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Philadelphia College of Osteopathic Medicine

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Full-Text Articles in Medicine and Health Sciences

Generation And Application Of Inducible Chimeric Rna, Yichen Luo, Liang Du, Zhimeng Yao, Fan Liu, Kai Li, Feifei Li, Jianlin Zhu, Robert P Coppes, Dianzheng Zhang, Yunlong Pan, Shegan Gao, Hao Zhang Jan 2022

Generation And Application Of Inducible Chimeric Rna, Yichen Luo, Liang Du, Zhimeng Yao, Fan Liu, Kai Li, Feifei Li, Jianlin Zhu, Robert P Coppes, Dianzheng Zhang, Yunlong Pan, Shegan Gao, Hao Zhang

PCOM Scholarly Works

Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of …


Meglumine Exerts Protective Effects Against Features Of Metabolic Syndrome And Type Ii Diabetes, Arturo Bravo Nuevo, Alice Marcy, Minzhou Huang, Frank Kappler, Jennifer Mulgrew, Lisa Laury-Kleintop, Melvin Reichman, Annette Tobia, George C Prendergast Jan 2014

Meglumine Exerts Protective Effects Against Features Of Metabolic Syndrome And Type Ii Diabetes, Arturo Bravo Nuevo, Alice Marcy, Minzhou Huang, Frank Kappler, Jennifer Mulgrew, Lisa Laury-Kleintop, Melvin Reichman, Annette Tobia, George C Prendergast

PCOM Scholarly Works

Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, …


Modulation Of Myocardial Mitochondrial Mechanisms During Severe Polymicrobial Sepsis In The Rat, M. Chopra, H. B. Golden, S. Mullapudi, W. Dowhan, D. E. Dostal, Avadhesh C. Sharma Jan 2011

Modulation Of Myocardial Mitochondrial Mechanisms During Severe Polymicrobial Sepsis In The Rat, M. Chopra, H. B. Golden, S. Mullapudi, W. Dowhan, D. E. Dostal, Avadhesh C. Sharma

PCOM Scholarly Works

Background: We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Methodology/Principal Findings: Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD …


Rhoa/Rho-Kinase Signaling: A Therapeutic Target In Pulmonary Hypertension, Scott A. Barman, Shu Zhu, Richard E. White Jan 2009

Rhoa/Rho-Kinase Signaling: A Therapeutic Target In Pulmonary Hypertension, Scott A. Barman, Shu Zhu, Richard E. White

PCOM Scholarly Works

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of …


Duration Of Streptozotocin-Induced Diabetes Differentially Affects P38-Mitogen-Activated Protein Kinase (Mapk) Phosphorylation In Renal And Vascular Dysfunction, H. Chen, S. Brahmbhatt, A. Gupta, Avadhesh C. Sharma Jan 2005

Duration Of Streptozotocin-Induced Diabetes Differentially Affects P38-Mitogen-Activated Protein Kinase (Mapk) Phosphorylation In Renal And Vascular Dysfunction, H. Chen, S. Brahmbhatt, A. Gupta, Avadhesh C. Sharma

PCOM Scholarly Works

Background: In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta. Methods: Male Sprague Dawley rats (350-400 g) were randomized into three groups: sham (N = 6), 14-days diabetic (N = 6) and 28-days diabetic rats (N = 6). Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V.) on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were …