bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility of erythrocytes from different sources to xenobiotics‐induced lysis
Authors: crupi rosalia , Morabito Rossana , Remigante Alessia , Gugliandolo Enrico , Britti Domenico , Cuzzocrea Salvatore , Marino Angela 
Published: June 2021

As erythrocytes are continuously exposed to plenty of metabolites and toxicants, the aim of the present work is to show whether erythrocytes from different sources may exhibit different susceptibility to hemolysis induced by two classes of xenobiotics, Cnidaria venoms, acting via pore forming mechanism on cell membrane, and Cd2+, inducing cell damage mainly via lipid peroxidation. To this end, the hemolytic power of crude venom from stinging cells of the anthozoan Aiptasia mutabilis and from the scyphozoan Pelagia noctiluca has been tested, along with Cd2+ (5 to 20 mM), on erythrocytes (0.05% v/v) obtained from either rabbit, or dog, or chicken, or human source. Our results show a more significant susceptibility of rabbit erythrocytes to hemolysis induced by both crude venom and Cd2+ than erythrocytes from other sources. This difference seems to rely neither on the different specimens used to extract crude venom, nor on the different mechanism of toxicants. In this light, the present study may contribute: i) to confirm hemolytic test as a suitable biological assay to verify erythrocytes resistance to toxicants; ii) to show variability in hemolytic response to xenobiotics; iii) to propose rabbit erythrocytes as more sensitive to the lytic action of xenobiotics, adding more knowledge about clinical practice and drug development in these animals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Examining the effects of housing temperature on mitochondrial adaptations to exercise and the browning of white adipose tissue
Authors: McKie Greg Lawrence , Medak Kyle D. , Knuth Carly M. , Townsend Logan K. , Shamshoum Hesham , Peppler Willem T. , Wright David C. 
Published: June 2021

The thermoneutral zone for small rodents is ~29–31°C and with decreases in ambient temperature below this there are consequent increases in metabolism to promote thermogenesis. Despite this, many studies report housing mice at room temperature for the convenience of the researchers studying them. As such, the conflicting reports between human and rodent models of exercise‐induced mitochondrial biogenesis in adipose tissue and the browning of white adipose tissue may be explained by the often‐overlooked variable, housing temperature. Male 8‐week‐old C57BL/6 mice were housed in cages with (VWR) or without (SED) running wheels (n = 12/group/condition) for 5–6 weeks at room temperature (RT; 22°C) or at thermoneutrality (TN; ~29°C). Mice housed at TN ran a greater distance. VWR protected against weight gain independent of housing temperature however food intake was greater in both VWR and SED mice housed at RT compared to TN. Inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) mass were reduced following VWR independent of housing temperature and there were main effects of both exercise and temperature to reduce brown adipose tissue (BAT) mass. There was no effect of housing temperature on circulating glucose or glycerol concentrations however NEFA, insulin, and the HOMA‐IR were increased at TN. In eWAT there was a main effect of exercise to increase cytochrome c oxidoreductase core I subunit (CORE1), cytochrome c oxidase, and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) protein content with a main effect of housing temperature for PGC‐1α as well. There was a strong trend for an exercise‐induced increase in pyruvate dehydrogenase (PDH). In iWAT, there was a main effect of exercise and temperature on mitochondrial proteins with VWR leading to the expected increases in PDH, CORE1, COX IV, and PGC‐1α, but reduced markers of mitochondrial content at TN. Most notably protein content of the thermogenic uncoupling protein‐1 (UCP‐1) was undetectable in iWAT at TN. Qualitative histological analysis revealed patches of multilocular adipocytes in iWAT with VWR at RT but not at TN. Together our findings provide novel evidence that while housing mice at TN reduces markers of mitochondrial content in adipose tissue under sedentary conditions, the ability of exercise to increase mitochondrial protein content remains largely intact.Support or Funding InformationOntario Graduate Scholarship Canada Research Chairs ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Muscle contractile activity‐mediated regulation of antioxidant enzymes in oxidative muscle requires p62/SQSTM1 phosphorylation‐induced Nrf2 activation
Authors: Yamada Mami , Iwata Masahiro , Warabi Eiji , Oishi Hisashi , Lira Vitor A , Okutsu Mitsuharu 
Published: June 2021

