Medicine and Health Sciences Commons^™

Single-Cell Transcriptomics Reveals Pre-Existing Covid-19 Vulnerability Factors In Lung Cancer Patients, Wendao Liu, Wenbo Li, Zhongming Zhao

Journal Articles

UNLABELLED: Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory …

Antagomir Treatment For Deep-Space Simulated Changes In The Liver Of Mice, Natalie P. Hayslip

Honors Undergraduate Theses

With the start of NASA’s Artemis program, astronauts will soon leave the protection of Earth’s magnetosphere. Previous studies have established a theme of liver dysregulation associated with the harmful radiation and microgravity experienced in deep space. MicroRNAs (miRNAs) are key regulators of many of the pathologies observed during and after spaceflight, including hepatic fibrosis, making them strong potential biomarkers and therapeutic targets. Therefore, in the present study we investigated the effects of simulated microgravity, galactic cosmic radiation (GCR), and solar particle events (SPE) on miRNAs and mRNAs involved in the TGF-β signaling pathway, a key regulator of fibrosis, senescence, and …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Jingjing Huang, Hydia Puente, Nancy E Wareing, Minghua Wu, Maureen D Mayes, Harry Karmouty-Quintana, Shervin Assassi, Tingting W Mills

Journal Articles

Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)-4 and - 13 contribute to the pathogenesis of skin fibrosis by promoting collagen production and myofibroblast differentiation. Signal transducers and activators of transcription 6 (STAT6) is one of the most important downstream transcription factors activated by both IL-4 and IL-13. However, it is not completely understood whether STAT6 plays a role during the pathogenesis of skin fibrosis in SSc. In this study, we observed increased STAT6 phosphorylation in fibrotic skin samples collected …

Gpcrs And Fibroblast Heterogeneity In Fibroblast-Associated Diseases, Nidhi V. Dwivedi, Souvik Datta, Karim El-Kersh, Ruxana Sadikot Md, Mrcp, Apar Kishor Ganti, Surinder K. Batra, Maneesh Jain

Journal Articles: Biochemistry & Molecular Biology

G protein-coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of "most targeted receptors". About one-third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic …

Chronic Circadian Disruption Increases Risk For Cardiovascular Disease, Jazmine I Benjamin

All ETDs from UAB

Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. …

Role Of Endosialin/Cd248 And Cytoglobin In Liver Fibrosis, Mahmoud Abdallah Mansour, Khaled Abd Elazeme Eid, Ashraf Mohamed Elkabeer, Eglal Mohamed Kenawy, Bakheet Elkot Mostafa Elsadek

Al-Azhar International Medical Journal

Background - Chronic liver diseases are a major global health burden. CYGB, Human IV globin is abundantly expressed in Hepatic Stellate Cell(HSCs) between hepatocytes. CYGB can bind oxygen and nitric oxide and is said to protect HSCs from reactive oxygen species(ROS).

Aim - to estimate role of CD248 and Cygb in process of liver fibrosis.

Patients and Methods - This study was conducted on forty-four Egyptian patients with hepatic stenosis detected by ultrasound, and forty healthy volunteers as control group.

Results - Our results showed statistical significant (p-value < 0.001) increased CD248 in patients group (189.03 ± 66.6) when compared with control group (138.7 ± 36.5), decreased Cygb in patients group (1.62 ± 0.35) when compared with control group (1.93 ± 0.26)

Conclusion - Our study identified Cygb and CD248 …

The Pro-Fibrotic Response To Lens Injury Is Signaled In A Pi3k Isoform-Specific Manner, A. Sue Menko, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as …

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system^1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas³, an excessive and/or prolonged immune response¹, the activation and proliferation of fibrosis-inducing progenitor cells⁴, and a pro-fibrotic extra-cellular microenvironment⁵. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

Reno-Protective And Immune Effects Of Growth Differentiation Factor 15 In Obesity-Related Kidney Disease, Jessie T. Sullivan

Honors Thesis

According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have …

The Pro-Fibrotic Response Of Mesenchymal Leader Cells To Lens Wounding Involves Hyaluronic Acid, Its Receptor Rhamm, And Vimentin, A. Sue Menko, Alison Romisher, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hyaluronic Acid/Hyaluronan (HA) is a major component of the provisional matrix deposited by cells post-wounding with roles both in regulating cell migration to repair a wound and in promoting a fibrotic outcome to wounding. Both are mediated through its receptors CD44 and RHAMM. We now showed that HA is present in the provisional matrix assembled on the substrate surface in a lens post-cataract surgery explant wound model in which mesenchymal leader cells populate the wound edges to direct migration of the lens epithelium across the adjacent culture substrate onto which this matrix is assembled. Inhibiting HA expression with 4-MU blocked …

