bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calorie Restriction Delays the Aging of Saccharomyces cerevisiae by Improving Complex III Activity via Glutathione Peroxidase 2 (Gpx2)
Authors: Hurtado-Villagómez Ana Victoria , Olmos-Orizaba Eridani , Saavedra - Molina Alfredo , Rodriguez-Orozco Alain Raimundo , Calderon-Cortes Elizabeth , Cortes-Rojo Christian 
Published: April 2020

Comparative studies among organisms of different species of the same genus have found that long ‐ lived species contains polymorphisms in the sequence of the cytochrome b (Cyt b) subunit of the complex III leading to lower ROS production, which has been suggested to contribute for longer lifespans. Cyt b is a highly hydrophobic protein that depends on cardiolipin for its function. Cardiolipin peroxidation impairs electron transfer at the cytochrome b and enhances ROS by inducing electron leak. Cardiolipin peroxidation is repaired in mitochondria by Gpx2. Calorie restriction, the only non‐genetic manipulation increasing the lifespan, induces a hormetic response enhancing the activity of antioxidant systems like Gpx. Thus, it is feasible to hypothesize that calorie restriction increases longevity in yeast by preserving complex III activity and electron transfer in the Cyt b in a Gpx2 – dependent manner. Calorie restriction was induced in yeast with 0.05% glucose in YPD medium. YPD 0.05% extended the chronological lifespan of yeast in comparison with YPD medium with standard 2% glucose. Calorie restriction also improved complex III activity in aged yeasts and enhanced the reduction of Cyt b. The beneficial effects of calorie restriction on chronological lifespan, complex III activity and Cyt b reduction were lost in a GPX2Δ yeast mutant. These results suggest that preservation of complex III activity by enhanced electron transfer at Cyt b might be another mechanism by which calorie restriction extends longevity, which might be related with lower ROS generation and protection of cardiolipin against oxidative damage induced by aging.Support or Funding InformationThis work was supported by a grant from Programa de Investigación 2019, Coordinación de la Investigación Científica ‐ UMSNH (CCR).
Effects of the Bioflavonoid Quercetin on TLR4 Expression and NFKb activation in A375 Melanoma Cells
Authors: Hawley Cassidy , Mankins Claire , Byrd Shere K. 
Published: April 2020

Early research indicates that quercetin, a bioflavonoid, seems to limit cancer progression through the down regulation of toll‐like receptor 4 (TLR4). Many cancers, including melanoma, upregulate expression of TLR4 which appears to be associated with cell survival and proliferation. The purpose of this study is to examine TLR4 expression, downstream signaling and changes in target gene expression that may contribute to quercetin’s anti‐proliferative properties. Cells were treated with 100 uM quercetin, vehicle control (DMSO), or no treatment for 24 hours. NFKb activation was quantified by differential centrifugation of cytosolic and nuclear fractions of treated cells by immunoprecipitation and Western blotting. TLR4 was evaluated with immunoblotting. We found that quercetin treated cells had 15% higher NFKb nuclear fraction than the cells with no or vehicle only treatment. TLR4 was, however, effectively downregulated by quercetin treatment. These findings are similar to those seen pancreatic cancer and some other cell models. It appears that this bioflavonoid may have different targets and effects in different types of cancer cells, making it necessary to understand its differential mechanisms of action.Support or Funding InformationSupported by the NIH Common Fund, through the Office of Strategic Coordination, Office of the NIH Director with the linked awards: TL4GM118992, RL5GM118990, UL1GM118991 and by Fort Lewis College MARC‐USTAR.
Bile Acid Membrane Receptor TGR5 Inhibits Alcohol‐Induced Liver Steatosis
Authors: Fan Mingjie , Liu Yanjun , Tu Jui , Wang Yangmeng , Jin Lihua , Huang Wendong 
Published: April 2020

