatment with MSeA sensitized OVCA429/NICD3, but not OVCA429/pCEG cells to carboplatin treatment. These two chemicals appear to synergistically kill OVCA429/NICD3 cells, which can be suppressed by the presence of N‐acetyl cysteine or DNA damage kinase inhibitors of ATM and DNA‐PKcs. In summary, MSeA sensitizes OVCA429/NICD3 cells to carboplatin treatment in a pathway involves oxidative stress, ATM and DNA‐PKcs, suggesting a new strategy to improve the efficacy of carboplatin treatment against ovarian cancer.

Grant Funding Source: UMCP
Effects of dehydrated Opuntia ficus indica (Nopal) consumption on adiposity and gut physiology in Sprague Dawley rats fed a high fat diet
Authors: MORAN‐RAMOS SOFIA , TOVAR ARMANDO R. , TORRES NIMBE , RAYBOULD HELEN
Published: June 2021

We have previously shown that Opuntia ficus indica (Nopal), a plant rich in dietary fiber and polyphenols is able to ameliorate hepatic steatosis in obese Zucker rats. However, its effect in high fat diet‐induced obese models has not been evaluated. Six weeks old male Sprague‐Dawley rats (n = 42) were fed with a low fat diet (LF) or a high fat diet (HF) for 4 weeks, The groups were then divided; one half of each group was assigned to a LF + Nopal (LF‐N) or HF + Nopal (HF‐N) and fed for a further 6 weeks.

Results

Nopal consumption significantly decreased adiposity and adipocyte hypertrophy and decreased serum leptin. Nopal consumption significantly increased the weight of cecal contents and cecal tissue regardless of the diet. Finally Nopal consumption decreased reactive oxygen species in the cecum and colon of HF rats. This study shows that Nopal consumption prevents HF diet‐derived adiposity. The significant association between adiposity, adipocyte size and cecum weight may imply that fermentation of the dietary fibers present in Nopal could be partly responsible for the changes observed in the adipose tissue. Supported by NIH DDK 41004 grant (HR)
Kaempferol suppresses lung airway fibrosis through modulating TGF‐β‐PAR‐1 activation in human bronchial epithelial cells and ovalbumin‐challenged mice
Authors: Gong Ju‐Hyun , Kang Young‐Hee
Published: June 2021

Chronic airway remodeling is characterized by structural changes within the airway wall, including smooth muscle hypertrophy, sub‐mucosal fibrosis and epithelial shedding. Epithelial to mesenchymal transition (EMT) is a fundamental mechanism of organ fibrosis, which can be induced by TGF‐β1. Protease‐activated receptor (PAR) has been known to contribute to the pathogenesis of various pulmonary diseases. However, little is known about the localization of PAR‐1 in lung airway and relationship between PAR‐1 and EMT. In vitro study, we investigated whether kaempferol inhibited TGF‐β1‐induced bronchial epithelial EMT for 72 h. TGF‐β1 resulted in a striking loss of epithelial morphology by displaying fibroblast appearance. Kaempferol at ≤20 μM significantly inhibited TGF‐β1‐induced collagen secretion and α‐SMA induction through disturbing PAR1 activation dampened by SCH‐79797. In vivo study explored demoting effects of 10–20 mg/kg kaempferol on airway constriction responses in BALB/c mice sensitized with OVA. Kaempferol suppressed collagen deposition, smooth muscle cell excrescency and mucus secretion observed in the lung of OVA‐challenged mice. These results demonstrate that dietary kaempferol alleviated fibrotic airway remodeling via bronchial epithelial EMT by modulating PAR1 activation. Therefore, kaempferol may be a potential therapeutic agent targeting asthmatic airway constriction.
Effects of oriental plum extract on the cognitive function and the cerebral neurodegeneration‐related protein expressions in Type 2 diabetic rats
Authors: Liao Hsiang , Lee Kao‐ting , Chien Yi‐wen , Lin Shyh‐Hsiang
Published: June 2021

