bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the oncolytic ability of Theiler's murine encephalomyelitis virus in glioblastoma cell lines GL26 and GL261
Authors: Grey Devon , Freundt Eric C. 
Published: June 2021

Glioblastoma multiforme (GBM) is type of brain cancer for which there are no effective treatments. Oncolytic viruses, such as poliovirus, are currently being tested as potential therapeutics in GBM. We recently found that Theiler's murine encephalomyelitis virus (TMEV), a relative of poliovirus, specifically downregulates expression of four transcription factors, known as OLIG2, POU3F3, SOX2, and SALL2 that are required for proliferation of GBM cells. However, these studies were done in stem‐cell derived oligodendrocyte progenitor cells and it is not known if TMEV can disrupt expression of these genes in GBM cells. In this study, we have infected the glioma cell lines GL26 and GL261 with two strains of TMEV, known as DA and GDVII and evaluated infection efficiency by immunofluorescence microscopy. While glioblastoma cells were susceptible to both strains, DA infected with greater efficiency than the GDVII strain. These differences were not observed in a fibroblast cell line, BHK 21 cells, which were equivalently infected by both strains. Chimeric viruses were used to determine whether strain‐specific differences in infectivity were due to capsid proteins of viral nonstructural proteins. Additionally, we assessed the oncolytic capacity and the ability of TMEV to downregulate OLIG2 in GBM cells. These results suggest that TMEV serves as a model to understand how picornaviruses can limit GBM proliferation.Support or Funding InformationDG was supported by the Office of Undergraduate Research and Inquiry Student Research GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physical Therapy and Regenerative Medicine: Current Knowledge and Future Prospects
Authors: Pounders Vance , McArthur Libby , Rinehart Julian , McQueen Ryan , Raynes Edilberto , Roca‐Menchavez Melinda 
Published: June 2021

Disorders affecting the central nervous system (CNS) leave patients with life‐altering disabilities. Injuries that occur in the brain and spinal cord are difficult to treat due to the lack of neuroregeneration in the CNS. Research demonstrates that regenerative medicine and physical therapy techniques can provide structural and functional improvements; however, there is limited research evaluating the combined approach. Regenerative medicine can mitigate the anatomical and physiological destruction caused by a CNS injury; while, physical therapy techniques can help the body restore normal function. The purpose of the study was to evaluate the efficacy of combination therapy using regenerative medicine and physical therapy and its impact on therapeutic outcomes for patients with CNS disorders. Using PUBMed, Google Scholar, and other databases, a systematic review was conducted and ranked using the Oxford Levels of Evidence. Based on the gathered evidence, we surmised that combination of regenerative medicine and physical therapy approaches could facilitate treatment of CNS injuries and lesions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Telling the Truth About Caner is a Challenge
Authors: Markovic Olivera , Markovic Nenad 
Published: June 2021

Cancer is our neighbor and is a part of our society. It has been here from the beginning of history and is still present hiding the truth about itself and being untouchable in its malevolent version: the unstoppable growth of abnormal cells attacking the body until it succumbs to the aggression.Removing all malignant cells from the body is a challenge because it is the only real cure of the affected person. But, it can be done only if the disease is detected in precancerous phase, cancer in situ, and invasive cancer in clinical stage 1A. All more advanced cancers, notwithstanding the therapy employed, have a much worse prognosis. Medicine is there only to postpone the ultimate fatal outcome.But, this is the same with life itself. It is the blessing to have it, but the challenge to live it. Cancer is the curse of our life. Therefore we have to fight against any carcinogenic and cancer promoter factor in our environments, to search for cancer indicators via surveys among healthy peoples, to put under control the groups at risk, and to conduct regular screening for detection of early signs of cancer as diligently as it has been done in the case of cervical cancer.In this fight, medicine has made many advantages but the cancer is still present. Only a small fraction, the cervical cancer natural history has been altered due to detection of an early suspect for cancer lesions and their removal. The success was achieved in the US where Pap test has helped American health care providers to reduce its mortality rate for 80% and to reverse the curves of cancer prevalence and mortality from increasing pattern to decreasing.This success was achieved in a group of 50 million women at risk, where 10% were found as suspect, subject to further diagnosis, only 1 million was confirmed as carrying on cancer indicators, and 40,000 lesions removed. Still, due to errors in sampling specimens, diagnostic errors or ineffective therapies, 12,000 joined the prevalence and 4,000 died per annum.Worldwide, this concept failed. The global outreach is below 20% of women at risk, and curves of cervical cancer prevalence and mortality are still on rise. What can be done? It was our humble challenge for more than 30 years of research. Finally, a light started to appear in the tunnel of cervical cancer destiny. It is the change of the strategy from the fight against cervical cancer to the fight to reverse the Cervical Cancer Mortality curve in a definite population and for a definite time. The new strategy needs new tools and services. All of this is described in our book, What Every Women Should Know about Cervical cancer, Second Edition (Springer, 2017)Parts were discussed at FASEB meetings in 2016 and 2017. This is a continuation of publishing the results of our research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
How the DAG generation, transient shuttling of effector molecules and assembly of a signalosome at immunological synapse can regulate the early T cell response and L‐selectin shedding?
Authors: Aslam Naveed , Alvi Farah 
Published: June 2021

