Medicine and Health Sciences Commons^™

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased …

Hydroxamic Acid-Based Histone Deacetylase (Hdac) Inhibitors Can Mediate Neuroprotection Independent Of Hdac Inhibition, Sama Sleiman, Yan-Ling Zhang, Jennifer Gale, Manuela Basso, Giovanni Coppola, John T. Pinto, Rajiv Ratan

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer

Lander College of Arts and Sciences Publications and Research

Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcusspecies. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under …

Protein Binding Drug-Drug Interaction Between Warfarin And Tizoxanide In Human Plasma, Eduard Mullokandov, Jennifer Ahn, Andrew Szalkiewicz, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

The goal of the in vitro research was to evaluate the potential for inhibition of warfarin protein binding by tizoxanide. Warfarin was of particular interest for the present investigation because it has been shown to be highly bound to plasma proteins and is a narrow therapeutic index drug. Tizoxanide is an active metabolite of an anti-infective prodrug nitazoxanide and also highly protein-bound medication. Both drugs are expected to be co-administered clinically. Protein binding of warfarin was investigated using a centrifugal ultrafiltration technique. Co-administration of tizoxanide significantly inhibited protein binding of warfarin for all concentrations tested. Tizoxanide increased free fraction (fu) …

Perspectives On: Cyclic Nucleotide Microdomains And Signaling Specificity, Jeffrey W. Karpen

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The author provides an introduction to a special issue on cyclic nucleotides concerning four areas in cAMP compartmentation.

Effect Of Chronic Angiotensin Ii Infusion On Plasma Tnfalpha And Il 6 Levels In Adiponectin Deficient Mice, Alexis O'Brien, Minnette Smith, Jaya Pamidimukkala

College of Osteopathic Medicine (TUN) Publications and Research

Chronic low grade inflammation plays an integral part in the development of many types of cardiovascular diseases. Adipose tissue is a well known source of many proinflammatory mediators. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti-inflammatory properties. Our research goal is to understand if APN deficiency contributes to a proinflammatory milieu especially when provided with an appropriate stimulus. Angiotensin II (ANGII) is a well known prohypertensive agent. Recently, ANGII has emerged as a growth factor and stimulator of proinflammatory cytokine expression in cardiovascular & renal tissue. The present study …

Involvement Of Sigma-1 Receptors In The Antidepressant-Like Effects Of Dextromethorphan, Linda Nguyen, Matthew J. Robson, Jason R. Healy, Anna L. Scandinaro, Rae Reiko Matsumoto

Faculty Publications & Research of the TUC College of Pharmacy

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (s1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of s1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, …

Cardiac Troponin Assessment Following Atrial Fibrillation Ablation: Implications For Chest Pain Evaluation, Jason C. Rubenstein, Jason T. Jacobson, Jeffrey J. Goldberger, Rod Passman, Alan H. Kadish, Michael H. Kim

Office of the President Publications and Research

Background: The range of elevation of troponin I (tI) that is within expected limits from left atrial radiofrequency ablation for atrial fibrillation (AF) is not well described, though such information may be of clinical value.

Objectives: Identify the expected range of tI values post-atrial fibrillation (AF) ablation.

Methods: 31 patients undergoing AF ablation had a single tI level drawn the day following the procedure. Clinical variables were also collected, such as ablation type and radiofrequency (RF) time.

Results: Paroxysmal AF was present in 23 patients, and 8 had chronic AF. The average RF time was 2627.8 …

The Effect Of Maté On Enzymes Involved In The Recovery From Oxidative Stress, Amina Sadik, Theodore Chang

College of Osteopathic Medicine (TUN) Publications and Research

In comparing the effect of Maté to that of green tea, it has been shown that Maté has higher anti-oxidative properties. We have shown that the extract of Yerba Maté, paraguariensis, leaves does indeed have strong anti-oxidative properties through the evaluation of its scavenging activity and its ability of assist cardiomyocytes in their recovery from induced oxidative stress using both spectroscopy, a colorimetric assay and flow cytometry. In order to elucidate the mechanism behind this action, we quantified the enzymes known to be expressed naturally by cells under oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase. These enzymes …

The Hormones Of The Placenta, Shaya Oratz

The Science Journal of the Lander College of Arts and Sciences

The human pregnancy begins with fertilization and implantation. As the embryo evolves and develops within the uterus of the mother, the placenta is formed. The placenta is a transient organ that develops to meet and accommodate specific needs during pregnancy. Its two major functions are the exchange of nutrients and gases between the mother and fetus and its role as an endocrine unit. Through the production and release of many hormones the placenta works to regulate the many necessary physiological changes in the mother in order to maintain the pregnancy, meet the needs of the developing fetus and prepare the …