Recent studies indicate that Type 2 diabetes mellitus (T2DM) is one of the risk factors of Alzheimer's disease (AD). An impaired insulin signaling caused by insulin resistance may result in abnormal protein expressions in the brain and neuron damages. The study aimed to investigate the prevention of AD type neurodegeneration by consuming polyphenols‐rich oriental plum (Prunus salicina Lindl) extract on T2DM rats. Nicotinamide/streptozotocin‐injection was performed to induce T2DM on male Wistar rats, followed by a 2 months oriental plum extract (OP) feeding intervention. The results showed that OP intervention significantly reduced insulin resistance by improving the Homeostasis model assessment‐insulin resistance (HOMA‐IR). Morris water maze results indicated the spatial learning function was improved after the OP consumption. The intervention also reduced amyloid‐β (Aβ) and phosphorylated tau (p‐tau) protein levels in the cerebral cortex and reduced Aβ deposition in the hippocampus of the T2DM rats. In conclusion, the oriental plum extract decreased the cognitive decline and reduced the expressions of AD‐type pathological proteins Aβ and p‐tau in T2DM rats.

Grant Funding Source: Taipei Medical University
Grape intake exerts diverse tissue pharmacogenomic effects in model of metabolic syndrome
Authors: Seymour E Mitchell , Lewis Sarah , Bolling Steven F
Published: June 2021

The metabolic syndrome (MSn) predisposes one to Type II diabetes and cardiovascular disease, and inflammation and oxidative stress participate in MSn‐related organ pathophysiology. Intake of fruits/vegetables modifies risk of MSn, and phytochemicals and their pharmacodynamic effects may be vital to these observed health effects. Grapes are a rich, whole‐food source of phytochemicals. In the obesity‐prone Zucker Fatty rat, we tested the effect of an American‐style diet with added whole table grape powder (3% w:w). Rats were fed for 90 days. Compared to a macronutrient and calorie‐matched control group, grape intake significantly reduced serum C‐reactive protein, TNF‐α, and IL‐6. Grape also reduced liver, kidney, and abdominal fat weight amongst several other phenotypes. Pharmacodynamic effect was measured by changes in NF‐κB‐related and antioxidant‐related mRNA/proteins in the heart, abdominal fat, skeletal muscle, liver, brain, renal cortex, and renal medulla. NF‐κB‐related mRNA/proteins appear most significantly reduced in liver and abdominal fat. Antioxidant defense mRNA/proteins were most significantly increased in liver and renal cortex. Grape pharmacogenomic effects may be critical because these tissues/organs participate in MSn phenotypes like fatty liver, hypertension, and central adiposity. Supported by California Table Grape Commission, F31HL087720, and R21AT004588.
Defining walnuts’ inhibition of prostate cancer growth in TRAMP mice
Authors: Davis Paul Andrew , Kim Hyunsook , Yokoyama Wallace
Published: June 2021

Dietary changes potentially reduce prostate cancer morbidity and mortality. Based on (Davis et al BrJNutrition 2012), the tumor response to 100g of fat/kg diets (macronutrients, tocopherols(α and γ ) matched; N=75 TRAMP mice fed ad lib for 18wks) A‐whole walnuts, B‐a fat blend matching walnut fatty acid profile and C‐walnut oil from same walnuts. Fasted plasma glucose, prostate(GUI–genitourinary unit intact) obtained, weighed and frozen. Plasma TG, lipoprotein cholesterol, plasma multianalyte(Rat MetabolicMAP), prostate tissue metabolites (Metabolon) and mRNA (Illumina NGS) were analyzed. Prostate tumor size decreased in both A and C compared to B (p<0.05). Plasma IGF1 and LDL cholesterol decreased in A and Cvs.B (p<0.05) while most plasma results were unchanged. GUI showed 16 and 95 metabolite level changes in A and C respectively with 9 shared compared to B. mRNA changes in A (213) and C(41) vs B, with 17 shared (e.g. COX2 decreased) in A&C. Walnut oil associated, non fatty acid component(s) decreased plasma IGF‐1 and prostate COX‐2 mRNA levels and inhibited tumor growth.
Visfatin and vaspin protein concentrations in different tissues and insulin resistance
Authors: Goktas Zeynep , Wang Shu
Published: June 2021

Background

In obesity, adipose tissue secretes many adipokines that have functions in insulin sensitivity. Visfatin and vaspin are known as insulin‐mimetic proteins and they might stimulate glucose uptake. Our research focuses on tissue visfatin and vaspin concentrations and their relationships to insulin resistance.