Alcoholic liver disease (ALD) is one of the leading causes of liver failure in the world. It progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized with hepatic inflammation. Chronic ASH will result in fibrosis, cirrhosis and hepatocellular cancer (HCC) eventually. However, very few treatment options for ALD are available currently. Therefore, there is an urgent unmet medical need to better understand the molecular mechanisms underneath the development of ALD and develop effective treatment approaches. Bile acid signaling in the liver‐gastrointestinal tract axis is important for the integrated regulation of lipid, glucose, and energy metabolism. Dysregulated bile acid signaling is associated with ALD due to the fact that alcohol significantly alters bile acids pool and composition in humans and rodents. G‐protein‐coupled bile acid receptor, Gpbar1 (TGR5), is a membrane bound bile acid receptor. It is more broadly expressed, but its hepatic expression is limited to Kupffer cells, macrophages and sinusoidal endothelial cells. Little information regarding the effects of TGR5 in the pathological development of ALD has been reported before. In this study, we use C57BL/6(WT) and TGR5 knockout (TGR5−/−) mice to study the potential role of TGR5 in alcohol‐induced liver disease. Mice were challenged with chronic 5% ethanol feeding (10 days) plus a binge dose of alcohol by oral gavage (5 g/kg body weight) or with acute high dose alcohol gavage. The results showed that the liver/body weight ratio was increased in both WT and TGR5−/− ethanol fed mice, while it was significant higher in ethanol fed TGR5−/− mice than WT mice. The liver injury marker serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were both increased. Alcohol feeding altered gene expression in bile acid homeostasis. The hepatic triglycerides were upregulated almost 30% higher in TGR5−/− mice than WT group. The haematoxylin Eosin (H&E) and Oil Red O staining showed more fat vacuoles in the liver of ethanol fed TGR5−/− mice than that in WT mice. We also treat the mice with a novel potent TGR5 agonist ligand and found protective effects on ALD in WT but not TGR5−/− mice. Collectively, these results suggest that TGR5 may prevent the development of ALD and represent a novel target for ALD treatment.Support or Funding InformationCity of Hope Departmental Internal funding
Teaching Difficult Physiological Concepts to the Medical Students Using Minicases, Educreations and Mentimeter
Authors: Ahmad Kashif Adil 
Published: April 2020

PurposeIt is a consensus in medical schools that basic science courses is offered in a compressed curriculum, and medical students have difficulty in retaining essential basic science concepts. It is well established that medical, nursing, and healthcare schools use various pedagogical methods to deliver physiology curriculum. Our abstract focuses on medical education, it is always challenging for medical students to retain a plethora of physiology and pharmacology information. These concepts are considered high yield for passing standardized exams. We have shown the effectiveness of new modern tools in medical education that enhances the student learning experience.
1MethodsIn collaboration with the students, we inquired and collected feedback and created a grid of physiological concepts that students find difficult to understand, examples include current multiplication in renal physiology, flow volume loops in respiratory.We then planned three modes of content delivery methods. First, we designed short videos using novel technological tools like educreations clarifying those concepts. The students could view these videos at any time, anywhere, and on any device. We then offered mini‐cases in small groups that promoted higher‐level thinking on Bloom’s Taxonomy, for example, a case on diabetes insipidus that touched upon functions of ADH and integrated clinical reasoning. Finally, using Mentimeter (a novel audience response system), we conducted a short quiz as an interactive readiness experience for our students. The informal 15‐minute quiz was an effective way for students to gauge their performance. In this live session, the basic science instructor(s) were tasked to refresh, review, and validate physiology/pharmacology concepts with the students.Results/OutcomesAccording to our satisfaction surveys, students appreciated digital cognition. The survey response rate was 75% (n=24/32). More than 80% of students found the active learning sessions met their expectations or far exceeded their expectations. Examples of student narratives include, “The learning checkpoints and engaging activities with mini‐cases were good. It exceeded my expectations because I didn’t expect dedicated time to be given to that, but I am glad it did and would like to see similar things like this done in the future.” “The dedication of the instructor to providing learning materials in the forms of videos, readings, and mini‐lectures was a huge strength of the curriculum.”DiscussionWe conclude that our method of content delivery will provide an ideal opportunity for all students to learn the importance of contextual and difficult physiological concepts. The approach can help in identifying knowledge gaps and can serve a useful model for curricular delivery in medical schools, nursing, or any healthcare school that would like to promote critical thinking with a deeper understanding of physiology integrated with clinical science.
Zonulin antagonist protects against tight junction disruption by Pseudomonas aeruginosa in airway epithelial cells
Authors: Kalsi Kameljit Kaur , Jackson Sonya , Baines Deborah Louise 
Published: April 2020