Enhanced muscle contractile activity, as observed with regular exercise, prevents oxidative stress‐induced muscle wasting, at least partially by improving the antioxidant defense system. p62/sequestosome1 (p62/SQSTM1) competitively binds to the kelch‐like ECH‐associated protein 1, activating nuclear factor erythroid 2‐related factor 2 (Nrf2), which stimulates transcription of genes containing antioxidant/electrophile responsive elements. However, it remains to be determined if this process is activated by regular exercise in skeletal muscle. Here we demonstrate that increased muscle contractile activity enhances antioxidant enzyme expression, Nrf2 translocation into nuclei, and Nrf2 DNA‐binding activity in mouse skeletal muscle. Basal skeletal muscle expression of the Nrf2 target antioxidant gene NAD(P)H‐quinone oxidoreductase 1 (NQO1) is markedly reduced in muscle‐specific Nrf2 knockout (Nrf2 mKO) mice and muscle‐specific p62 knockout (p62 mKO) mice when compared to wild type littermates (WT). Using voluntary running, we demonstrate that regular endurance exercise increases levels of total p62 and Ser 351 phosphorylation of p62, an event that enhances p62 affinity to Keap1, in the oxidative soleus muscle. Regular exercise fails to increase the expression of the antioxidant proteins CuZnSOD (i.e., SOD1) and EcSOD (i.e., SOD3) in the soleus of Nrf2 mKO and p62 mKO. However, the exercise‐mediated elevation of these proteins is preserved in glycolytic skeletal muscle of Nrf2 mKO and p62 mKO mice. Collectively, these findings indicate that p62 and Nrf2 cooperatively regulate the exercise‐mediated increase of antioxidant enzyme expression in oxidative muscle, and that an alternate molecular regulation of these genes predominates in glycolytic muscle fibers in response to regular exercise.Support or Funding InformationThis study was supported by Grant‐in‐Aid for Research Activity start‐up (25882036), Grant‐in‐Aid for Scientific Research (B) (15H03080), Grant‐in‐Aid for Scientific Research (B)(18H03153), Suzuken Memorial Foundation, Toyoaki Scholarship Foundation, The Nakatomi Foundation, and The Uehara Memorial Foundation to Mitsuharu Okutsu.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of OJT007 and OJT008 as Inhibitors of Methionine Aminopeptidases from Mycobacterium tuberculosis
Authors: Kaur Manvir , Onyenaka Collins , Voufo Marie Toukam , Nigro Maria Rincon , Liang Dong , Olaleye Omonike Arike 
Published: June 2021