Methods

Thirty eight morbid obese (BMI ≥40) subjects had the subcutaneous, omental, and mesenteric adipose tissue, liver and muscle tissue samples taken at the time of Roux‐n‐Y surgeries. Visfatin and vaspin proteins were measured using ELISA kits. Fasting blood glucose and HbA1c levels and HOMA‐IR were measured before the surgery. Results were analyzed using ANOVA and Pearson correlation.

Results

Liver had significantly higher visfatin and vaspin concentrations than other tissues. There wasn't any significant difference in visfatin and vaspin concentrations among three different adipose tissues. Omental adipose tissue visfatin concentrations were positively correlated with HOMA‐IR and blood HbA1c levels (r = 0.456 and r = 0.481, respectively). Mesenteric adipose tissue vaspin concentrations were positively correlated with HOMA‐IR, blood glucose and HbA1c levels (r = 0.578, r = 0.467, and r = 0.455, respectively).

Conclusions

Our findings indicate that tissue visfatin and vaspin protein concentrations are involved in the development of insulin resistance during obesity.

Grant Funding Source: TTU Research Fund
A pilot study of TLR4 polymorphism in relation to intestinal dysbiosis and risk of necrotizing enterocolitis in preterm infants
Authors: Taft Diana H , Kottyan Leah , Lagomarcino Anne J , Schibler Kurt R , Yu Zhuoteng , Gevers Dirk , Ward Doyle V , Huttenhower Curtis , Newburg David S , Morrow Ardythe L
Published: June 2021

Necrotizing enterocolitis (NEC) is a devastating disease of prematurity, hypothesized to be due in part to excessive inflammatory signaling of toll‐like receptor 4 (TLR4) in response to the lipopolysaccharide (LPS) of Gram‐negative organisms. In this pilot study, we tested the hypothesis that polymorphisms in TLR4 modify the risk of developing NEC associated with intestinal dominance by Gram‐negative organisms (Proteobacteria). Using the Illumina ImmunoChip we analyzed TLR4 polymorphisms of 24 infants <29 wks gestational age enrolled in a study of the intestinal microbiome. Six infants who developed NEC after Proteobacteria dysbiosis (>;90% of the intestinal microbiome comprised of Proteobacteria) were compared to 18 control infants with varied microbial communities. One TLR4 polymorphism, rs10759932, occurred significantly more often in NEC cases (4 GA, 2 AA) compared to all controls (2 GA, 16 AA; Fisher's exact test, p=0.018) or compared only to the 7 controls identified with a Proteobacteria dysbiosis (7 AA, p=0.021). These findings support the hypothesis that NEC may occur as the result of host immune response to the microbiome. A larger study of microbial colonization and host genetics is ongoing.

Project funded by NIH HD 05491, NIH T32 ES 010957–12, NIAID NIH HHS Contract No. HHSN272200900018C

Grant Funding Source: NIH HD 05491, NIH T32 ES 010957–12, and NIAID NIH HHS Contract No. HHSN272200900018C
Select Amino Acids Induced Expression of Human Beta‐Defensin in Caco‐2 cells
Authors: Osei‐Boadi Kate , Gordon Emma , Melgarejo Tonatiuh
Published: June 2021

Host defense peptides (HDPs) are important components of the innate immune system and contribute to protection of the intestinal epithelium. Human beta defensin 2 (HBD2) is a HDP expressed by the epithelial cells of skin, gastrointestinal tract and the respiratory tract and plays an important role in protecting these tissues. The objective of this study was to investigate the role of specific amino acids in inducing human defensin‐2 in Caco‐2 cells. Previous studies showed individual amino acids such as isoleucine, glutamine, or arginine inducing HDP in epithelial cells. There appears to be a gap in information on which extent a combination of different amino acids influence the expression of beta defensins. Here we look at the role of isoleucine, arginine and glutamine (all L‐forms, individually or in combination) in inducing the expression of HBD2 in Caco‐2 cells. Cell lines were grown and exposed to different concentrations of amino acids. The effect of time and concentration of the different amino acids (alone or combined) on the expression of HBD2 was determined. HBD2 expression was evaluated using RT‐PCR with specific forward and reverse primers for HBD2. Results from our preliminary studies show that HBD2 expression by Caco‐2 cells is enhanced by a combination of at least two amino acids at a μmol concentration. Amino acids as immunomodulators have promising clinical implications in gastrointestinal disorders. (Kansas State University, NHHNSROAES)
High renal calcium (Ca) excretion does not reduce femur bone density in mice fed adequate or low dietary Ca
Authors: Fernandez Perla Citlali Reyes , Fleet James C
Published: June 2021

