bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibacterial Screening Of Ethanolic Pomegranate Peel Extract
Authors: Jackson Destiny , Abu-Niaaj Lubna Fawzi 
Published: April 2020

Pomegranate (Punica granatum L.) is reputed for its nutritional properties. This fruit is rich in antioxidants, vitamins, and minerals. The juice industry produces a high quantity of peel that is thrown away despite of its richness of bioactive compounds. The increased demand for environmentally friendly pharmaceutical agents brought attention to commercializing the use of fruit peel.ObjectivesThis study aims to 1) evaluate the antibacterial activity of ethanolic pomegranate peel extract on six bacteria that cause food spoilage or are associated with human diseases., and to 2) determine the effect of temperature on the antimicrobial activity induced by the pomegranate peel ethanolic extract.Material and MethodsThe growth inhibition by the pomegranate peel extract was evaluated on Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Micrococcus luteus. Fresh pomegranate peel was dried, grinded into fine particles, and stirred in ethanol for 30 minutes either at room temperature or with gentle boiling. Both extract preparations were filtered, wrapped with aluminum foil to avoid photooxidation. The pH measurement was recorded immediately, then daily for at least 30 days. The crude (gummy) material is a concentrated extract which was tested on bacteria at a concentration of 40ug/μl. The antibacterial activity of was determined using agar well diffusion method. The bacterial were cultured into prepared nutrients broth and incubated at 37°C for 24 h and standardized to 0.5 Mc‐Farland Scale (108 cfu/mL) in a prepared normal saline. The cell suspensions were seeded into prepared nutrients agar plates, and wells of 8mm were bored into the agar. The screening was done by placing 100ul in a well of either the extract, or the crude that was prepared at 40ug/μl.ResultsThe ethanolic extract and crude of pomegranate peel showed varying degree of antibacterial activity against the tested bacteria. The inhibition zone range was between 14–28 mm and it was sustained for up to 72hr. The high temperature preparations showed a minimum of 10% more antibacterial activity. The pH measurements showed stability for at least 30 days for all preparations kept in the refrigerator.ConclusionIt appears that the pomegranate peel has the potential for use in food applications as a natural preservative, and also in pharmaceutical applications.Support or Funding InformationNSF‐IPSRG, LSAMP Grant and Land Grant
Changes in Sensory Functions in Response to Living in an Extreme Underwater Saturation Environment
Authors: Ari Csilla , Bharwani Sahil , Rehsi Anand , Moss Sara , Schmer-Galunder Sonja , Fiore Stephen , D’Agostino Dominic Paul 
Published: April 2020

The present challenges of long duration spaceflight and other missions in extreme environments include changes of sensory functions, including vision impairment and changes in taste perception. In order to monitor and improve astronaut health and performance during long duration spaceflight and future spaceflight missions we studied sensory functions in response to living in an extreme environment during the NASA Extreme Environment Mission Operation (NEEMO) 23. The Aquarius Reef Base is located at 20 m (66 ft) with 2.6 atm (air) pressure inside the habitat, while levels of CO2 are elevated similarly to the International Space Station.This study assessed the changes in visual acuity and taste perception in 6 NEEMO 23 subjects (2 males, 4 females) 1 day before the mission, during the mission at half time and 1 day post mission. Visual changes were assessed using the NIH Toolbox protocol, while changes in taste perception were measured using solutions containing concentrations of either salty, sweet and bitter flavors in three different concetrations on the side of the tongue and in full mouth.We observed a trend of decreased salty and bitter taste sensation in the habitat and post mission, compared to baseline, while the sweet taste sensation did not change. When testing the full mouth, the salty taste sensation significantly decreased post mission, compared to baseline at low or medium concentration. Bitter taste sensation significantly decreased at low concentration in habitat and post mission, compared to baseline. At medium concentration the bitter taste sensation significantly decreased post mission, compared to baseline and in‐habitat, while at high concentration it significantly decreased post mission, compared to baseline. There was a signifcant reduction in the Overall Raw and in Overall Uncorrected Vision Scores between baseline and post mission indicating a significant reduction in visual acuity during the 9 days mission that was not restored immediately after the mission.Living in a saturation environment decreases certain sensory modalities that may persist for an unknown length of time after the exposure. Diminished sensitivity to taste can alter nutritional status and chemosensory changes may also relate to space sickness, stress and psychological factors, while changes in vision may impair operational tasks. These data indicate that mitigation strategies need to be developed and tested in space analog environments.Support or Funding InformationKetone Technologies LLC provided partial funding for the study. SIFT provided partial salary for CA.
A Novel Multi‐marker Discovery Approach Identifies New Biomarkers for Parkinson’s Disease in Older People: an EXosomes in PArkiNson Disease (EXPAND) Ancillary Study
Authors: Calvani Riccardo 
Published: April 2020