Zonulin is known as a regulator of barrier function in both epithelial and endothelial cells in the intestine and kidney by acting through EGFR (epidermal growth factor receptor) and PAR2 (Proteinase activated receptors) to cause the dissociation of ZO‐1 from occludin and claudin‐1 from the cell junctions. Respiratory infection is characterized by increased lung permeability caused by the reduction in the abundance and/or distribution of proteins at the tight junction. Here the effect of the zonulin antagonist, larazotide acetate (LA) on airway epithelial cell barrier function after the addition of lipopolysaccharide (LPS) from Pseudomonas aeruginosa or undiluted P.aeruginosa filtrate isolated from an overnight culture was investigated. Two human airway epithelial cell models were used, H441 cells grown at air‐liquid interface and 16HBE14o‐cells grown as submerged monolayers. Cells were incubated with 10 μg/ml LPS and 12 mM larazotide acetate. Transepithelial electrical resistance (TEER) and permeability was measured after 1h and 6h. TEER was decreased with LPS which was prevented by LA, (p<0.05, n=3) LPS vs LPS/LA at 1 hour. Permeability was increased with LPS after 6h (p<0.05, n=3) LPS vs control. Cells were immunostained for ZO‐1 and E‐cadherin, LPS caused the disappearance of ZO‐1 staining at the apical surface which was conserved with LA. E‐cadherin localization did not change with either LPS or LPS/LA treatment. Total protein abundance assessed by western blot showed no changes. Exposure of 16HBE14o‐ cells to P.aeruginosa filtrate for 24 h lead to a 61% decrease in TEER compared to control (p<0.0001, n=3). P.aeruginosa filtrate/LA increased TEER by 39% (p<0.02, n=3). Tight junction localization of E‐cadherin and claudin‐1 were both disrupted with P.aeruginosa filtrate while incubation with LA attenuated this rearrangement. This study shows that larazotide acetate helped to counteract the damage to tight junctions caused by LPS and P.aeruginosa filtrate, this supports a role for zonulin as a regulator of lung epithelial barrier function.Support or Funding InformationFunded by Astra Zeneca
Remediation of Nitrate in Drinking Water and Accumulation of Lipids using Microalgae
Authors: Hankore Wihib D. , Behrens Mark , Black Paul , DiRusso Concetta 
Published: April 2020

The use of fertilizers in agriculture, and especially nitrogen to improve crop yield has resulted in the accumulation of high levels of nitrates in the groundwater (wells) throughout the mid‐western US states. This can lead to high levels of nitrates in drinking water, which exceeds the Safe Drinking Water Act, which the EPA limits at 10 mg/L. Drinking water containing nitrate levels above 10 mg/L is associated with significant health risks, particularly to unborn infants, as it can cause blue‐baby syndrome, a condition caused reduced capacity of hemoglobin to carry oxygen. Our laboratory has been employing microalgae to remediate nitrates to reduce this burden on water supplies. Two of the algal strains we have used were able to reduce Bold Basal Media (BBM) level nitrate (42mg/L) down to below 1 mg/L in 4 days, with an optical density (OD550) absorbance of around 3.0. In addition to remediating nitrate from contaminated sources, these microorganisms also accumulate lipids (triglycerides) under certain nutrient conditions and have been promoted as a feedstock for biofuels. Our lab has discovered several small compounds including WD30030 and WD20067 that induce lipid accumulation in algae without reducing growth and biomass in Chlamydomonas reinhardtii. In the present studies, we evaluated the impact of the compounds on several algal strains that have shown good growth in large bioreactors, Coccomyxia subellipsoidea – C169, Scenedesmus acutus f. alternans (UTEX B72), Chlorella kessleri (UTEX 2229) and Bumilleriopsis filiformis. Both nitrate removal and lipid accumulation during growth were monitored to assess whether or not these organisms can be used to couple nitrate remediation to production of high value lipid products.Support or Funding InformationNebraska Department of Economic Development and Vestal W2O, LLC
Angiotensin‐(1‐7) Actions in Animal Models of Metabolic Syndrome: a Systematic Review
Authors: Cordeiro Beatriz , Hilgemberg-Junior Romel , Guimaraes Priscila 
Published: April 2020