Active vitamin D, 1,25(OH)2D3 (1,25D) regulates intestinal Ca absorption (Ca Abs) under low dietary Ca intake by inducing gene expression through the vitamin D receptor (VDR). Vitamin D‐regulated Ca Abs is greatest in the proximal small intestine but VDR is highest in the large intestine. We generated transgenic (TG) mice using a CDX2P9.5 promoter‐Cre transgene to drive deletion of floxed VDR alleles from the lower bowel to test whether this disrupts whole body Ca metabolism. Weanling, male TG and control mice were fed diets with low (0.25%) or normal (0.5%) Ca levels until 10 wks of age. Transgene expression was seen in the distal ileum, cecum, and colon as well as the kidney, a 1,25D target tissue. Serum 1,25D was not different between genotypes and serum Ca was normal in all groups. TG mice had low serum PTH (p<0.001) which explains the 10‐fold higher urinary Ca/creatinine ratio (p<0.001) we observed. However, no genotype effects were found in femur cancellous or cortical bone density. These data show that while Ca metabolism is disturbed in TG mice, high renal Ca excretion does not negatively affect bone density or adaption to restricted Ca intake.

Grant Funding Source: NIH award DK54111 (JCF)
Serum amyloid A and Toll‐like receptor 2 activation promote de‐differentiation of vascular smooth muscle cells
Authors: Pessolano Lawrence G , Seidl Stephanie E , Rich Celeste B , Schreiber Barbara M
Published: June 2021

Smooth muscle cells (SMCs) regulate vascular tone, and during chronic inflammation associated with atherosclerosis, SMCs contribute to the disease process via de‐differentiation from a contractile state. We study the impact of acute phase serum amyloid A (SAA), a cardiovascular risk marker that localizes to atherosclerotic plaques, on SMC function. The goal of this study was to define a role for SAA in SMC phenotypic expression. SMC marker expression was down‐regulated by SAA, consistent with de‐differentiation. Myocardin, a transcriptional co‐activator of SMC marker gene expression, was down‐regulated by SAA, and its overexpression rescued the SAA‐mediated repression of the smooth muscle α‐actin and smooth muscle 22 α (SM22) promoters. SAA‐mediated down‐regulation of SM22 promoter activity was also rescued by expression of the myocardin family members, myocardin related transcription factor (MRTF)‐A and MRTF‐B. It was reported that SAA is a ligand for the Toll‐like receptor (TLR)2, which has been implicated in atherosclerosis. Interestingly, FSL‐1 and Pam3CSK4, known TLR2 ligands, down‐regulated SM22 promoter activity, and the effects were rescued with myocardin overexpression. Moreover, knockdown of TLR2 using siRNA rescued the de‐differentiated phenotype induced by SAA. These data suggest that SAA and TLR2 activation promote SMC de‐differentiation characteristic of atherosclerosis.

This work was supported by NIH grant HL079201.
Cerebrovascular Endothelial Cell Activation in Paediatric Diabetic Ketoacidosis
Authors: Omatsu Tatsushi , Cepinskas Gediminas , Fraser Douglas D
Published: June 2021

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications. The mechanisms of DKA‐induced vascular dysfunction are unclear. We aimed to assess the effects/mechanisms of DKA plasma on activation of human cerebrovascular endothelial cells (hCMEC/D3; provided by Dr. P.O. Couraud, INSERM).

Methods

DKA‐blood plasma was obtained from paediatric patients with either DKA or well‐controlled type‐1 diabetes (control; CON). The levels of 21 inflammation‐relevant analytes in blood were assessed. In vitro hCMEC/D3 were stimulated with 20% (v/v) CON‐ or DKA‐plasma and assessed for activation markers.