Dopaminergic nigrostriatal denervation and widespread intracellular α‐synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi‐marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age‐matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO‐CovSel), a multi‐platform regression method developed to handle highly correlated variables organized in multi‐block datasets. The SO‐CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)‐1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP‐1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as valuable biomarkers for PD as well as unveil new targets for interventions.Support or Funding InformationInnovative Medicine Initiative‐Joint Undertaking (IMI‐JU #115621)
The Relation between Immune Cell Mitochondrial Respiration and Brachial Artery Pulse Pressure in Humans
Authors: DeConne Theodore M. , Muñoz Eric R. , Sanjana Faria , Hobson Joshua C. , Martens Christopher R. 
Published: April 2020

Elevated pulse pressure (PP) occurs with advancing age due to stiffening of the elastic arteries and is an important risk factor for cardiovascular disease (CVD), even among normotensive adults. Mitochondrial function declines with aging and may contribute to the increase in PP through a mechanism involving oxidative stress and chronic inflammation; two important hallmarks of arterial aging. Emerging evidence indicates that mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) is negatively associated with risk factors for CVD in heart failure; however, the role of impaired mitochondrial function on cardiovascular function in healthy adults is not known. We hypothesized that mitochondrial function would be negatively associated with brachial PP. Twenty‐two healthy adults free of overt CVD (12 M/10 F; age: 56 ± 21 years; age range: 22–78 years; blood pressure, BP: 123 ± 15/72 ± 10 mmHg; PP: 51 ± 11 mmHg) were included in this analysis. PP was determined from brachial artery BP assessed in triplicate in the non‐dominant arm using an automated BP monitor. PBMCs were isolated by density dependent centrifugation and used to assess mitochondrial function by respirometry using an Agilent Seahorse XFp Analyzer. Primary outcome measures included the oxygen consumption rate (OCR) at baseline (basal respiration; BASERESP) and following three serial injections of oligomycin, FCCP and rotenone/antimycin A into the respirometer to determine maximal respiration (MAXRESP). Spare respiratory capacity (SRC), an indicator of how well the cell can respond to an increased energetic demand, ATP‐linked oxygen consumption (ATPO2), and coupling efficiency, which is how well ATPO2 is matched to BASERESP, were also measured. The associations between mitochondrial function and PP were analyzed using multi‐linear regressions correcting for age. PP was not associated with BASERESP (p=0.89, R2=0.10, β=0.01), coupling efficiency (p=0.20, R2=0.18, β= −8.5), or ATPO2 (p=0.33, R2=0.15, β= −0.10). However, PP was inversely associated with MAXRESP (p=0.05, R2=0.28, β= − 0.03) and SRC (PP; p=0.02, R2=0.33, β=−0.04). These data suggest that the impaired mitochondrial respiration may be an important contributor to CVD risk through increases in pulse pressure. Future studies should explore whether these associations are mediated by increases in oxidative stress and inflammatory cytokines.Support or Funding InformationFunding Sources: P20GM113125, K01AG054731
Novel Insights into the Role of Soluble Epoxide Hydrolase in Adipogenesis
Authors: Alquraishi Mohammed , Puckett Dexter L. , Chahed Samah L. , BAETTAIEB AHMED 
Published: April 2020

Obesity is a growing epidemic that presents a major health problem worldwide. The past decade has seen advances in the identification of specific factors that contribute to this condition. However, despite these strides, there is still much to be learned about the underlying mechanisms. A better understanding of these biochemical mechanisms will enhance our ability to prevent and treat obesity. This study demonstrates that modulation of epoxy fatty acids (EpFA) metabolism in mouse white adipocytes alters cell cycle progression and clonal expansion. In addition, CRISPR/Cas9‐mediated deletion of soluble epoxide hydrolase (sEH), a cytosolic enzyme which hydrolyzes epoxy fatty acids (EpFA) into less active diols, resulted in alterations in adipogenesis. Similar findings were obtained using a selective sEH inhibitor 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU). Importantly, mice with specific deletion of sEH in the adipose tissue were resistant to high fat feeding and exhibited increased energy expenditure. Taken together, the present study demonstrates that modulation of sEH activity in white adipocytes alters adipocyte differentiation and improves glycemic control. Additionally, our findings suggest that sEH is a physiological modulator of adipogenesis and a potential target for the development of novel anti‐obesity therapeutic strategies.Support or Funding InformationThis work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R00DK100736) to A.B.
Influence of Uracil‐Guanine mispair on the Structure of the DNA and the surrounding water
Authors: Zahran Mai , Melo Ivan 
Published: April 2020