Tunability of T cell activation profile could be key in orchestrating the optimal immune system response in pathologies like autoimmune, inflammation, allergies and some cancers. During early T cell activation events the fundamental proteolysis process of L‐selectin shedding is critically linked to the precision and specificity of immune response. Considerable evidence links the DAG homeostasis at immunological synapse to L‐selectin shedding and early T cell activation profile through DAG‐PKCα‐DGKζ‐Ras/ERK axis. Evidence also suggest that generation and consumption of this lipid at T cell‐APC contact zone must be exquisitely regulated due to its critical role in T cell polarization and activation. Here, we explore the question that how during the correct activation of antigen‐specific immune response DAG limits its own persistence? Understanding how the DAG homeostasis can be maintained could be significant for establishing a link between TCR triggering and Ras/ERK activation. Here, we report that a net negative feedback loop which is modulated by second messenger itself is responsible for maintaining the homeostasis and hence the precision and specificity of immune response. Here, we show that a local signalosome and functional sub‐signaling loop is formed between the components of DAG signaling which in turn, ensure the precision in degree of proteolysis of surface molecules such as L‐selectins. The coordinated translocation to I.S. in response to antigen recognition and subsequent activation of PKCα and DGKζ regulated the amplitude and duration of persistence of DAG levels. Our results propose that during the normal physiological conditions this sub‐signaling loop between DAG effector molecules is responsible for tightly maintaining the second messenger homeostasis however, under the pathological conditions this loop may become dysfunctionalSupport or Funding InformationPrivate FundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cadmium‐induced Macrophage LDL and Oxidized LDL Internalization
Authors: Kumar Wasan Mani , Ribeiro Marta , Balla Andre 
Published: June 2021

Environmental cadmium exposure has been established as a promotor of vascular inflammation and risk factor for atherosclerosis. Inflammation causes histone release, which was shown to increase macrophage low‐density lipoprotein (LDL) phagocytosis, which initiates foam cell formation, a crucial step in atherosclerosis. The link between histones and macrophages suggests cadmium may increase atherogenesis by upregulating scavenger receptors, which function to bind LDL and Oxidized LDL (OxLDL).RAW 264.7 (murine) macrophages were incubated in a solution of DMEM (Dulbecco's Modified Eagle Medium) and treated with 2 μg LDL, 2 μg histones, and 10 nM, 50 nM, and 200 nM CdCl2 concentrations with varying incubation times (24 hr, 48 hr, and 72 hr). Cells were stained using Oil Red O (lipid sensitive dye) and imaged using a microplate reader at 500 nm. LDL was oxidized by incubation in 10 μM CuSO4 and centrifugal filtration in a PD‐10 spin column. OxLDL was diluted to 2 μg/ml and applied to macrophage cells with the aforementioned conditions, excluding histones. Oil Red O staining and absorbance measurement were performed with similar time constraintsIn vivo studies for measurement of serum LOX‐1, CD‐36 and SR‐A I/II were also performed. LOX‐1, CD‐36, and SR‐A I/II are the main macrophage and endothelial receptors for oxidized LDL. ICR male Mice were exposed to cadmium through drinking water for 8 weeks. Mice were sacrificed, and serum was extracted for assessment of scavenger receptor expression by ELISA assay.Oil Red O staining of RAW 264.7 cells incubated with 2 μg LDL, 2 μg histones and 10 nM, 50 nM, and 200 nM CdCl2 concentrations showed significant dose‐dependent and time‐dependent (24, 48, and 72 hr.) increases in lipid absorbance. Those at the highest CdCl2 concentrations showed the largest increase in LDL uptake, further augmented by histones. Similar results were found in macrophage cells incubated with 2 μg OxLDL. The serum ELISA provided inconclusive results to LOX‐1 serum concentrations.Our data indicates cadmium modulates macrophage function to promote the uptake of LDL, histone‐LDL and OxLDL. We are currently studying the in vitro expression of major scavenger receptors, including LOX‐1, CD‐36 and SR‐A I/II that may provide insight into the mechanism of action for cadmium adverse effects on macrophages.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dose‐specific morphological changes in the Sertoli cell of the adult male Japanese quails testes exposed to di(n‐butyl)phthalate DBP prepubertally
Authors: Bello Umar M. , Aire Tom A. , Imam Jibrin , Abdulazeez Jimoh , Igbokwe Casmir O. 
Published: June 2021