Results

DKA in children resulted in increased circulating levels of IL‐2, IL‐6, IL‐8, GRO, INFα2, and G‐CSF. Stimulation of hCMEC/D3 with DKA‐plasma induced production of ROS and increased PMN‐leukocyte adhesion to hCMEC/D3 under “flow” conditions (shear stress 0.35 dyn/cm2). PMN adhesion was replicated by stimulating hCMEC/D3 with IL‐8 and/or GROα (at the levels detected in DKA‐plasma), the phenomenon that was suppressed by neutralizing anti‐CXCR1 and/or CXCR2 antibodies.

Conclusions

DKA elicits systemic inflammation associated with increased oxidative stress and up‐regulation of the pro‐adhesive phenotype in cerebrovascular endothelium, potentially contributing to DKA‐associated intracranial vascular complications.
Acceleration of liver regeneration by betaine supplementation via enhancement of sulfur‐containing amino acid metabolism
Authors: Ahn Chul Won , Jun Doo Sung , Kim Young Chul
Published: June 2021

Our earlier work showed that hepatic S‐adenosylmethionine (SAM) level was critically associated with liver regenerative process. In this study we examined the progression of liver regeneration in the rats treated with betaine, a methyl donor that increases the generation of SAM in liver. Male rats received betaine in drinking water from 2 wk prior to 2/3 partial hepatectomy (PHx). Liver growth was more rapid in the rats treated with betaine from 48 h after PHx. Induction of cyclin D1 expression in liver was accelerated, and remained elevated for 24 h. Proliferating cell nuclear antigen expression in liver was significantly greater in the betaine‐treated rats at 24 and 48 h after the surgery. Methionine, SAM, cysteine, glutathione, and taurine were all increased by PHx. The increase in methionine and SAM was intensified significantly in the rats provided with betaine. The surgical treatment elevated putrescine and spermidine, but decreased spermine levels in the remnant livers. Betaine treatment markedly enhanced the elevation of putrescine and spermidine levels. In conclusion, the results suggest that betaine may be useful as a therapeutic liver‐regenerating agent both in the remnant liver and in the transplanted liver. The elevation of hepatic SAM, a metabolic substrate for polyamine synthesis, appears to play an important role in the acceleration of liver regeneration in the rats treated with betaine.
PET‐CT analysis of cererbral glucose metabolism in patients with post‐operative cognitive dysfunction
Authors: Herter Jan Michael , Brenscheid Niko , Nienhaus Lydia , Dieterich Charlotte , Van Aken Hugo , Weckesser Matthias , Stubbe Henning Dirk
Published: June 2021

Post‐operative cognitive dysfunction (POCD) is a perioperative complication with a reported incidence of approx. 25% among the elderly in non‐cardiac surgery. Several studies have revealed that patients with POCD have a poorer prognosis compared to control groups. However, the pathophysiology of POCD remains elusive. Recent reports have postulated a common disease mechanism for POCD and Alzheimer's disease. We conducted a clinical study to assess POCD incidence among elderly patients (>;70 yrs.) undergoing major non‐cardiac surgery (>;2h) under general or combined anesthesia and stratify for risk factors. Initially, 87 patients were included and tested preoperatively. However, 23 patients refused postoperative retesting or revealed preexisting dementia and were thus excluded. In the POCD positive study population (n=20, 31%), 10 patients underwent PET‐CT analysis as part of the clinical workup to assess postoperative cognitive decline. We here report that 7 of these patients revealed significant cerebral glucose metabolism impairment, 3 of which resembled a pattern typically seen in neurodegenerative disease. POCD may thus result from alterations in brain metabolism.
Three Rodent Strain‐wide comparisons: Cardio‐pathological markers in a mouse model subjected to repeated social aggressor
Authors: Melige Monique Marie N
Published: June 2021

Post‐traumatic stress disorder (PTSD), a common psychiatric disorder, is associated with the risk of cardiovascular (CV) atrophy and possible thromboembolic stroke. We examined the histology of cardiac samples from three mouse strains (C57BL/6j, BALB/cj and DBA/2j) that had been subjected to aggressor exposure (Agg‐E) for 5 or 10 d. Agg‐E mice were socially stressed; housed with aggressor mice (Agg) for 6 h/d without access to food/liquid and subjected to direct exposures with Agg at 3x/d at random times. Control mice (C) were put in the same environment without Agg. Cardiac tissues were harvested 1 d or 4 wks after 10‐day Agg‐E, and 1 d or 1.5 wks after 5‐day Agg‐E schedule, and were stained and examined using bright field microscopy. Cardiac tissues from C were harvested at the same time points.