Despite recent advances in the diagnosis of Tuberculosis (TB), the therapeutic management of this ancient disease is still challenging. Mycobacterium tuberculosis, the causative infectious agent of TB, is the number one cause of death from infectious diseases in the world. According to World Health Organization TB report, globally, 558, 000 people developed multi‐drug resistance TB that was resistant to the most efficacious first‐line drug, rifampicin. The emergence of multi‐drug and extensively drug resistance strains of M. tuberculosis has made the requirement for the development of novel anti‐TB agents imperative. Our research focuses on targeting Methionine Aminopeptidase (MetAP) an essential protein for growth of M. tuberculosis. MetAP is a dinuclear metalloprotease that catalyzes the process of removal of N‐terminal methionine during protein synthesis. N‐terminal methionine excision from peptides and proteins, is a universally conserved process required for stability, localization, biologic maturation and post‐translational modifications of some proteins. This essential role of MetAPs makes this enzyme an attractive target for the development of new therapeutic agents for treatment of TB. Our hypothesis is that, the development of potent and selective mycobacterial MetAP inhibitors may serve as therapeutic agents against infections caused by M. tuberculosis. Here, we report the characterization and pre‐clinical development of two novel structurally diverse small molecules (OJT007 and OJT008), as inhibitors of M. tuberculosis MetAP with potent activity against M. tuberculosis in the low micromolar range in vitro. These results suggest that OJT007 and OJT008 are potential lead compounds for the development of novel small molecules for the therapeutic management of TB. This target‐based approach has demonstrated the utility of MetAPs as promising antimycobacterial targets. Furthermore, we have developed optimal co‐solvent formulations for both OJT007 and OJT008. Preliminary in vivo pharmacokinetic studies for both compounds are in progress. The discovery of new lead compounds to the diminishing anti‐TB pipeline could have potential impact in accelerating the development of new drug candidates for treatment of drug‐sensitive and drug‐resistant TB. In addition, OJT007 and OJT008 may serve as novel chemical probes for understanding the essential role of N‐terminal methionine excision in TB biology.Support or Funding InformationThis research was supported in part, by research infrastructure support from RCMI grant number 2G12MD007605‐22A1 from the NIMHD/NIH.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deficits in Motor Function After Repeated Exertional Heat Stroke Exposure in Female Mice
Authors: Alzahrani Jamal Mohammed , Murray Kevin O , Sheikh Laila , Garcia Christian K , Robinson Gerard P , Laitano Orlando , Clanton Thomas L 
Published: June 2021

Exertional Heat Stroke (EHS) is a life‐threatening illness that can result in a number of negative health outcomes. Once exposed to EHS, patients are considered to be at greater risk of subsequent EHS. In this study we hypothesized that a single EHS exposure would result in greater susceptibility to a second EHS, and that the consequences of EHS on skeletal muscle/motor function would be more profound. Twelve female mice were exposed to an initial EHS, allowed to rest for 2 weeks and then exposed to a second EHS and followed for 1 week. All mice reached symptom limitation (loss of consciousness) at lower maximum core temperatures (Tc, max) in their second EHS. Mice also had lower durations of unconsciousness after the second EHS. We evaluated motor function, before and after the EHS using behavior assessments including trunk curl, horizontal rotation response, catalepsy and a ‘weight test’ protocol. Mice showed a significant decrease in the strength (P = 0.0182) after the second EHS, as measured by the weight test protocol, an impaired rotation response (P = 0.0061), catalepsy (P = 0.0398) and trunk curl (P = .0001). These measures indicate reductions in strength and/or motor coordination. In conclusion, we identified that exposure to EHS increases the susceptibility to a second EHS with worsening outcomes in motor function after the second EHS. These data suggest that following a single exposure to EHS there is a prolonged period of increased vulnerability to EHS and greater potential risk of deficits in organ function.Support or Funding InformationSupported by the BK and Betty Stevens Endowment and a Fellowship from King Saud University, Saudi Arabia.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Evaluation of Alpha‐glucosidase Inhibition by Alcoholic Extract of Garcinia Kola
Authors: Obih Patience O , Obih John‐Clifford A , Nwogu Ivy 
Published: June 2021

