bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Obesity on Vascular Dysfunction Following Hemorrhagic Shock
Authors: Walker Ashley E. , Cole Jazmin , Kumaran Sahana Krishna , Zhuang Xinhao , Wolf Julia R. , Henson Grant D. , McCully Belinda H. 
Published: April 2020

Obesity is associated with higher rates for complications after traumatic hemorrhage, including higher incidence of multiple organ failure, thrombosis, and mortality. These adverse events are associated with prolonged tissue hypoperfusion, hypercoagulability, and edema that reflect profound vascular damage. However, the combined impact of obesity and traumatic hemorrhage on vascular function is not well understood. Therefore, we sought to determine the impact of diet‐induced obesity on vasoconstrictor and vasodilator properties of arteries before and after hemorrhagic shock.Male Sprague‐Dawley rats were fed a control (CON; 13.5% kcal fat, n=10), moderate fat (MF, 33% kcal fat n=9) or high fat (HF, 60% kcal fat, n=10) diet for 6–8 weeks. Hemorrhagic shock was induced by laceration of a mesentery artery and a Grade V splenic injury under anesthesia, and a period of hypotension (mean arterial pressure = 30–40 mm Hg) was maintained for 30 minutes. We assessed vasoconstrictor and vasodilator properties in isolated mesenteric arteries harvested before and after hemorrhagic shock. Before hemorrhage, peak norepinephrine (NE) vasoconstriction was higher in CON rats (78±4%) versus HF (62±5%, p=0.01), while MF rats exhibited a peak NE vasoconstriction not different from either groups (71±3%, p>0.05 vs CON and HF). Baseline endothelium‐dependent dilation, assessed as the maximal response to acetylcholine, was not different between groups (CON: 97±1%, MF: 88±4%, HF: 92±3%, p=0.08). Hemorrhage lowered the peak NE vasoconstriction (post: 61±8%, p=0.05) and endothelium‐dependent dilation in CON rats (post: 90±2%, p<0.001), but had no effect on NE vasoconstriction and endothelium‐dependent dilation in MF and HF rats (p>0.05 vs pre‐hemorrhage). Endothelium‐independent dilation, assessed as the response to sodium nitroprusside, was similar pre‐ and post‐hemorrhage in all groups (p>0.05).In conclusion, we find traumatic hemorrhage induces vascular dysfunction characterized by a reduced vasoconstrictor response and impaired endothelial function, but only in rats fed a normal chow diet. While obesity results in vascular dysfunction at baseline, it does not contribute to a further worsening of function after traumatic hemorrhage.Support or Funding InformationFunded by a UO‐OHSU Collaborative Seed Grant
miR‐3074‐3p promotes myoblast differentiation by targeting Cav1
Authors: Lee Bora 
Published: April 2020

Muscle fibers are generally formed as multinucleated fibers that are differentiated from myoblasts. Several reports have identified transcription factors and proteins involved in the process of muscle differentiation to date, but the role of microRNAs (miRNAs) in myogenesis is still unclear. Here, comparative analysis of the miRNA expression profiles in mouse myoblasts and gastrocnemius (GA) muscle uncovered miR‐3074‐3p as a novel miRNA showing markedly reduced expression in fully differentiated adult skeletal muscle. Interestingly, elevating miR‐3074‐3p promoted myogenesis in C2C12 cells, primary myoblasts, and HSMMs, resulting in increased mRNA expression of myogenic makers such as Myog and MyHC. Using a target prediction program, we identified Caveolin‐1 (Cav1) as a target mRNA of miR‐3074‐3p and verified that miR‐3074‐3p directly interacted with the 3′ untranslated region (UTR) of Cav1 mRNA. Consistent with the findings in miR‐3074‐3p‐overexpressing myoblasts, knockdown of Cav1 promoted myogenesis in C2C12 cells and HSMMs. Taken together, our study suggests that miR‐3074‐3p is a positive regulator of myogenic differentiation by targeting Cav1.Support or Funding InformationWe thank S.‐Y. Kim (Genome Editing Research Center in KRIBB) for the advice and discussion in the miRNA analysis. This study was supported by grants from the Bio & Medical Technology Development Program (2017M3A9D8048708) of the National Research Foundation (NRF) funded by the Korean government (Ministry of Science and ICT), the UST Young Scientist Research Program through University of Science and Technology (2019YS07) and the KRIBB Research Initiative Program.
Long‐Term Intake of Capsiate Increases Fat Accumulation according to Reduced‐Energy Expenditure, which Is Occurred by Increased‐Immobility in Diet‐Induced Obese Mice but not in Trained.
Authors: Hwang Deunsol , Kim Jisu , Seo Jongbeom , Lim Kiwon 
Published: April 2020