Agg‐E induced cardiomyopathy, specifically degeneration and inflammation, was mostly evident 1 d after 10‐day and 5‐day schedule among the Agg‐E mice of C57BL/6j. BALB/cj displayed a modest effect of stress; whereas DBA/2j displayed no sign of ailment.

Mice of all three strains showed almost no trace of CV atrophy 4wks after 10‐day Agg‐E schedule; although after 1.5 wks post 5‐day schedules, traces of CV atrophy persisted only in C57BL/6j.

In conclusion, C57BL/6j showed most effect of acute stress recovered with rest period. BALB/cj displayed a modest effect of stress and DBA/2j emerged as the most resilient strain.
USE OF THE PROXIMITY LIGATION ASSAY TO DETECT IMMUNE COMPLEXES IN HISTOLOGIC SECTIONS
Authors: Petrosky Keiko , Merriam Kim , Rottman James B
Published: June 2021

The Proximity Ligation Assay (PLA) combines elements of immunohistology and molecular biology to allow for in‐situ detection of specific proteins, protein modifications, and protein‐protein interactions. PLA is often used to study the interaction of signaling cascade phosphoproteins on cytospin preparations of cultured cells. We demonstrate that the PLA can be adapted to detect immune complexes in archived tissue sections. We established immune complexes in sections of H929 xenografts, which constitutively express human antibody kappa light chains, by incubating the sections with either mouse‐anti‐human light chain monoclonal or anti‐human IgG polyclonal antibodies. We then used multicolor immunofluorescence to confirm that both mouse and human antibodies specifically co‐localized to the H929 cells in the xenograft. Although multi‐color immunofluorescence indicates whether two proteins are located in the same general vicinity, it does not prove that the two proteins are bound to one another. In contrast, the PLA generates a fluorescent signal via rolling circle DNA amplification only when two proteins are bound to one another. Using the PLA, we confirmed that the mouse antibodies formed immune complexes with the constitutively expressed human antibodies in the cytoplasm of the H929 xenograft cells. PLA may be useful to detect the presence of immune complexes in both preclinical and clinical samples.
Immunohistochemical localization of arginase‐1 expression in B6 and BALB/c mice
Authors: Meyerholz David K
Published: June 2021

Arginase is the final enzyme of the urea cycle hydrolyzing L‐arginine to ornithine and urea. The isoform arginase‐1 has been suggested to play a role in cardiovascular disease, cystic fibrosis, asthma and cancer. The goal of this study was to develop and validate immunohistochemical detection of arginase‐1 in formalin‐fixed paraffin embedded mouse tissues from B6 and BALB/c strains. Immunohistochemistry was performed using a primary Ab (polyclonal rabbit anti‐arginase‐1) with optimization/validation using the liver, where zone 1–2 hepatocytes express arginase‐1, but zone 3 lacks cellular expression. Tissues with prominent arginase‐1 cellular expression included liver, endocrine pancreas, lymphoid tissues, esophagus, skin, lung, thyroid, parathyroid, bone marrow, intestine, spleen, salivary glands and clitoral glands. Various disease states were also examined. Normal lymphoid cells in spleen had moderate diffuse arginase‐1 expression, but neoplastic lymphocytes lacked arginase‐1 expression. Hepatocytes, in a liver infiltrated by lymphoma, had enhanced arginase‐1 expression. Lungs with eosinophilic crystalline pneumonia commonly had alveolar macrophages with strong immunostaining. Endothelial cells of vessels had common immunostaining, while erythrocytes and platelets were negative. Smooth muscle of various tissues had multifocal uncommon immunostaining. There was no evidence of strain‐dependent differences in arginase‐1 expression. The diversity of tissues and cells that expressed arginase‐1 emphasizes the potential importance of arginase‐1 in disease models.
Mechanism of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)‐Induced Dilation of Middle Meningeal Artery: Role of ATP‐Sensitive Potassium (KATP) Channels
Authors: Syed Arsalan U. , Koide Masayo , May Victor , Wellman George C.
Published: June 2021

