bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saturated dietary fat prevented unsaturated fat and alcohol‐mediated alterations in gut microbiota resulting in attenuation of intestinal barrier disruption and liver injury in an animal model of alcoholic liver disease (822.9)
Authors: Kirpich Irina , Feng Wenke , Wang Yuhua , Liu Yanlong , Barve Shirish , McClain Craig 
Published: June 2021

Introduction: Gut microbiota play an important role in the pathogenesis of ALD. Dietary fat and alcohol both affect microbiota composition and abundance. The aim of the study was to evaluate the effects of different types of dietary fat on alcohol‐mediated changes in gut microbiota and consequent intestinal and liver injury. Materials and Methods: C57BL/6 mice were fed either saturated (medium chain triglycerides enriched [MCT]) or unsaturated (corn oil enriched) fat diet containing 5% ethanol for 8 weeks. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3‐V5 regions of the 16S rRNA gene and large‐scale parallel pyrosequencing on the 454 FLX Titanium platform. Intestinal barrier integrity; liver injury and steatosis were evaluated. Results: Dietary unsaturated fat and ethanol caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla. The observed microbiota changes were associated with the alterations in the intestinal tight junctions; liver inflammation and injury. Notably, unsaturated fat and ethanol induced pathogenic alterations in the gut microbiome, intestinal barrier integrity, and the livers were prevented in animals receiving saturated fat diet and ethanol. Conclusion: ALD relevant pathogenic alterations in the gut microbiome induced by chronic ethanol are markedly influenced by dietary lipids. Dietary lipids can potentially provide therapeutic options in the management of ALD.Grant Funding Source: Supported by NIH, DOD and Veterans Administration
Nutritional evaluation of HIV positive and exposed children from the Takalik Abaj region of Guatemala (828.7)
Authors: Alfonso Victor , de Ponce Silvia , Villanueva Lisa , Reinhart Gregory 
Published: June 2021

As part of a feeding study undertaken in Retalhuleu, 6 HIV positive and 41 HIV exposed children 6‐72 mo of age attending a Nutritional Attention Unit in Coatepeque were nutritionally evaluated. Anthropometric and biomarker data were collected to calculate the prevalence of acute and chronic malnutrition, muscle mass depletion, chronic inflammation, anemia, and deficiency of iron, zinc, folic acid, vitamin B12 and iodine. Feeding patterns for children under 36 mo was also established. The results revealed that 23.5% of the children presented with acute malnutrition (WAZ < ‐1) and 78.2% had chronic malnutrition (HAZ < ‐1). Muscle mass depletion, using WHO standards for MUAC, was found in 33.2% and anemia in 20.3% of the children. Nutritional deficiencies were noted for serum folic (45%), erythrocyte folic acid (5.4%), vitamin B12 (8.7%), zinc (50%), iodine (41.3%) and iron (34.1%). The prevalence of chronic inflammation (AGP > 1g/L) was 11.3%. The feeding pattern of these children consisted of: corn tortilla, noodles, rice, oranges, bananas, sausage, chicken, eggs, black beans, sugar, water, coffee and natural beverages. In conclusion, HIV positive and exposed children in this region of southwestern Guatemala are at high risk of developing malnutrition. Nutritional compromise may burden an already challenged immunes system, decrease quality of life and decrease the likelihood of a favorable prognosis.Grant Funding Source: The Mathile Institute for the Advancement of Human Nutrition®
Effects of a soy protein diet on serum leptin and isoflavones in obese versus lean Zucker rats (829.5)
Authors: Hakkak Reza , Korourian Soheila , Sepehr Estatira , Doerge Daniel 
Published: June 2021