PurposeHaving a similar weight‐loss effect which is occurred by the sympathetic nervous stimulation of capsaicin, capsiate (CAP) began to spotlight because of its much less pungency than capsaicin’s. However, previous studies have tended to focus on short‐term (to 2 from 4 weeks) effect of CAP with normal diet. Therefore, the purpose of this study was to identify the effects of long‐term CAP intake and high‐fat diet (HFD) on energy expenditure and fat accumulation. And we also investigated whether there was a synergistic effect on fat accumulation when exercised together.MethodsThe male 8‐week‐old ICR mice were divided into 4 groups. Sed0 (sedentary; non‐trained), Sed10 (sedentary and 10 mg/kg of CAP), Tr0 (moderate intensity‐trained) and Tr10 (moderate intensity‐trained and 10 mg/kg of CAP). All mice freely accessed to water and HFD.Treadmill training was conducted with 5times a week for 8 weeks. The exercise intensity was increased from 20 min at 13 m/min to 60 min at 16 m/min while maintaining the 8° slope. The Tr groups were administrated each supplement 30 minutes before training. Tail‐suspension test was performed by suspending a mouse from horizontal bar. Mouse was suspended by its tail for 6min, and the immobility time was measured during the last 5min, with the first minute ignored to allow for habituation.ResultsLong‐term intake of CAP did not significantly change the body weight gain in the both sedentary and trained group. However, the total food intake was significantly lower in the Sed10 than in the Sed0 and reversely greater in the Tr10 than in the Tr0. Interestingly, the total abdominal fat was significantly higher in the Sed10 than in the Sed0 and the training showed a tendency to reverse this result but there was no significant difference within the Tr group. From the resting metabolic rate results, the total energy expenditure was slightly lower in the Sed10 than in the Sed0 but there was no significant difference within both Sed and Tr group. However, there was significant difference between the Sed10 and the Tr10 but not between the Sed0 and the Tr0. From the tail suspension test results, the immobility time was significantly longer in the Sed10 than in the Sed0 and there was no significant difference within the trained group. But the BDNF protein level in the hippocampus was no different.ConclusionIn summary, these results show that long‐term intake of CAP with HFD increased fat accumulation according to reduced‐energy expenditure, which seemed to be occurred by immobility. But the moderate intensity‐exercise reversed these results. Therefore, if CAP is used to increase energy expenditure over long periods of time, we suggest that exercise and/or dietary control should be properly combined. Furthermore, these findings provide a slight insight that long‐term intake of CAP with HFD could be assessed by the neuropathological approach.
Description and outcomes of a baccalaureate level clinically oriented gross anatomy course
Authors: Thompson Andrew R. , Giffin Bruce F. 
Published: April 2020