Migraine is a complex neurological condition that presents as intense episodic unilateral headaches accompanied by nausea, photophobia, phonophobia and other neurological symptoms. The causes of migraine headache appear multifactorial but may involve dilation of the meningeal vasculature. Intravenous injection of the neuropeptide PACAP induces migraine‐like symptoms and dilation of the middle meningeal artery (MMA) in both healthy and migraine patients. We have recently shown that PACAP dilates isolated pressurized MMA from the rat with a 1000‐fold higher potency compared to other vascular beds via activation of the high affinity Gs/cAMP‐coupled PAC1 receptor. It has also been shown that the cAMP/PKA pathway can activate KATP channels in vascular smooth muscle leading to vasodilation. In the present study our goal was to decipher if picomolar concentrations of PACAP activate KATP channels to induce MMA dilation. The KATP channel opener cromakalim induced a concentration‐dependent dilation of MMA with an EC50 of 100 nM, providing evidence of functional KATP channels. Further, PACAP‐induced MMA dilation was abolished by the KATP channel blocker glibenclamide. These observations indicate that PACAP dilates MMA via activation of vascular KATP channels which may play role in the etiology of migraine. Supported by NIH P01 HL095488, Totman Medical Research Trust and the Peter Martin Fund.
A novel ruthenium nitrosyl complex ameliorates L‐NAMEinduced bladder dysfunction
Authors: Santos Claudia F , Campos Rafael M , Nascimento Nilberto RF , Fonteles Manasses C
Published: June 2021

The present work was undertaken in order to screen the ruthenium NO‐donor complex, Rut‐BPY, in urodynamic parameters of 28‐ day L‐NAME‐treated rats. Three groups were studied: 1) L‐NAME control‐ Male wistar rats treated with L‐NAME in the drinking water (~60mg/Kg) during 28 days; 2) Ru‐BPY treated – Rats received L‐NAME in the drinking water as the former group but in the 14th day a mini‐osmotic pump delivering Rut‐BPY (10ηM/Kg/h) was implanted in the neck and kept for the remaining 14 days; and 3) Control rats that did not receive L‐NAME and were sham operated. At the end of the treatment period, animals were anesthetized and a catheter coupled to a pressure transducer was implanted in the bladder dome. Saline was infused into the bladder at the rate of 100 μl/min and both filling and voiding phases were studied. This study was approved by the Committee for Ethics in Animal Experimentation (CEUA document n∘ 08628332–4). L‐NAME induced a 54,90% increase in the number of non‐voiding contractions and in the group treated with Rut‐ BPY these values were similar to the control. The voiding threshold pressure was increased in the Rut‐BPY‐treated group by 63 % when compared to the L‐NAME group. The voiding frequency was increased by 56% and the residual bladder volume was decreased by 52% by Ru‐BPY (p<0,05). Rut – BPY ameliorate some of the lower urinary tract symptoms of the L‐NAME vesical dysfunction model.

Financial Support: CAPES, FUNCAP. CNPq.
Life as a minority scientist in industry and academia
Authors: Dotson Garry D
Published: June 2021

Presently, the challenges facing research scientist in both industrial and academic settings are many. Among these challenges are, training/maintaining a highly skilled workforce, integrating diverse scientific disciplines in solving complex societal problems, and maintaining a robust research program in a tough economic climate. Under‐represented minority scientists facing such challenges also have to overcome institutional barriers which may lead to issues of isolation, under‐valuation, and disparities in funding and promotion/progression opportunities in order to attain professional success. Experiences of under‐represented scientist who have had careers which span both industry and academia can provide the research community with a unique vantage point from which to survey progress and to plot effectively a more inclusive future course.
Participation of cyclooxygenase and PGs E2 and F2alfa during the development of the rat in the contractile effect of phenylephrine in rat aorta and coronary artery
Authors: Acevedo‐Villavicencio Nallely , Lopez‐Calderon Emilio , Ramirez‐Sachez Israel , Guevara‐Balcazar Gustavo , Castillo‐Hernandez Maria Carmen
Published: June 2021