Di(n‐butyl) phthalates (DBP) are endocrine‐disrupting chemicals (EDCs) implicated in a number of reproductive disorders in humans and rodents. Previously, we have shown that DBP effects is anti‐androgenic and causing alterations in seminiferous tubular histology and impairment of Leydig cell steroidogenesis in the avian model. However, the ultrastructural changes on the Sertoli cell remain unclear. The present study was designed to assess, morphologically, the dose‐dependent toxic effect of pre‐pubertal exposure of the plasticizer‐DBP, on the histology and ultrastructure of the Sertoli cell. DBP was administered to 10‐week old male quail birds by oral gavage, with a control group given corn oil vehicle(1mL/kg) only, while the other five experimental groups were fed (1, 10, 50, 200– and 400mg/kgbwt/d DBP(dissolved in corn oil) , for a period of 30days. Testes were fixed in Bouin's liquid or in a mixture of 2.5% glutaraldehyde and 2% formaldehyde for analysis under light and electron microscopes(TEM), respectively. Histologically, the basal Sertoli cell cytoplasm in high DBP dosage levels (200mg and 400mg/kgbwt/d), increasingly displayed aggregations of lipid droplets, but only a few in the apical Sertoli cell cytoplasm. In addition, there was marked vacuolations in the lining germinal epithelium. Ultrastructurally, there were notable, dose‐dependent changes seen in the Sertoli cell in DBP‐treated birds, with low dosage groups displaying no obvious structural changes, while the DBP high‐dose resulted in a remarkable accumulation of numerous, scattered or usually, closely packed lipid droplets, found predominantly in the basal part of the Sertoli cell cytoplasm. In addition, there were several mis‐shaped or swollen mitochondria with electron lucent areas, indicative of early cellular degeneration. These degenerating mitochondria were characterized by swelling and deformation of the tubular cristae, resulting in a “moth‐eaten” appearance. These findings showed that high dose of DBP (200 and 400mg/kgbwt/d) administered daily for 30days significantly resulted in degenerative characteristics, such as the increase in lipid droplets, intra‐epithelial vacuolations and mitochondrial damage in the Sertoli cell. Thus, this study has provided a clear evidence that alterations in Sertoli cell morphology and function were involved in spermatogenic failure induced by DBP, in this specie.Support or Funding InformationThe research was supported by Ahmadu Bello University Board of Research and grants from the South African Veterinary/Novartis Wildlife Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Repurposing neuroleptic drug for brain tumor therapy
Authors: Kaushik Itishree , Srivastava Sanjay 
Published: June 2021

Brain tumor is considered as one of the most aggressive and incurable form of cancer. Majority of the brain tumors have a median survival rate of only 12%. Even though advanced treatments such as surgical removal, chemotherapy and radiotherapy are available, brain tumor persists to be lethal. Temozolomide (TMZ) is the main therapy for brain tumor but resistance to TMZ is the major cause of treatment failure. This resistance in tumor cells has frequently been linked to the expression of O6‐methylguanine‐DNA methyltransferase (MGMT). Pimozide (PMZ) is a neuroleptic drug used for the treatment of schizophrenia and chronic psychosis. In our study, we observed that pimozide significantly reduced the viability of U87MG, U251MG, DAOY and GBM28 cell lines with an IC50 ranging from 11μM to 20μM after 24 h of treatment. Pimozide induced apoptosis in these cell lines as evaluated by FITC/Annexin assay and further validated by the cleavage of caspase 3 as well as PARP. Western blot analysis resulted in the concentration dependent decrease in the expression of STAT3 signaling mainly targeting the anti‐apoptotic markers BCl‐XL, BCl‐2 and Survivin etc in U87MG, U251MG, DAOY and GBM28 brain cancer cell lines. PMZ alone suppressed the growth of U87MG cells with an IC50 of 10μM, after 96 hours of treatment. On the other hand, treatment of U87MG cells with 750 μM of TMZ in combination with 10μM PMZ for 96 hours increased the killing of U87MG cells by 50% as compared to 10% when treated with TMZ. In addition, PMZ treatment reduced the survival of TMZ resistant U251R cells with an IC50 ranging from 15–20 μM after 24 h of treatment. Our results further demonstrated that oral administration of PMZ (25mg/kg) significantly inhibits the growth of brain tumors in an intracranial tumor model without any apparent signs of toxicity. It is important to note that PMZ is an FDA approved drug with no considerable toxicity. Overall, this study depicts that PMZ is a potential candidate to target brain tumors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Case‐Based Discussion to Review Infectious Disease Therapeutics in a Graduate Physician Assistant Studies Program
Authors: Guillory Ashley Nicole 
Published: June 2021