The process of repairing damaged bases in DNA molecules plays an important role in the maintaining the information stored in the DNA. How are repair enzymes able to efficiently find the mutated base pair to repair? We hypothesized that two factors may facilitate the recognition. The first is the structural changes in the mutated DNA, the second is the changes in the thermodynamic properties of the water surrounding the DNA. Here we investigate the effects of a Uracil‐Guanine mispair on the structure of the DNA as well as on the static and dynamic properties of the surrounding water. We performed molecular dynamics simulations of the mutated and non mutated DNA molecules, and calculated the structure parameters, and the distribution and dynamics of the water molecules near the DNA structures. We show a distinct structural difference for the Uracil‐Guanine mispair and a different dynamical behaviour of the water molecules which slow down near the mutated base. Both factors seem to enhance the ability of the enzyme to recognize the target mutated base pair.Support or Funding InformationWe thank NYCCT for their support.
Zyflamend Induces Apoptosis in Pancreatic Cancer cells via Modulation of the JNK Pathway
Authors: Puckett Dexter L. , Alquraishi Mohammed , Chahed Samah L. , Donohoe Dallas R. , Whelan Jay , BAETTAIEB AHMED 
Published: April 2020

Current pharmacological therapies and treatments targeting pancreatic neuroendocrine tumors (PNETs) have proven ineffective, far too often. Therefore, there is an urgent need for alternative therapeutic approaches. Zyflamend, a combination of anti‐inflammatory herbal extracts, that has proven to be effective in various in vitro and in vivo cancer platforms, shows promise. However, its effects on pancreatic cancer, in particular, remain largely unexplored. Herein, we demonstrate that Zyflamend treatment decreased cell proliferation in a dose‐dependent manner, concomitant with increased apoptotic cell death and cell cycle arrest at the G2/M phase. At the molecular level, treatment with Zyflamend led to the induction of ER stress, autophagy, and the activation of c‐Jun N‐terminal kinase (JNK) pathway. Notably, pharmacological inhibition of JNK abrogated the pro‐apoptotic effects of Zyflamend. Furthermore, Zyflamend exacerbated the effects of streptozotocin and adriamycin‐induced ER stress, autophagy, and apoptosis. These studies identify Zyflamend as a potential novel approach to treat pancreatic cancer via modulation of the JNK pathway.Support or Funding InformationThis work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R00DK100736) to A.B.
Cannabidiol (CBD) Improves Cognition and Decreases Anxiety in the SAMP8 Mouse Model of Alzheimer’s
Authors: Farr Susan Anne , Goodland Monica N. , Niehoff Michael L. , Young Benjamin J. 
Published: April 2020

The use of cannabidiol (CBD) has grown rapidly over the last few years. CBD has been purported to work on a range of conditions, including anxiety, epilepsy, pain, and psychosis. There has been recent interest in CBD as a treatment for age‐related cognitive disorders due to its anti‐inflammatory properties. Here, we tested the effects of chronic CBD administration on learning and memory in the SAMP8 mouse model of Alzheimer’s disease. SAMP8 mice develop an age‐related impairment in learning and memory which corresponds to an increase in amyloid‐β (Aβ), hyperphosphorylated tau, oxidative stress, impaired efflux of Aβ across the blood‐brain barrier and neuroinflammation. SAMP8 mice starting at 11 months of age were treated with CBD (0, 3 or 30 mg/kg) daily via oral administration for 60 days. A 3 month old SAMP8 group receiving vehicle served as an unimpaired control. After 30 days of treatment, learning and memory (T‐maze and novel object recognition), activity in open field, anxiety in the elevated plus maze, and strength were assessed. Mice which received CBD 30 mg/kg had significant improvement in learning and memory in the T‐maze, taking fewer trials to reach criterion than 12 month old vehicle treated mice. CBD improved object recognition memory of 12 month old SAMP8 mice, which spent significantly more time with the novel object in the 24‐hour retention test than the age‐matched vehicle treated controls. While there was no difference in total distance traveled measured by open field activity, the mice that that received CBD displayed decreased anxiety in the elevated + maze at both 3 and 30 mg/kg/day doses compared to the age‐matched control. The mice that received 3 mg/kg/day had significantly less anxiety than the young control group. CBD had no significant effects on the measures of strength in the aged mice. Our results indicate that CBD improves both spatial and recognition memory and decreases anxiety. CBD is a potential treatment for age‐related dementia.Support or Funding InformationPilot funding from the Edward A. Doisy Department of Biochemistry and Molecular Biology at Saint Louis University
Gas6‐Axl Double Knockout in Mice Decreases Skeletal Muscle mass Despite Elevated Anabolic Intracellular Signaling
Authors: Olsen Zachary E. , Mervis Matthew J. , Matsumura Marc S. , Hirschi-Budge Kelsey M. , Arroyo Juan A. , Reynolds Paul R. , Thomson David 
Published: April 2020