Diabetes mellitus is a serious chronic disorder and the 7th leading cause of death in the United States of America. It is a metabolic disorder where the body cannot properly metabolize food for energy. It is a chronic condition that is dramatically increasing every year. Recently, more individuals with diabetes are interested in alternative strategies for treating diabetes such as herbal remedies. The objective of this study was to investigate the alpha‐glucosidase inhibitory potential of alcoholic extracts of Garcinia Kola (Bitter Kola) in regulating post‐prandial glucose levels in diabetes. Garcinia Kola, known in Africa as “Wonder plant” was selected for this study because of its numerous use cited in literqture. The in vitro assay was carried out in a 96‐well microplate. The reaction mixture consisted of 2.5 μL of various dilutions of Garcinia extract, 122.5μl of 0.2M phosphate buffer and 62.5 μL of 5mM para‐nitrophenyl‐α‐D‐glucopyranoside. The mixture was pre‐incubated at 37 °C for 5 min followed by the addition of 62.5 μL of α‐glucosidase solution. The mixture was then incubated for an additional 10 minutes and analyzed with a ThermoScientific® Multiskan Spectrophometer at an absorbance of 400nm. Acarbose was used as a positive control of α‐glucosidase inhibitor. From our observation, Garcinia Kola produced inhibition of alpha‐glucosidase, an indication that it may be useful in reducing hyperglycemia.Support or Funding InformationCenter of Excellence/BUILD, Xavier University of LouisianaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Antidiabetic Activity of Root Tubers of Cyanotis tuberosa in Streptozotocin Induced Diabetic Rats
Authors: apparao chippada , Vedasree N , Peddanna Kotha , Rajasekhar Allagadda , Badri Kameswara Rao 
Published: June 2021

Diabetes mellitus arising due to insufficient insulin production or its action or both is characterized by hyperglycemia. According to WHO it ranks as the third leading cause of death. Presently available antidiabetic drugs have one or more side effects. There is a need for new antidiabetic agents that will have therapeutic effect with fewer side effects. Cyanotis tuberosa is traditionally used as ethno medicine for curing several ailments in India. The objective of this study was to evaluate the antihyperglycemic activity of root tubers of Cyanosis tuberosa (Commelinaceae) in STZ induced diabetic rats. Different doses of aqueous suspension and different solvent extracts (made by soxhlation) were given to the Streptozotocin induced diabetic rats orally by using oral gavage. After treatment aqueous suspension at the dose of 250 mg/kg b.w has markedly (69%) decreased the fasting blood glucose levels after 6 hours of treatment. Whereas among the solvents extracts hexane extract at the dose of 750mg/kg b.w has produced highest (87%) anti hyperglycemic activity than the other solvent extracts and it is higher than that of the standard drug glibenclamide (20 mg/kg b.w). No hypoglycemic effects were observed in the diabetic rats after the treatment. And Cyanosis tuberosa improves the oral glucose tolerance of diabetic rats when given the hexane extract at the dose of 750mg/kg b.w. Phytochemical analysis of the hexane extract revealed the presence of bioactive secondary metabolites such as flavonoids, tannins, saponins, terpenoids, phenolics, and triterpenes which are responsible for antihyperglycemic activity. In conclusion our findings suggest that the hexane extract of Cyanotis tuberosa can decrease the hyperglycemia in diabetic rats most efficiently without any side effects.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of apelinergic system during the development of the cardiovascular system in the offspring of rat dams with depressive‐like behaviour during pregnancy
Authors: Cudnoch‐Jedrzejewska Agnieszka , Czarzasta Katarzyna , Wojciechowska Małgorzata , Segiet Agnieszka , Makowska‐Zubrycka Monika , Kasarełło Kaja , Tyszkowska Karolina , Matusik Katarzyna , Sajdel‐Sułkowska Elżbieta 
Published: June 2021