Interstitial Lung Disease In Patients With Systemic Lupus Erythematosus: A Cohort Study, Naci̇ Şenkal, Esen Kiyan, Ali̇ Aslan Demi̇r, Yasemi̇n Yalçinkaya, Ahmet Gül, Murat İnanç, Mahdume Lale Öçal, Bahar Artim Esen

Turkish Journal of Medical Sciences

Background/aim: Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of organ/system involvement. Respiratory system involvement is common in these patients and usually manifests itself by disorders of the lung parenchyma, pleura, pulmonary vasculature or diaphragm. In this study, we sought to determine the frequency of interstitial lung disease (ILD) in patients with SLE and associated risk factors. Materials and methods: Three hundred randomly chosen patients with SLE were included. Chest x-ray (CXR), lung spirometry and carbon monoxide diffusion test (DLCO) were performed. High-resolution thorax computed tomography (HRCT) was performed for a definite diagnosis of ILD. Results: Of …

Mast Cell Involvement In Fibrosis In Chronic Graft-Versus-Host Disease, Ethan Strattan, Gerhard Carl Hildebrandt

Markey Cancer Center Faculty Publications

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead …

Radiation Induces Metabolic Dysregulation In Pulmonary Fibroblasts, Josly Pierre-Louis, Margaret A. T. Freeberg, Jane K. Rebman, Thomas H. Thatcher, Patricia J. Sime

Graduate Research Posters

Rationale: Exposure of the lung to ionizing radiation, such as during radiotherapy, can result in pulmonary fibrosis (PF), which has few treatment options. PF is characterized by an accumulation of extracellular matrix proteins that form scar tissue, resulting in dyspnea, disruption of gas exchange, and even death. We and others have shown that metabolic reprogramming is a hallmark of idiopathic pulmonary fibrosis (IPF). IPF lung tissue, and lung fibroblasts treated with TGF-β, exhibit increased aerobic glycolysis with increased expression of lactate dehydrogenase A (LDHA) and excess production of lactate, leading to reduced extracellular pH that activates latent TGF-β. Here, we …

The Prevalence Of Sjögren's Syndrome And Sicca Symptoms In Patients With Systemicsclerosis And Alpha-Smooth Muscle Actin Expression In Biopsy Specimens From Minorsalivary Glands, Gerçek Can, Sülen Sarioğlu, Ahmet Meri̇h Bi̇rli̇k, Gökçe Kenar, Özgül Soysal Gündüz, Di̇lek Solmaz, Vedat Gerdan, Fatoş Önen, Nurullah Akkoç, Servet Akar

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the prevalence of sicca symptoms and secondary Sjögren's syndrome (SjS) in patients with systemic sclerosis (SSc). Also this study aimed to evaluate the expression of ∝ -smooth muscle actin (∝ -SMA) in minor salivary gland (MSG) specimens, a possible marker of fibrosis responsible for myofibroblastic transformation. Materials and methods: Patients with SSc who were followed in Rheumatology outpatient clinic at a university hospital evaluated. The questionnaire of sicca symptoms and classification of SjS were evaluated according to the American-European Consensus Group (AECG) criteria. Histopathologic evaluations were done in MSG specimens investigating the presence of …

Trypanosoma Cruzi Modulates Piwi-Interacting Rna Expression In Primary Human Cardiac Myocytes During The Early Phase Of Infection, Kayla J. Rayford, Ayorinde Cooley, Ashutosh Arun, Girish Rachakonda, Yulia Kleschenko, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Pius N. Nde

Publications and Research

Trypanosoma cruzi dysregulates the gene expression profile of primary human cardiomyocytes (PHCM) during the early phase of infection through a mechanism which remains to be elucidated. The role that small non-coding RNAs (sncRNA) including PIWI-interacting RNA (piRNA) play in regulating gene expression during the early phase of infection is unknown. To understand how T. cruzi dysregulate gene expression in the heart, we challenged PHCM with T. cruzi trypomastigotes and analyzed sncRNA, especially piRNA, by RNA-sequencing. The parasite induced significant differential expression of host piRNAs, which can target and regulate the genes which are important during the early infection phase. An …