While many universities offer some type of anatomy course at the baccalaureate level, training in clinically oriented human anatomy with a dissection component has traditionally been restricted to advanced degrees in the medical, dental, and veterinary fields. The University of Cincinnati College of Medicine (UCCOM) offers a Bachelor of Science degree in Medical Sciences to train students with a strong interest in pursuing a career in healthcare. In 2018, a human gross anatomy course was added to the curriculum that includes both lecture and lab (dissections) components and focuses on clinically relevant anatomy and medical imaging. The purpose of this study is to 1) describe the development of the course and 2) to determine if undergraduate students are able to perform at a comparable level to medical students in the content area of clinical anatomy. The latter goal was achieved by blueprinting examinations related to the limbs for the undergraduate and medical school courses at UCCOM using Bloom’s taxonomy and then comparing performance between the two groups of students. A total of 70 and 39 lecture‐examination questions for undergraduate and medical students were analyzed, respectively. Practical examinations were also considered for the limbs region.Results demonstrate that undergraduate students perform almost identically to medical students on lecture examination questions that target the first three levels of Bloom’s Taxonomy (remember, understand, and apply). Application level questions are, however, more challenging for undergraduate students as they scored ten percent lower, on average, compared to medical students. On practical examinations, undergraduate students averaged seven percent lower than medical students. Higher‐order practical examination questions are more challenging for undergraduate students as they averaged nearly 15% lower than medical students. The average discrimination index of higher‐order practical exam questions was also larger in the undergraduate course at 0.55 compared to 0.27 with medical students. Overall, these results suggest that undergraduate students have the capacity to perform at a comparative level to medical students on advanced, clinically‐relevant gross anatomy material. However, some undergraduate students may be less equipped to handle higher‐order assessment questions.
TRPV4 mechanosensing regulates normal human lung fibroblast migration
Authors: Rahaman Suneha G. , Goswami Rishov 
Published: April 2020

Fibroblast migration is recognized as a critical process in wound healing and fibrosis. Although the influence of both a biomechanical signal (e.g., matrix stiffness) and a biochemical signal (e.g., transforming growth factor beta1; TGFbeta1), are essential for fibroblast migration, the molecular mechanisms by which migratory signals are transduced are poorly understood. Here, we report that TRPV4, an ion channel in the transient receptor potential vanilloid family, and which is a mechanosensor, is required for both TGFbeta1‐ and matrix stiffness‐induced migratory response (chemotaxis, durotaxis, scratch wound closure, and adhesion) of normal human lung fibroblasts. Furthermore, TRPV4 antagonism by a selective small molecule inhibitor abrogates calcium influx, stiffness‐induced stress fiber formation, and both TGFbeta1 and matrix stiffness‐induced focal adhesion kinase (FAK) activation. Moreover, we show that TRPV4 activity is required for stiffness‐induced force generation in migrating fibroblasts as determined by Traction Force Microscopy analysis. Taken together, these results suggest that TRPV4 and FAK interact to drive fibroblast migration by potentiating TGFbeta1 signaling in a manner dependent on matrix stiffness. Successful manipulations of the TRPV4 activity may be a novel therapeutic approach to the treatment of fibrotic diseases.Support or Funding InformationThis work was supported by NIH (1R01EB024556‐01) and NSF (CMMI‐1662776) grants.
Ramipril Blunt Glycerol‐induced Acute Renal Failure in Rats Through its Anti‐apoptosis, Anti‐inflammatory, Anti‐oxidant, and Renin‐inhibiting Properties
Authors: Adedapo Adeolu Alex , Ehizogie Osaretin Ruth , Falayi Olufunke Olubunmi , Oyagbemi Ademola Adetokunbo , Ogunpolu Blessing Seun , Omobowale Temidayo Olutayo , Oguntibeju Oluwafemi Omoniyi , Yakubu Momoh Audu 
Published: April 2020