The obesity epidemic in the US continue to rise. Obese women have higher mortality rates from all cancers including breast cancer. Studies suggest health benefits from soy consumption in reducing cardiovascular disease and certain types of cancer but the mechanisms are poorly understood. The objective of this study was to determine the effects of a soy diet on serum leptin and isoflavone levels in obese animals. Lean and obese female Zucker rats (n=34) were randomly assigned to diets containing: 1) caseinate, or 2) soy protein isolate for 8 weeks. Serum leptin was measured by ELISA and total isoflavones (measured as aglycones genistein, daidzein and equol) were measured by liquid chromatography−tandem mass spectrometry (LC‐MS/MS). Serum leptin levels were increased in obese vs lean animals on both diets (P<0.001)). Isoflavones were not detected in serum from the casein diet group. Serum total genistein (0.88 + 0.28 vs 1.18 + 0.5 µM) and daidzein (0.43 + 0.70 vs 0.59 + 0.24 µM) (lean vs obese rats, respectively) were not affected by obesity in the soy diet group but obesity caused a significant (P<0.05) reduction (1.40 + 0.46 vs 0.98 + 0.25 µM) in serum total equol levels. Our results suggest that isoflavone metabolism in the obese female Zucker rat model is altered compared to lean animals resulting in decreased equol formation by GI microflora following dietary soy consumption.Grant Funding Source: The UAMS Children’s University Medical Group
Polyphenol blend reduces oxidative stress induced by heat stress in piglets (830.19)
Authors: van Kempen Theo , Fevery Sofie , Michiels Joris , De Smet Stefaan , van Hees Hubert 
Published: June 2021

Polyphenols selected for bio‐availability can function as anti‐oxidants in animal tissues. As such, they may be better suited for managing oxidative stress than Vit. E whose impact easily saturates. To test this, newly‐weaned piglets were first put on diets devoid of Vit. E for 18 days. Subsequently, they were fed diets containing either 11 IU Vit. E (control), 80 IU Vit. E (80E), or 11 IU Vit. E + 69 IU Vit. E equivalent provided by a polyphenol blend (PB) containing rosmarinic and carnosic acid, curcumin, resveratrol, and naringenin. Seven days later piglets were submitted to heat stress known to induce oxidative stress: 40°C for 24h, flanked by blood sampling. Prior to heat stress, plasma superoxide dismutase (SOD) was lower for PB (3.43 U/ml, n=15) than controls (5.01, n=14), while 80E was intermediate (3.75, n=12). The ORAC value was highest in PB (10237 uM TE) and lowest for 80E (9217). Following heat stress, malondialdehyde (MDA) was lowest in PB (7.33 nM), intermediate in 80E (7.74), and highest in controls (8.41). There was also a trend for SOD to be highest in the controls. SOD and MDA were positively correlated (R2=0.76), as were FRAP and MDA (R2=0.41). In conclusion, the polyphenol blend offered at least as good a protection against oxidative stress in heat‐stressed piglets than a high dose of Vit. E.Grant Funding Source: Nutreco
Chronic consumption of a high polyphenol cranberry beverage protects against inflammation and improves endothelial function in healthy but overweight humans (830.26)
Authors: Kimble Lindsey , Mathison Bridget , McKay Diane , Chen C‐Y. Oliver , Blumberg Jeffrey , Kaspar Kerrie , Khoo Christina , Chew Boon 
Published: June 2021