Growth arrest specific‐6 (Gas6) is a signaling factor that has been shown to contribute to growth and survival in various cell types. It functions primarily by activating the receptor tyrosine kinase Axl. Very little is known about the role of Gas6‐Axl in skeletal muscle. Therefore, we studied muscle size and anabolic signaling in Gas6‐Axl double knock‐out mice (dKO). Hindlimb muscle mass was decreased in dKO mice. Skeletal muscle phosphorylation of Akt was not affected by genotype. However, extracellular signal‐related kinase (Erk), ribosomal protein subunit 6 (S6) and p70S6 kinase (S6k) phosphorylation was elevated in dKO muscles. We conclude, therefore, that anabolic signaling through these pathways does not explain the difference in muscle mass between genotypes. We speculate that the elevated anabolic signaling in dKO muscles is perhaps an adaptive compensation for other impaired anabolic processes in these muscles.Support or Funding InformationThis work was supported by a grant from the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU Graduate Research Fellowship.
A novel therapeutic opportunity for the most aggressive sub‐type of pancreatic cancer: Targeting keratin 17 dependency on nuclear export
Authors: Bai Ji Dong (Karen) , Leiton Cindy V. , Pan Chun-Hao , Escobar-Hoyos Luisa , Shroyer Kenneth R. 
Published: April 2020

Introduction and hypothesesThe purpose of this study was to uncover a novel targeted therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). We previously discovered that keratin 17 (K17) is an independent negative prognostic biomarker for PDAC, where high K17 expression is associated with decreased patient survival. In our pre‐clinical mouse model, PDACs that overexpress K17 were four times more likely than controls to result in fatality within 7 weeks, suggesting that K17 drives tumor aggression. We determined that K17 functions as an oncoprotein by translocating into the nucleus of PDAC cells and enhances XPO‐1‐ mediated nuclear export and degradation of tumor suppressor proteins (TSPs).Here, we hypothesized that 1) K17 depends on nuclear export to drive tumor aggression and is highly sensitive to nuclear inhibition, compared to K17‐negative PDACs, and 2) blocking K17 enhanced XPO‐1‐mediated nuclear export causes enhanced apoptosis and cell cycle arrest.Methods and resultsTo test the hypothesis that K17 depends on nuclear export to drive tumor aggression and is more sensitive to nuclear inhibition than K17‐negative PDACs, we performed pre‐clinical studies in mouse models and orthotopically implanted isogenic murine PDAC cells (LSL‐KrasG12D, LSL‐Trp53R172HPdx‐1‐Cre, KPC) that expressed human K17 (KPC‐K17) or not (KPC‐EV) in immunocompetent animals. After animal randomization, mice were treated three times weekly via oral gavage with selinexor, an inhibitor of the nuclear exporter, XPO‐1, that is currently in phase 2 clinical trials. We found that selinexor inhibited the growth of K17‐positive PDACs in mice, compared to K17‐negative PDACs, suggesting that K17sensitizes PDACs to selinexor treatment. To determine if this decreased tumor growth was due to a tumor‐cell nuclear export blockage, we performed in vitro studies and found that KPC‐K17 cells elicited a four‐fold increase in cell death and a two‐fold increase in G1/S cell cycle arrest compared to KPC‐EV cells. In addition, selinexor treatment led to nuclear retention of K17. To test the dependency of KPC‐K17 cells to K17‐mediated nuclear export, we challenged the cells to chemotherapeutic and targeted therapeutic agents that induce nuclear import inhibition (ivermectin), G1/S transition inhibition (palbociclib), and DNA‐damage (oxaliplatin). In contrast to selinexor treatment, there were no differences in cell death or cell cycle arrest between KPC‐K17 and KPC‐EV cells upon treatment with these compounds.ConclusionsOur results suggest that K17‐positive tumors are specifically vulnerable to inhibition of nuclear export. Given that K17 expression is a biomarker that drives tumor aggression in PDACs, our results suggest that treatment with selinexor is a novel therapeutic opportunity for the most aggressive sub‐type of pancreatic cancer.Support or Funding InformationPancreatic Cancer Action Network