Acute Kidney Injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days and causes a buildup of waste products in the blood making it hard for the kidney to keep the right balance of fluid in the body. It affects other organs such as the heart, brain and lungs (Schrier et al., 2004). Renal tubular damage is a pathological characteristic of AKI. Currently, animal models of glycerol‐induced AKI are widely used [Mousleh et al 2018]. Glycerol injection into the muscle causes the release of myoglobin and other muscle contents into the circulation, ultimately resulting in AKI. Studies have demonstrated that the pathogenesis of glycerol‐induced AKI involves myoglobin toxicity [Gburek et al 2003; Reeder and Wilson 2005], reactive oxygen species (ROS) [Wu et al 2017], inflammation [
Al Asmari et al 2017], apoptosis [Wang et al 2011] and redox‐active iron [Wu et al 2017].In this study ramipril and pioglitazone (reference drug) were evaluated for their potential therapy in glycerol‐induced AKI in rats. Twenty animals divided into four groups of five animals per group were used. Group I served as control while group II received glycerol on day 8 only. Groups III and IV were administered with pioglitazone and ramipril for 7 days respectively and on day 8 received glycerol. On day 9 blood samples were collected for serum biochemical analysis of markers of oxidative stress, enzymatic and non‐enzymatic antioxidants, creatinine and blood urea nitrogen. Animals were sacrificed thereafter; and kidney tissues were harvested for histopathology and immunohistochemistry. Expression of caspase 3, renin receptor, NK‐KB, and KIM‐1 were carried out.Results from this study show that ramipril and pioglitazone significantly inhibited markers of oxidative stress while also significantly increased the levels of enzymatic and non‐enzymatic anti‐oxidant markers. These drugs caused decreased levels of creatinine and BUN. Histopathologically, there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, but the ramipril treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group.This study thus showed that ramipril and pioglitazone have nephroprotective effect and thus has ability to blunt acute kidney injury through their anti‐inflammatory, anti‐apoptosis, anti‐renin and anti‐oxidant properties.Support or Funding InformationThis study was supported with a grant (TETFUND/DESS/NRF/UI IBADAN/STI/VOL. 1/B2.20.11) received from the National Research Foundation of the Tertiary Education Trust Fund (TETFUND), Abuja, Nigeria.
Strong Antimicrobial Activity of Hydroxamic Acids and Newly Synthesized Derivatives
Authors: Antunes Daniel Ignacio D. , Aslanian Robert G. , Aqani Omar , Desai Harshal , Bendaoud Meriem 
Published: April 2020

Antibiotic resistant pathogenic bacteria are a growing worldwide health concern according to the Centers for Disease Control and Prevention. These bacteria are responsible for most of the infectious diseases and healthcare‐associated infections in hospitals (HAIs). The need for new therapeutic approaches using novel antimicrobial compounds is becoming vital as the number of infections caused by antibiotic resistant strains of bacteria such as Staphylococcus aureus and Staphylococcus epidermis has drastically increased. The focus of this study is to test newly designed and synthesized therapeutic agents for antimicrobial properties. Several hydroxamic acids and analogs synthesized by the Chemistry Department at New Jersey City University were tested for antibacterial activity against eight ATCC strains of human and plant pathogenic microorganisms. The antimicrobial activity of each compound was evaluated using the disk‐diffusion assay and the liquid broth assay. All compounds displayed a various spectrum of antibacterial activity. Compounds with the strongest antimicrobial effect were selected for further characterization to determine the minimal inhibitory concentration using serial dilution and absorbance reading. A subset of compounds with antimicrobial effects against plant pathogens were further tested for cytotoxicity and the ability to prevent fruit and vegetable bacterial infections. Future work will focus on using a cell‐culture‐based assay to test the remaining compounds for animal cell cytotoxicity.Support or Funding InformationThis research was done under the support of the U.S. Education Department Title III Part F HSI Grant # P031C160155, the NSF IUSE (Improving Undergraduate STEM Education) Award #1611843, and the New Jersey City University Separately Budgeted Research Fund.
Preeclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex Specific Manners
Authors: Abuiessa Salwa Aburageh , Wedn Abdalla M. , El-Gowilly Sahar M. , Helmy Mai M. , El-Mas Mahmoud M. 
Published: April 2020

Preeclampsia (PE)‐induced fetal programming predisposes offspring to health hazards in adult life. Here, we tested the hypothesis that preeclamptic fetal programming elicits sexually dimorphic inflammatory and cardiovascular complications to endotoxemia in adult rat offspring. Preeclampsia was induced by oral administration of of L‐NAME (50 mg/kg/day for 7 consecutive days) starting from day 14 of conception. Cardiovascular studies were performed in conscious adult male and female offspring pre‐instrumented with femoral indwelling catheters. Compared with non‐PE male counterparts, i.v. administration of lipopolysaccharide (LPS, 5 mg/kg) to PE male offspring caused significantly greater (i) falls in blood pressure, (ii) rises in heart rate and left ventricular contractility (dP/dtmax), and (iii) decreases in time‐ and frequency‐domain indices of heart rate variability. By contrast, the hypotensive and tachycardic actions of LPS in female offspring were independent of the preeclamptic state and no clear changes in heart rate variability or left ventricular function were noted. Measurement of arterial baroreflex activity by the vasoactive method revealed no sex specificity in baroreflex dysfunction induced by LPS. Immunohistochemical studies showed increased protein expression of toll‐like receptor 4 in the heart as well as in brainstem neuronal pools of the nucleus of the solitary tract and rostralventrolateral medulla in endotoxic PE male, but not female, offspring. Enhanced myocardial, but not neuronal, expression of monocyte chemoattractant protein‐1 was also demonstrated in LPS‐treated male offspring. Together, preeclamptic fetal programming aggravates endotoxic manifestations of hypotension and autonomic dysfunction in male offspring via exacerbating myocardial and neuromedullary inflammatory pathways.Support or Funding InformationSupported by the Science and Technology Development Fund, Egypt (STDF Grants No. 14895)
Molecular Characterization of the HIRA Histone Chaperone Complex from Chaetomium thermophilum
Authors: Szurgot Mary , Marmorstein Ronen 
Published: April 2020