The aim of this paper is to analyze the changes of cyclooxygenase (COX) and prostaglandins (PGs) E2 and F2alfa involvement in the contractile response to phenylephrine in the thoracic and abdominal aorta and coronary artery of prepubertal young and old rats. It has been describe that during development there are changes in the activity of some enzymatic pathways, in this work we analyze the change in the involvement of cyclooxygenase and PGs in the contractile effect of phenylephrine with age. COX 1 and 2 have been related in the release of prostanoids that regulate the effect of various agonists as in the case of phenylephrine, but its unknown that how this enzyme is involved during the development of the rat cardiovascular level. In this experimental model we used male rats of 6, 16 weeks and 1 year of age. Rats were anesthetized with pentobarbital (50 mg/kg), after that we proceeded to obtain the thoracic aorta and abdominal aorta and the heart. The aortic rings were placed in an isolated organ system which keeps the tissue in physiological Krebs solution at a temperature of 37 ° C and bubbled with carbogen (95% O2 and 5% CO2) and the other hand the heart were placed in a Langendorf system. Then we proceeded to make concentration response curves to phenylephrine (10–9 to 10–5M) in the presence and absence of indomethacin, NS 398 and Sc560 (COX antagonist). We obtain 20mg of either heart, thoracic or abdominal aorta for the western blot analysis of COX 1 and COX 2 and for the PGS measurement. Results showed differences in participation of this enzyme and PGs in the contractile response to phenylephrine age‐dependent rat.
The Dopamine Receptor‐Interacting Protein S100B: Consequences and Site of Binding
Authors: Neve Kim Arthur , Lee Hun‐Joo , Buck David , Liu Yong
Published: June 2021

S100B is a calcium‐binding protein that mediates numerous activities in the mammalian brain. With a bacterial two‐hybrid assay we identified a novel interaction between S100B and the third cytoplasmic loop of the dopamine D2 receptor (D2‐IC3). The binding of S100B to D2‐IC3 was confirmed using polyHis pull‐down and FLAG co‐IP assays, and was highly sensitive to the presence of Ca2+. The binding of heterologous S100B to full‐length D2 receptor in HEK293 cells, and of endogenous S100B to endogenous D2 receptor in the rat neostriatum, was demonstrated by co‐IP. Despite the presence of a putative S100B binding motif near the N‐terminus of D2‐IC3, additional FLAG co‐IP assays identified binding determinants outside of that motif. S100B is thought of as a glial protein, but immunoreactivity for S100B was detected in microtubule‐associated protein‐2 (MAP2) expressing cells in neostriatal neuronal cultures. Expression of S100B in HEK293 cells also stably expressing the D2 receptor significantly increased D2 receptor stimulation of extracellular signal‐regulated kinases (ERKs), while causing little change in NGF‐stimulated activation of ERKs, and enhanced D2 receptor inhibition of adenylate cyclase. Taken together, these findings suggest that the interaction of S100B with the D2 dopamine receptor enhances D2 receptor function. (MH045372 and VA Merit Review)
Pharmacological Potentiators of TRPM5 Channel Activity
Authors: Siehler Sandra , Reinhardt Juergen , Kaufmann Markus , Dzhura Igor , Erdemli Gul
Published: June 2021

TRPM5 belongs to the ‘melastatin’ transient receptor potential subfamily, fluxes mainly Na+, and is activated by cytosolic Ca2+ increases (< 1 μM). TRPM5 activates and deactivates rapidly even during sustained Ca2+ rises, which leads to transient membrane depolarization kinetics. Only the Ca2+ ionophore ionomycin yielded significant and transient membrane potential (MP) signals in HEK293 cells stably expressing TRPM5. Various agonists for endogenous Gq‐GPCRs induced significant Ca2+ signals, but did not or only weakly activate TRPM5. Five tool potentiators were assessed using two TRPM5‐expressing cell clones, and various pharmacological concentrations of the indirect stimulator ionomycin. For both cell lines, potencies and efficacies of potentiators were best using an EC80 (rather than an EC20) concentration of ionomycin. This indirectly indicates that maximal cytosolic Ca2+ increases lead only to submaximal TRPM5 activation. EC60–80 concentrations of ionomycin yielded acceptable MP assay statistics, and a focused compound library was tested to find further and more potent TRPM5 potentiators. 114 TRPM5 potentiator hits were found (EC50 values: 0.11 –40 μM), and 67 thereof confirmed in a patch clamp assay. 38 of these novel TRPM5 potentiators increased currents over 100%. This work was supported by the Novartis Institutes for BioMedical Research (NIBR).