Clinical trials with cranberry products have mainly focused on urinary tract health. We studied the effects of chronic cranberry beverage consumption on oxidative damage, inflammation, and endothelial function in overweight but otherwise healthy humans. Seventy eight men and women (30‐70 y) with abdominal adiposity (BMI: 27‐35 kg/m2; waist:hip >0.8 for women and >0.9 for men; waist:height 蠅0.5) consumed 15.2 oz placebo or a high polyphenol content cranberry extract beverage (CEB) daily for 8 wk in a randomized, double‐blind placebo‐controlled trial. Blood was collected at 0, 3, 5, and 8 h after challenge with an oral dose of glucose following a single dose of cranberry beverage (acute) and daily consumption for 8 wk (chronic). Compared to placebo, a single dose of CEB elevated (P<0.05) reduced glutathione and reduced:oxidized glutathione ratio in blood, indicating enhanced redox capacity. Consumption of CEB also decreased (P<0.05) endothelin‐1 and tended to increase (P=0.07) nitric oxide in plasma. Plasma IFN‐γ was elevated (P<0.05) after a single dose of CEB. After the chronic intervention, CEB decreased (P<0.05) IFN‐γ and C‐reactive protein, and tended to increase (P=0.07) superoxide dismutase activity. An acute dose of cranberry beverage improved redox status and endothelial function, while chronic consumption down‐regulated inflammatory biomarkers.Grant Funding Source: Supported by Ocean Spray Cranberries, Inc. and USDA
In vivo and in vitro studies on the antioxidant activity of hesperetin and its glycosylated derivatives (830.8)
Authors: Carvalho Patricia , de Franco Elida Paula , de Souza Verônica , de Araújo Maria Elisa , Franco Yollanda , Messias Márcia , Priviero Fernanda 
Published: June 2021

The effect of of hesperetin (HT), hesperidin (HG) and G‐hesperidin (GHD) on oxidative‐antioxidative system and lipid profile in rats was evaluated and correlated to their in vitro antioxidant activity. Twenty‐four macho wistar (n=6) fed with standard rat chow diet were supplemented with each flavonoid (1mmol/Kg) and saline solution (control group). TBARS, GPx, SOD and CAT levels were measured in hepatic tissue. The levels of triglyceride, total cholesterol and lipoprotein fraction cholesterol levels were measured in plasma. In vitro antioxidant was evaluated by DPPH radical‐scavenging and the kinetic parameters of xanthine oxidase inhibition were determined by Lineweaver‐Burk plots. GPx and SOD levels were significantly higher in HT and HD groups than those in control group. Both groups treated showed atherogenic index levels significantly lower compared to the control group. Hesperetin showed a greater in vitro antioxidant activity and was stronger xanthine oxidase inhibitor with IC50 value of 53µM and Ki value of 17.3µm. Although the aglycone form hesperetin showed higher scavenging activity against DPPH and the stronger xanthine oxidase inhibitor, the three compounds showed a positive change occurred in oxidative‐antioxidative balance in rats.Grant Funding Source: FAPESP 2012/20393‐4
Pecan supplementation modulates plasma paraoxonase activity in apolipoprotein E knockout mice fed high‐fat and high‐cholesterol diets (831.9)
Authors: Bolling Bradley , McAvoy Beth , Kim Bohkyung , Park Young‐Ki , Martin Derek , Xie Liyang , Lee Ji‐Young 
Published: June 2021

Pecans are a rich source of polyphenols and contain favorable lipid profiles which may improve cardiovascular disease risk. Apolipoprotein E knockout mice were fed high‐fat and high cholesterol diets or the same diet supplemented with 3.5% pecan or 7% pecan. At 4 wk, total cholesterol and triglycerides were not significantly different between supplemented and non‐supplemented groups. Mice supplemented with 7% pecans had 1‐fold greater liver isoprostanes than the 3.5% pecan and control groups determined by ELISA (P = 0.0156 by one‐way ANOVA). Both plasma and liver superoxide dismutase activities were not significantly different between groups. Plasma paraoxonase organophosphatase activity was increased by 42% and 97% from the control group in 3.5% and 7% pecan supplemented mice, respectively (P = 0.0101). In contrast, plasma and liver phenylacetate arylesterase and dihydrocoumarin lactonase activities, measures of paraoxonase‐1 and paraoxonase‐2 activities respectively, were not significantly different between groups. Thus, pecan supplementation increases paraoxonase organophosphotase activity, but not arylesterase or lactonase activities in Apolipoprotein E knockout mice.Grant Funding Source: Supported by the University of Connecticut College of Agriculture and Natural Resources
Metabolites of arachidonic acid acting in the small intestine mediate systemic and vascular inflammation in LDLR null mice (832.13)
Authors: Navab Kaveh 
Published: June 2021