The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko

All ETDs from UAB

Acute myocardial infarction (MI) produces massive, sudden cardiomyocyte death, triggering an inflammatory and healing response that initially leads to scar formation and ultimately may induce progressive ischemic cardiomyopathy and heart failure (HF). Scar formation and left ventricular (LV) hypertrophy occur in response to MI to stabilize injury compensating for lost myocardial function. Over time, heart function can become decompensated due to neuroendocrine dysfunction and adverse LV remodeling, ultimately leading to HF. Adverse remodeling is characterized by continued dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammation. Studies have documented a resurgence in inflammatory cytokines and infiltrating leukocytes after resolution of the …

Characterization Of Wilms' Tumour 1 (Wt1) As A Biomarker For Fibrosis In Duchenne Muscular Dystrophy, Patrick Murphy

Electronic Thesis and Dissertation Repository

Duchenne muscular dystrophy (DMD) is the most common inherited pediatric muscle dystrophy. It is characterized by muscle degeneration, resulting in fibrosis that is a significant impediment to both endogenous muscle repair and any potential regenerative strategy. At present, there are few therapies that specifically address fibrosis and microenvironment improvement, but one possibility rests in targeting the Wilms’ tumour 1 (Wt1) protein. Wt1 is a zinc finger transcription factor, recently shown to be expressed in fibrotic conditions such as Dupuytren’s disease and pulmonary fibrosis. This thesis examines the expression pattern of Wt1 in several mouse models of DMD, through both histological …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Jiang Liu

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Zijian Xie

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Yanling Yan

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Joseph I Shapiro MD

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

The Trade-Off Between Dietary Salt And Cardiovascular Disease; A Role For Na/K-Atpase Signaling?, Joe X. Xie, Anna Pearl Shapiro, Joseph I. Shapiro Md

Joseph I Shapiro MD

It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathways. This review will discuss the mechanism of CTS in renal sodium handling and a potential “trade-off” effect from their role in inducing tissue fibrosis.

Effect Of Stem Cell And Vitamin E For The Reduction Of Liver Fibrosis, Sulaiman Shams, Salman Khan, Muhammad Ayaz, Haider Ali Khan, Hammad Hassan

Centre for Regenerative Medicine & Stem Cell Research

Liver disease is seventh leading cause of death worldwide. In the past, liver transplantation was thought to be the only treatment for the last stage liver disease but currently stem cells therapy is an alternative method for the treatment of liver disease. So mesenchymal stem cells (MSCs) transplantation is one of the best tool for treatment of liver disease. The aim of the current study was to investigate the combined effect of vitamin E (Vit E) and MSCs on liver fibrosis. Liver damage was induced in male albino mice intraperitoneally with carbon tetrachloride (CCl4) twice a week for six weeks. …

Calpain Inhibition Attenuates Adipose Tissue Inflammation And Fibrosis In Diet-Induced Obese Mice, Latha Muniappan, Aida Javidan, Weihua Jiang, Shayan Mohammadmoradi, Jessica J. Moorleghen, Wendy S. Katz, Anju Balakrishnan, Deborah A. Howatt, Venkateswaran Subramanian

Saha Cardiovascular Research Center Faculty Publications

Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. …

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …

Pentoxifylline Attenuates Mucosal Damage In An Experimental Model Of Rat Colitis By Modulating Tissue Biomarkers Of Inflammation, Oxidative Stress, And Fibrosis, Eylem Karatay, Özlem Gül Utku, Harun Erdal, Mehmet Arhan, İbrahi̇m Koral Önal, Mehmet İbi̇ş, Özgür Eki̇nci̇, Canan Yilmaz Demi̇rtaş, Gi̇yaseddi̇n Şükrü Dumlu

Turkish Journal of Medical Sciences

Background/aim: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and methods: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days. Results: IP and IR …

Histopathological Effects Of Mesenchymal Stem Cells In Ratswith Bladder And Posterior Urethral Injuries, Berat Di̇lek Demi̇rel, Ünal Biçakci, Riza Rizalar, Ferda Alpaslan Pinarli, Oğuz Aydin

Turkish Journal of Medical Sciences

Background/aim: To evaluate the effects of mesenchymal stem cell (MSC) therapy in an experimental bladder and posterior urethral injury model. Materials and methods: The study subjects consisted of 40 male Wistar albino rats that were divided into four groups: control group (n = 10) (the bladder was only surgically opened and closed), sham group (n = 10) (surgical procedure), IVMSC group (n= 10) (surgical procedure and intravenous MSC treatment), and LMSC group (n = 10) (surgical procedure and local MSC treatment). Histopathological evaluation was performed for the degree of fibrosis and inflammation and the extent and intensity of staining of …