This systematic review aims to collect all available data of Ang‐(1‐7) in animal models to study metabolic syndrome (MetS). The following electronic bibliographic databases have been searched: PubMed, EMBASE, Web of Science, and Scopus. The full search strategy was based on the search components “animal models”, “metabolic syndrome” and “angiotensin‐(1‐7)”. No publication date or language restrictions have been applied. The protocol of this study is available online in PROSPERO. The comprehensive search retrieved a total of 2056 citations (EMBASE, n = 816; PubMed, n = 285; SCOPUS, n = 290; Web of Science, n = 665). All citations were saved into one file in reference software. After removing duplications (n = 891), a total of 1419 citations were screened considering title and abstract, resulting in 149 citations selected as potentially relevant articles. These were then screened considering the full text content, resulting in 54 citations for data extraction. The other citations were either duplications (n = 4), conference abstracts (n = 66), or did not match inclusion criteria for disease and/or intervention (n = 25). Data extraction revealed that 31 of 54 studies, besides evaluating metabolism, have performed in vivo and/or ex vivo protocols to analyze the effects of increasing Ang‐(1‐7) availability (n = 27) or Mas receptor blockade (n = 4) on cardiovascular system. Among the other 23 citations that did not study cardiovascular parameters, 20 evaluated Ang‐(1‐7) effects on metabolism, and 3, the blockade or knockout of Mas recector. Outcomes are still being extracted and categorized for reporting. All database searches have been performed in July, 2019. This systematic review may gather all available data of Ang‐(1‐7) in animal models to study MetS, based on original full text articles, and categorize it by type of interventions, animal models, MetS induction method, and outcome measures. These results may contribute to highlight the efficacy of Ang‐(1‐7) on MetS risk factors as well as possible related gaps in the literature in this concern.Support or Funding InformationFAPEAL, CAPES, CNPq
Effects of exercise training on metabolic and cardiovascular dysfunctions in offspring of fructose animals: role of cholinergic anti‐inflammatory reflex.
Authors: Dias Danielle Silva , Dos Santos Camila Silva , Araujo Amanda , Ferreira Maycon , Shecaira Tânia , Carmo Gabriel , Bernardes Nathalia , Irigoyen Maria Cláudia , De Angelis Kátia 
Published: April 2020

AimTo evaluate the effects of aerobic ET on metabolic and cardiovascular parameters in offspring of fructose‐consuming animals, testing the role of cholinergic anti‐inflammatory reflex in this condition by splenectomy.MethodsOffspring of Wistar genitor rats treated with fructose or placebo (water) were divided into 4 groups: sedentary‐water (W), sedentary‐fructose (F), trained‐fructose (TF) and trained‐splenectomized‐fructose (TSF). Fructose overload (10%) was started 30 days after weaning only for the parents and continued until the end of lactation. The offspring received standard feeding and 30 days after weaning the spleen was removed (splenectomy) and the ET was started on treadmill (1h/d, 5d/week, 4 weeks, moderate intensity). After 30 days, the glycemia, blood triglycerides (TG) and insulin tolerance were evaluated. Blood pressure (BP) and heart rate (HR) signals were directly recorded in awake animals through an acquisition system.ResultsAlthough no differences in glycemia and insulin tolerance were observed, the TSF group showed an increase in TG compared to W, F and TF groups (166 ± 12 vs. 100±6; 113±11; 110±4 mg/dL). Regarding cardiovascular changes, the F group had increased systolic blood pressure (SBP) compared to W group (F: 127±4 vs. W: 117±2 mmHg). ET prevented the increase in SBP (TF: 118 ± 2 mmHg); however, this benefit was not observed in the TSF group (129±5 mmHg). In addition, diastolic BP was higher in the TSF group (100±6 mmHg) compared to W and TF groups (91 ± 3 and 87 ± 2 mmHg). There was no difference in HR between the groups studied. BP variability was increased in F group in relation to TSF group.ConclusionThe consumption of fructose by parents induced early BP changes in offspring, which were prevented by exercise training. In addition, splenectomy abolished the cardiovascular benefits of ET in offspring of fructose rats, suggesting participation of the anti‐inflammatory cholinergic reflex in these adaptations.Support or Funding InformationFAPESP: 2018/17183‐4, CNPq (157746/2018‐6) and UNINOVE
Ultra‐processed Food Consumption and Vascular Health
Authors: Smiljanec Katarina 
Published: April 2020