We previously reported that a Western Diet increased levels of free arachidonic acid (AA) and its metabolites in the small intestine and plasma of LDLR null mice and increased plasma levels of serum amyloid A (SAA). To determine the role of AA metabolites in initiating inflammation, LDLR null mice on a chow diet were or were not administered 15‐hydroxyeicosatetraenoic acid (15‐HETE) at a dose of 5 μg/day (mixed into the chow) or the mice received 5 μg/day subcutaneously (SQ). After two weeks the mice were bled, perfused with saline to remove any remaining blood and the heart was harvested. Plasma levels of SAA were determined by ELISA and levels of free AA and its metabolites were determined in plasma by LC‐ESI‐MS/MS. Plasma SAA levels increased from 6.4 ± 1.9 ug/mL on chow without 15‐HETE to 15 ± 7 ug/mL with oral 15‐HETE (p<0.0001) and 15 ± 8 µg/mL with SQ (p = 0.0004). Plasma levels of free AA increased from 2435 ± 420 ng/mL on chow to 3274 ± 517 ng/mL with oral 15‐HETE (p<0.0001) and 2712 ± 479 ng/mL with SQ (p = 0.001). Three hours after the last SQ dose, plasma 15‐HETE levels were 0.9 ± 0.4 ng/mL on chow, 2.7 ± 1.5 ng/mL after oral (p<0.0001) and 1.5 ± 0.3 ng/mL after SQ 15‐HETE (p<0.0001). 5‐HETE and 12‐HETE levels also increased (p<0.001) and the magnitude of the changes were similar whether the 15‐HETE was administered orally or SQ. We conclude i) 15‐HETE administration increases plasma SAA, and free AA levels to a similar degree whether administered orally or SQ; ii) These results suggest that AA metabolites such as 15‐HETE can act in the small intestine to regulate systemic inflammation.Grant Funding Source: NIH
Optical versus impedance lamellar body counts on the Sysmex XT‐2000 automated hematology analyzer (834.13)
Authors: Desai Diana , Bennett Sterling 
Published: June 2021

Introduction: Respiratory distress syndrome, the ninth leading cause of newborn mortality in the US, is caused by fetal lung immaturity due to pulmonary surfactant deficiency. Lamellar body counts (LBC) are often employed for fetal lung maturity assessment. The Sysmex XT‐2000 hematology analyzer measures LBC in amniotic fluid using either impedance or optical platelet counts. The objective of this study was to compare impedance versus optical LBCs.Methods: LBC tests were performed on 18 residual frozen amniotic fluid specimens on a Sysmex XT‐2000 analyzer in an Intermountain Healthcare laboratory, following manufacturer’s instructions for impedance and optical platelet counts.Results: Results were highly correlated (r2=0.99). Mean impedance and optical LBC values were 60.6 and 62.1 x103/uL, respectively (p=0.0079). The mean difference between paired values was ‐2.7% (range ‐7.8% to +3.1%).Conclusions: Impedance and optical LBCs are highly comparable using the Sysmex XT‐2000 analyzer.
B cells from lupus‐prone mice respond more vigorously to lipopolysaccharide stimulation (835.5)
Authors: Roberts Rebecca , Kane Andrew , Doyle Chris , Orlick Andrew , Thiele John , Thiele Karla , Zuber Mathew 
Published: June 2021