Infectious disease therapeutics have historically been a difficult topic for the physician assistant students at University of Texas Medical Branch. Average test scores on the exam covering these topics are typically 5–10 points below the class average of other exams. In order to improve students' test scores and understanding of this material, a case‐based review session was added at the end of the infectious disease module.The review session began with a short lecture (~30 minutes) reviewing high yield concepts as preparatory material. The lecture slides were made available to students 2 days prior to the review session. Students were divided into small groups and assigned 1–2 short cases covering the different classes of infectious disease therapeutics. Each case included questions related to choosing the most appropriate treatment, the pharmacological characteristics of the treatment, and alternatives due to patient characteristics such as renal failure, pregnancy, and hepatic insufficiency. Students worked through cases in their small groups then reconvened to present their case and answers to the entire class. A post‐session survey was given to determine both student satisfaction with the session as well as the impact of the session on their knowledge and understanding of the material. Effectiveness was assessed by the test scores on the exam for the infectious disease module.Prior to the review session, 82% of survey respondents indicated that they lacked confidence in their knowledge of infectious disease topics. Following the review session, only 23% of respondents indicated that they still lacked confidence in their knowledge of these topics. 97% of survey respondents indicated that the review session was beneficial with the majority of respondents indicating that it was very beneficial. The survey also included a free response question for students to offer feedback on the session and ways to improve the session. Themes that were discovered in these answers included: 1) students felt that they should have studied more before attending the session, 2) have the cases instructor led rather than the majority of the discussion happen in the individual groups, and 3) incorporate the case studies into the lecture portion. Overall, the response to the review session was largely positive and the feedback will be useful for improving the review session next year. This format will be useful in developing review sessions for other pharmacology topics that the students struggle with.Support or Funding InformationThis study was not supported by a grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
“Memory clinics:” A complement to teaching and learning in pharmacology
Authors: Silva Ricardo Alfonso Pena , Larrarte Maria Alejandra 
Published: June 2021

Pharmacology is considered one of the most difficult subjects by medical students. One of the reasons that explains the difficulty is the need to learn multiple names of medications that are not familiar to the medical student. To support the learning of pharmacology, we have developed "memory clinics" to offer a metacognitive space that allows the student to reflect on their study methods and fears when learning pharmacology."Memory clinics" are a voluntary activity in which medical pharmacology students can participate. The activity takes place in several stages during a one‐hour block. 1) Two short study sessions (individually, individually or in groups) to memorize biomedical information related to pharmacology. 2) retention of information is evaluated in a short activity in which the students solve a crossword puzzle. At the beginning, in‐between the sub‐stages and at the end of the activity the students answer some open questions in which they reflect about confidence in their mastery of the concepts and time devoted to study and answer questions. At the end of the activity, the correct answers to the questions are given and each student evaluates his/her own performance.The piloting of innovation shows that students are very pleased with the activity and recognize the importance of having a space to reflect on their learning processes. At the beginning, only three "memory clinics" were planned, but students have requested that more activities of this type be included, because they feel that innovation has favored their learning process.Support or Funding InformationCollege of Medicine, Universidad de los AndesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Clinical Pharmacology Learning Tools for the Tech Savvy in a Physician Assistant (MPA) Program
Authors: Ram Arun M , Rajasekaran Senthilkumar 
Published: June 2021

Students of our MPA program are expected to master a vast amount of information in a short 28‐ month curriculum leading up to their clinical practice. In addition, students find learning clinical pharmacology difficult as it involves memorizing hundreds if not thousands of medications, their mechanism, interactions, and adverse effects. In order to maximize learning, we delivered a Clinical Pharmacology (CP) course in a flipped classroom model using technology1.CP I and II are two 3‐credit courses taught over 4‐month each with two 2‐hour didactic lectures every week. In its place, we introduced short 15 – 20 minute videos recorded using Explain Everything or Camtasia software and posted them a couple of days prior to in‐class sessions2. In addition, a complete slide‐deck and a study guide with open‐ended questions designed to reinforce the clinically relevant facts and concepts in each class were also posted. Students listened to the recording, used the slide‐deck and study guide to master the concepts. An anonymous survey at the end of the course collected the feedback on this new model of course content delivery and their learning experience3.More than 55 students participated in the survey. An overwhelming 82% of the respondents wanted the course to be delivered based on this model in the future. About 75% agreed that the new model allowed them more time to study other subjects. Another 76% felt the new model helped them feel prepared for the exams. Although we had reduced the student‐faculty contact time by 50%, about 70% of the survey respondents felt the new model provided them adequate faculty exposure and interaction.Unlike reported by some studies that the students prefer only about half of the class sessions to be “flipped” 4; our MPA students wanted us to follow this new model for the entire course. Following our success with this new model, other Course Directors have started introducing flipped classes in their courses.Based on the favorable feedback we received from the students and performance index on their course assessments, we recommend utilizing this model of active learning in your health sciences education programs.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.