Ultra‐processed (UP) foods are ready‐to‐eat foods formulated from industrial sources of dietary energy and nutrients, containing little or no whole foods. These products are typically high in saturated fats, added sugar, salt, and food additives, and low in protein, fiber, and micronutrients. UP foods are associated with an increase in energy intake (EI), weight gain, obesity, and cardiovascular disease. The objective of this study was to test the hypothesis that UP food consumption is associated with increased blood pressure (BP), arterial stiffness, and pressure wave reflection. Habitual dietary intake was assessed via 3‐day food records in 22–45 year old non‐hypertensive adults. Food items were categorized to non‐processed and/or minimally processed (NP) and UP groups by using the NOVA system of food classification. Bivariate and partial Pearson correlation was used to identify relations between NP and UP foods with systolic (SBP) and diastolic BP (DBP), pulse wave velocity (PWV), and augmentation index normalized for heart rate at 75 beats per minute (AIx75). Thirty eight healthy subjects (17M, 21F; 29±7 yrs; BMI 23.9±3.3 kg/m2) were included in the study. Average UP food consumption was 45±18% of daily EI. UP food consumption was positively associated with AIx75 (r=0.45, p<0.001), and trended to be positively associated with peripheral SBP (r=0.32, p=0.05) and peripheral DBP (r=0.29, p=0.07). When controlled for BMI, UP food consumption was positively associated with peripheral DBP (r=0.47, p=0.02), AIx75 (r=0.50, p=0.01), central SBP (r=0.44, p=0.03), and remained trending with peripheral SBP (r=0.40, p=0.05). When only women were analyzed, UP food consumption was positively associated with peripheral SBP (r=0.48, p=0.03), central SBP (r=0.57, p=0.03), AIx75 (r=0.54, p=0.01), and trended to be positively associated with peripheral DBP (r=0.41, p=0.06), even after controlling for BMI. There were no associations with UP food consumption and BP, PWV, or AIx75 in men. These findings suggest that UP food consumption is associated with increased BP and pressure wave reflection in healthy individuals and that these relations are more pronounced in women.Support or Funding InformationSupported by NIGMS P20GM113125
The Effect of EGF Inhibition on Diurnal Variation of Blood Pressure in Mice
Authors: Arroyave Juan Sebastian , King-Medina Keyona N. , Lim Heeju , Hoover Robert S. 
Published: April 2020

There are 78 million adults in the United States, who have hypertension also known as the “silent killer” because most individuals are unaware of their diagnosis. High blood pressure (BP) is a serious medical condition that serves as risk factor for cardiovascular disease (CVD), diabetes, and chronic kidney disease (CKD). Blood pressure normally declines about 10% during sleep. This nocturnal decline in blood pressure is called “dipping”. Studies have demonstrated that an attenuated decline in nocturnal blood pressure (“non‐dipping”) is associated with increased cardiovascular risks. Investigations by our group and others have demonstrated an effect of the epidermal growth factor (EGF) on sodium transport proteins and blood pressure. However, an association between EGF and “dipping” has not been described. We hypothesized that the inhibition of EGF will attenuate the sleep time (daytime for mice) decline of BP in mice. Using radio‐telemetry, in five male mice ages 6–7 weeks old, we collected the systolic blood pressure (SBP) measurements over 24‐hours daily for two weeks. These animals received a low Na+ diet (0.4% Na chow) for 6 days and high Na+ diet (4% Na chow) for 8 days. Only the experimental (E) group (n=3) received gefitinib (an EGF receptor tyrosine kinase inhibitor) at a regimen of 100 mg/kg/d given orally while the control (C) group (n=2) received a placebo. The change in SBP for sleep (9am–9pm) versus awake (9pm–9am), while receiving low salt diet (0.4% Na chow), showed the experimental group had less of a decrease in their SBP compared to the control group (E group: −9.7 ± 0.016 vs. C group: −14.4 ± 0.34 mmHg, p<0.001). The change (delta, Δ) in SBP was 4.7 mmHg, p<0.001 where the control group had a greater decrease in their SBP. When increasing the dietary Na+ intake by giving the high salt diet (4% Na+ chow), once again the experimental group demonstrated an attenuation of their ability to lower their SBP during sleep time compared to the control group (E group: −7.3 ± 0.18 vs. C group: −13.5 ± 0.38 mmHg, p<0.001). Here the Δ is 6.1 mmHg, p<0.001, which shows that the control group maintained a greater decrease in their resting SBP compared to the experimental group. Overall, our results suggest that inhibition of EGF leads to decreased dipping in SBP regardless of the dietary Na+ intake. This effect is greater with high Na+ in the diet. Our data is the first to suggest that EGF may play a role in the nocturnal dipping of blood pressure. This could have potential implications for hypertension‐related cardiovascular disease.Support or Funding InformationNIH T32:5T32DK007656‐28 (King‐Medina) and VA Merit Awards: I01BX002322‐01 (Hoover)