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by its predominance in women and the production of autoantibodies by B cells. The causes of SLE are mostly unknown, but it has been linked to genetics, viruses and environmental factors. In order to determine how the immune system responds differently in an SLE context, this study investigated the response to lipopolysaccharide (LPS) by splenic B cells from two types of mice, control C57BL/6 and lupus‐prone NZB/WF1. Using fluorescence activated cell scanning (FACS) we found that NZB/WF1 mice have lower overall levels of splenic B cells than C57BL/6, making up 46% and 57.5%, respectively, of the total splenic lymphocyte cell population. However, those B cells are more responsive to LPS stimulation as indicated by a larger increase in blasting. Moreover, B cells from NZB/WF1 constitutively express lower surface levels of Major Histocompatibility Complex Class II (MHC‐II), yet again the relative increase upon LPS exposure is higher for NZB/WF1 (65%) compared to C57BL/6 (27%). A similar effect is seen for CD86, but not CD80. These findings may point to the importance of changse in B cell population in Lupus, where B cell overactivity is implicated in etiology.Grant Funding Source: Supported by Van Sant and a Center for Science and the Common Good mini‐grant sponsored by HHMI
Deletion of soluble epoxide hydrolase modulates coronary reactive hyperemia in isolated mouse hearts (837.10)
Authors: Hanif Ahmad , Zeldin Darryl , Nayeem Mohammed 
Published: June 2021

Coronary reactive hyperemia (RH) is impaired in hypertrophic hearts and in hearts with metabolic syndrome. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects against ischemia / reperfusion injury. Soluble epoxide hydrolase (sEH) is the main enzyme responsible for EETs breakdown. We hypothesized that in the absence of sEH, isolated mouse hearts exhibit increased RH through increased generation of EETs in response to no‐flow ischemia compared to wild type (sEH+/+). Coronary flow (CF) in isolated sEH+/+ and sEH‐/‐ mouse hearts was measured using Langendorff system. Perfused isolated hearts were exposed to 15 second ischemia and RH parameters were assessed. Following ischemia, flow repayment (calculated as the area under the curve and normalized to heart weight (ml/g)) was significantly higher in sEH‐/‐ compared to sEH+/+ hearts (7.62 ± 0.47 in sEH‐/‐ vs. 5.86 ± 0.68 in sEH+/+, p<0.05). Moreover, sEH‐/‐ hearts exhibited significantly higher repayment to debt ratio when compared to sEH+/+ hearts (2.06 ± 0.17 in sEH‐/‐ vs. 1.48 ± 0.14 in sEH+/+, p<0.05). No significant differences were observed in baseline coronary flow, debt area, peak hyperemic flow and repayment duration between the two groups. Our results demonstrate that RH, as measured by flow repayment and repayment to debt ratio, is significantly higher in sEH‐/‐ compared to sEH+/+mice. These data suggest that targeting or silencing sEH could have a beneficial effect on myocardial recovery from ischemia. Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ.Grant Funding Source: Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ
Acute increases of O‐GlcNAcylation reduces sepsis‐associated mortality (837.8)
Authors: Olivon Vania , Ferreira Raphael , Mestriner Fabíola , Alves‐Filho José , Cunha Fernando , Tostes Rita 
Published: June 2021

The post‐translational modification of proteins by O‐GlcNAcylation (O‐GlcNAc) is highly dynamic and modulates cell‐signaling processes. Acute increases in O‐GlcNAc levels reduce migration of inflammatory cells and the release of pro‐inflammatory mediators, important events in sepsis caused by bacterial infection or multiple non‐infectious causes. This study tested the hypothesis that acute increases of O‐GlcNAc levels reduce mortality and inflammatory processes in experimental models of sepsis. C57/BL6 mice were used in experimental sepsis protocols cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)‐induced severe and mild sepsis. Glucosamine treatment (300mg/Kg, i.v. 30 min. before the sepsis induction) acutely increased vascular and spleen O‐GlcNAc levels and increased survival of mice with LPS‐induced sepsis (50%) and CLP sepsis (40%). In mice with LPS‐induced sepsis, glucosamine also reduced neutrophil migration to the peritoneal cavity (severe LPS sepsis, p<0.05; mild LPS sepsis, p<0.01), myeloperoxidase (MPO) activity of lung neutrophils (severe LPS sepsis, p<0.01; mild LPS sepsis, p<0.001) and aortic IL‐1beta mRNA expression (mild LPS sepsis, p<0.01). In the CLP model, glucosamine reduced MPO activity of lung neutrophils (p<0.05). These results show that glucosamine‐induced acute increases of O‐GlcNAc levels increase survival in the CLP and LPS experimental models of sepsis. This study suggests that the O‐GlcNAc pathway represents a potential target in sepsis‐related systemic inflammatory responses.Grant Funding Source: CNPq, CAPES and FAPESP
Animal model for assessment pro‐inflammatory response of fat tissue and liver induced by prenatal stress and diet high in sugar and fat (840.14)
Authors: Bezpalko Lyudmyla , Zayachkivska Oksana , Havryluk Elena 
Published: June 2021