The HIRA histone chaperone complex is an essential epigenetic regulator which deposits the histone variant H3.3 onto DNA to condense it into chromatin and to regulate the epigenetic landscape of the cell. Because the HIRA complex and H3.3 deposition is associated with areas of active transcription in the genome, HIRA dysregulation is associated with disordered development, aging, and maintenance of terminally differentiated cell types. The goal of our studies is to understand the molecular basis of H3.3‐specific histone deposition by the HIRA complex. Toward this goal, we recombinantly express orthologs of the four HIRA complex components‐ HIRA, UBN1, CABIN1, and ASF1a‐ from the thermophilic fungus Chaetomium thermophilum for biochemical and structural characterization. We show efficient recombinant expression of each subunit, determine complex stoichiometry using analytical ultracentrifugation, and begin structural analysis using a combination of X‐ray crystallography and cryo‐electron microscopy of the subunits alone, in complex, and with histones.Support or Funding InformationStructural Biology and Molecular Biophysics Training Program, NIH 5‐T32‐GM‐008275‐29; Epigenetics of Aging and Age‐Associated Diseases P01, NIH 5P01AG031862‐12
The Effect of Glutathione on Itraconazole‐Associated Hepatocyte Toxicity in an In Vitro Canine Model
Authors: Kirk Natalie M. , Vieson Miranda D. , Selting Kimberly A. , Reinhart Jennifer M. 
Published: April 2020

BackgroundItraconazole (ITZ) is used to treat many fungal infections in dogs. However, therapy is associated with dose‐dependent increases in liver enzymes in up to 42% of dogs. Glutathione (GSH) precursors are commonly used to treat ITZ‐associated hepatotoxicity, although no studies have investigated the efficacy of this practice.ObjectiveTo identify the effect of GSH on cell survival in an in vitro model of ITZ‐associated hepatotoxicity using canine primary hepatocytes.MethodsUsing a sandwich culture technique, pooled canine primary hepatocytes were incubated for 24 hours with 10‐fold dilutions of GSH (0 to 500 μM). Following GSH pre‐incubation, the cells were exposed to 5‐fold dilutions of ITZ (0 to 50 μM). Cell viability was determined using the neutral red assay after 4 and 24 hours of ITZ exposure (n=3). The effect of ITZ concentration, time, and GSH concentration on cytotoxicity was assessed using multivariate linear regression. Hepatocyte phenotype was assessed by measurement of albumin production using an enzyme‐linked immunosorbent assay (ELISA) kit for canine albumin and morphological assessment via phase contrast microscopy.ResultsCanine hepatocyte cytotoxicity significantly increased with ITZ concentration (p<0.001) and time (p=0.004). Whereas, hepatocyte cytotoxicity significantly decreased with GSH treatment (p<0.001). Maintenance of hepatocyte phenotype was confirmed by continued production of albumin and maintenance of cell morphology over time.ConclusionsThe in vitro model demonstrates dose‐ and time‐dependent ITZ cytotoxicity. Pre‐treating with GSH provides a protective effect against cell death in this model. These results suggest that GSH precursors may have a role in the management or prevention ITZ‐associated hepatotoxicity in dogs. Clinical trials are needed to evaluate their utility for this adverse drug reaction.