IntroductionDepression during pregnancy and lactation is a significant clinical problem that affects 7% to 19% of women. Often the depression develops early during the first trimester of pregnancy, during the fetal cardiovascular system development and is associated with increased levels of circulating cortisol that passes through the blood‐placenta barrier. ln turn, the increased cortisol inhibits the apelin synthesis and the apelinergic system activity that is essential for cardiogenesis and angiogenesis during the embryonic and fetal development.PurposeThe main aim of the project is to investigate the effect of apelinergic system on the development of the cardiovascular system in the offspring of female Sprague Dawley rats (SD) with depressive‐like behaviour.MethodsThe research was carried out on 14 rat dams and their offspring of both sexes. Half of the dams underwent chronic immobilization stress to induce depression, the other dams were not stressed. The development of depression in dams was confirmed by a self‐care test and urinary corticosterone concentration. P28 weaned offspring underwent ECHO examination. Following the euthanasia. their hearts were removed for morphological, biochemical, and Real‐Time PCR analysis. Consent was obtained from The Local Animal Research Ethics Committee (031/2016).ResultsHeart morphology was normal and the left and right ventricle function were comparable in the offspring of both control and stressed dams. However, the offspring of stressed dams had a significantly higher left ventricular weight and increased heart rate, while the aortic diameter was lower in these rats compared to the offspring of control dams. Expression of BNP mRNA was significantly higher in the offspring of stressed compared to the offspring of control dams. Glucocorticoid receptor mRNA expression was significantly higher in the offspring of stressed compared to the offspring of control dams. On the other hand the apelin mRNA expression was significantly lower in the offspring of stressed than control dams, whereas the APJ mRNA expression was significantly higher in the offspring of stressed dams.ConclusionOur results indicate that maternal depression during pregnancy and lactation is associated with developmental cardiovascular abnormalities and lower apelinergic system activity. These observations support an important role of apelinergic system in the cardiovascular remodeling of the developing heart in response to maternal depression.Support or Funding InformationThis research was supported by the Medical University of Warsaw, Young Researcher's Grant (1MA/PM2/18).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effects of Cardiolipin on Vascular Smooth Muscle Cell Dedifferentiation and Migration
Authors: Galambo Deema , Bergdahl Andreas 
Published: June 2021

PURPOSEThe initial phases of atherosclerosis involve the transition of smooth muscle cells (SMCs) to a synthetic, dedifferentiated phenotype, which is associated with alterations in receptor, ion channel and contractile filament composition. The late, irreversible atherosclerosis stages are characterized by SMC migration and subsequent formation of a ‘neointima.’ This leads to blood flow obstruction which, when destined to the cardiomyocytes, induces hypoxic conditions and myocardial infarction. Apoptotic cardiomyocytes release a phospholipid called cardiolipin (CL) into the systemic circulation. Previously, we have shown that physiological concentrations of CL inhibit endothelial cell migration. The objective of this project was to investigate the impact of CL on SMCs, specifically addressing cellular dedifferentiation and migration.METHODSFor this study, we used adult, male C57Bl/6 mice. Aortas from these mice were extracted and incubated in Dulbecco's modification of Eagle medium containing physiological CL concentrations (1 μM and 10 μM) at 37°C for 48 hours. We subsequently quantified contractile proteins (such as smooth muscle α‐actin and calponin) using immunoblotting to determine whether CL affects SMC dedifferentiation. These concentrations were also used to investigate the migration of SMCs using a migration assay. For this, we mimicked wounds by scraping off the cell culture plates' diameters to create cell‐free gaps. The plates were then incubated at 37°C for six days, during which the width of the gaps was measured every 48 hours under a light microscope.RESULTSThe immunoblotting results demonstrated a significant drop in calponin in a dose‐dependent manner with increasing CL concentrations, while the other de/differentiation markers remained unchanged. The migration assay revealed that the gap width was significantly narrower in control plates compared to CL‐treated plates.CONCLUSIONSOur results suggest that the effect of physiological concentrations of CL on SMCs is calponin‐specific and does not initiate dedifferentiation within 48 hours. The significantly wider gaps observed in the CL‐treated plates compared to the control plates indicate the potent effect CL has on inhibiting SMC migration. Since SMC migration is considered the key step in the atherogenic progression, our migration assay data suggest that, in a physiological context, CL has the potential to arrest the progression of the disease into its irreversible stages. Thus, we hypothesize the potential involvement of CL in developing anti‐atherosclerosis therapeutics.Support or Funding InformationCanadian Institute of Health Research (CIHR)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.