Life style diseases (LSD) recognized as one of the non‐inflectional epidemic worldwide and LSD‐related liver pathology is common distributed. Recent data had shown intrauterine (prenatal) programming of adult metabolic phenotype. No study has explored potential interaction between maternal diet high in sugar and fat and stress on adipocytokine secretion and changes of liver functions in adulthood.The aim: To create a animal model of prenatal stress in rats to examine role of maternal stress and diet on activities of adipose tissue and hepatocellular organization in the offspring which can provide basis in treating hepatopathologies in preclinical and clinical settings.We used rat offsprings of mothers which had during all period of pregnancy social stress with (1) ad libitum access to 30% saccharose (Kozar, 2009); (2) high‐fat diet (to 45% kcal, Lintermans, 2009); and (3) binary those factors vs control. Scoring lesion (LI), vascular indexes (VI) by fat, liver histomorphology, IL‐1β, GRO/CINC‐1, leptin, adiponectin by ELISA.Relative to the control the most changes were determined in the 3d group: histologically ‐ both in the visceral fat tissue and liver appeared the cell reorganization with signs of inflammation, rise IL‐1β (217%), GRO/CINC‐1 (99%), leptin (79%) levels and decreased of adiponectin (41% ); rise of ratio Leptin/Adiponectin was in twice.Conclusion: Taken together maternal stress and high sugar‐fat diet reveal both prenatal effect on prenatal programming of offspring adipocyte secretion with liver proinflammatory changes. This animal model can be useful for follow up pharmacology investigation of pro‐inflammatory and metabolic state in adulthood.
Cytotoxic effects of selective serotonin‐ and serotonin‐norepinephrine reuptake inhibitors on human metastatic breast cancer cell line, MCF‐7 (842.3)
Authors: Bavadekar Supriya , Panchal Palak , Hanbashi Ali , Vansal Sandeep 
Published: June 2021

Current evidence suggests that some antidepressants possess growth‐inhibitory effects against a number of cancer cell lines. The present study evaluated seven of the most commonly prescribed antidepressants in the US for cytotoxic effects on MCF‐7 breast cancer cells. These included selective serotonin reuptake inhibitors (sertraline, fluoxetine, paroxetine, citalopram, escitalopram) and serotonin‐norepinephrine reuptake inhibitors (venlafaxine, duloxetine). Viability was determined after 24 h using the XTT cell proliferation assay. All test agents inhibited cell growth in a concentration‐dependent manner. Sertraline (IC50~16 µM) was the most potent, followed by equipotent paroxetine, duloxetine, and fluoxetine (IC50~31‐36 µM), while citalopram, escitalopram, and venlafaxine were significantly weaker. The lead compound, sertraline, induced apoptosis, as evidenced by morphological changes, phosphatidylserine externalization, and poly(ADP‐ribose) polymerase (PARP) cleavage. Future experiments are aimed towards identifying the binding site(s) for sertraline and further elucidating the signal transduction pathway(s) involved in the cytotoxic effect. In summary, the high sensitivity shown by the four most potent agents, and especially sertraline, in inhibiting MCF‐7 growth suggests that these agents should be evaluated further for potential use in anti‐breast cancer therapy.Grant Funding Source: This work is supported by the Division of Pharmaceutical Sciences at Long Island University.