Medicine and Health Sciences Commons^™

Innate And Adaptive Immune System Consequences Of Post-Traumatic Stress Disorder, Tatlock H. Lauten, Tamara Natour, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked …

Leaky Gut And Inflammatory Biomarkers In A Medication Overuse Headache Model In Male Rats, Doğa Vuralli, Hale Gök Dağidir, Elif Abbasoğlu Topa, Hayrunnisa Bolay Belen

Turkish Journal of Medical Sciences

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs)are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are notcompletely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is toinvestigate the role of leaky gut and inflammation in an MOH model MOH model in male rats.Methods: The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronicNSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and …

High Amniotic Fluid Fractalkine And Mip-1Β Levels Are Associated With Intrauterine Growth Restriction: A Prospective Cohort Study, Şehmus Pala, Remzi Atilgan, Nevin İlhan

Turkish Journal of Medical Sciences

Proinflammatory chemokines have been shown to play crucial roles in implantation, spiral artery invasion, and thefetomaternal immunological response. In this context, we investigated the levels of fractalkine (CX3CL1) and chemokine CC motifligand 4 (CCL4 or MIP-1β) in maternal serum and amniotic fluids in pregnant women with intrauterine growth restriction (IUGR).Materials and methods: This prospective cohort study was carried out at Fırat University Obstetrics Clinic between January 1, 2022 andJuly 1, 2022. Group (G) 1: The control group consisted of 40 pregnant women who underwent elective cesarean section (CS) at 38–40weeks of gestation. G2: A total of 40 pregnant women with …

Impact Of Prolonged Exposure To Occasional And Regular Waterpipe Smoke On Cardiac Injury, Oxidative Stress And Mitochondrial Dysfunction In Male Mice, Naserddine Hamadi, Suhail Al-Salam, Sumaya Beegam, Nur Elena Zaaba, Ozaz Elzaki, Abderrahim Nemmar

All Works

Regular waterpipe smoking (Reg-WPS) is well recognized for its deleterious effect on the heart. However, there is a paucity of experimental studies on the impact of occasional waterpipe smoking (Occ-WPS), also known as nondaily smoking, versus Reg-WPS on cardiac homeostasis, and the mechanisms underlying these effects. Hence, we aimed, in the present study, to investigate the effect of Occ-WPS (30 min/day, 1 day/week) versus Reg-WPS (30 min/day, 5 days/week) for 6 months on systolic blood pressure (SBP), cardiac injury, oxidative markers, chemokines, proinflammatory cytokines, DNA damage and mitochondrial function compared with air (control) exposed mice. Our results show that SBP …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

The Gut Microbiome Modulates Associations Between Adherence To A Mediterranean-Style Diet, Abdominal Adiposity, And C-Reactive Protein In Population-Level Analysis, Amy Jennings, Tilman Kühn, Nicola P. Bondonno, Sabina Waniek, Corinna Bang, Andre Franke, Jan Kassubek, Hans-Peter Müller, Marcus Both, Katharina S. Weber, Wolfgang Lieb, Aedín Cassidy

Research outputs 2022 to 2026

Background: Adherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown. Objectives: To examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis. Design: In a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral …

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Changxu Fan, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Ting Wang, Marina Cella, William Vermi, Marco Colonna, Et Al.

2020-Current year OA Pubs

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt

The Evaluation Of Oxidative Stress And Inflammation Markers In Serum And Saliva Of The Patients With Temporomandibular Disorders, Di̇lara Kazan, Burcu Baş, Abdurrahman Aksoy, Enes Atmaca

Turkish Journal of Medical Sciences

Background/aim: Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant mechanisms and the accumulation of reactive oxygen species in tissues. This study was designed to compare salivary and serum OS and inflammation markers of individuals with TMD and healthy subjects. Materials and methods: A prospective cross-sectional study was conducted. Twenty-seven TMD patients diagnosed with disc displacement (DD) according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 17 healthy subjects were enrolled in the study. Prior to any treatment, serum, and saliva samples were taken from …

Protective Effects Of Swimming Exercises And Metformin On Cardiac And Aortic Damage Caused By A High-Fat Diet In Obese Rats With Type 2 Diabetes, By Regulating The Bcl2/Bax Signaling Pathway, Ebru Özüdoğru, Emrah Atay, Mehtap Savran, Hali̇l Aşci, Özlem Özmen, Şenay Topsakal

Turkish Journal of Medical Sciences

Background/aim: Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis. Materials and methods: Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), …

Different Roles Of Endothelial Cell-Derived Fibronectin And Plasma Fibronectin In Endothelial Dysfunction, Xiaoxin Luo, Weixiong Jian

Turkish Journal of Medical Sciences

MDABackground/ aim: Atherosclerosis is significantly influenced by endothelial cell activation and dysfunction. Studies have demonstrated the substantial presence of fibronectin (Fn) within atherosclerotic plaques, promoting endothelial inflammation and activation. However, cellular Fn (cFn) secreted by various cell types, including endothelial cells and smooth muscle cells, and plasma Fn (pFn) produced by hepatocytes. They are distinct forms of Fn that differ in both structure and function. The specific contribution of different types of Fn in promoting endothelial cell activation and dysfunction remain uncertain. Therefore, this study aimed to investigate the respective roles of pFn and endothelial cell-derived Fn (FnEC) in promoting …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Dna Methylation-Mediated Rbpjk Suppression Protects Against Fracture Nonunion Caused By Systemic Inflammation, Ding Xiao, Liang Fang, Zhongting Liu, Yonghua He, Jun Ying, Haocheng Qin, Aiwu Lu, Meng Shi, Tiandao Li, Bo Zhang, Jianjun Guan, Cuicui Wang, Yousef Abu-Amer, Jie Shen

2020-Current year OA Pubs

Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. To tackle the complexity and heterogeneity of the skeletal repair process, we performed single-cell RNA sequencing and revealed that progenitor cells were one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation of Rbpjk in fracture nonunion. We then validated the interplay between inflammation (via constitutive activation of Ikk2, Ikk2ca) and Rbpjk specifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identified Rbpjk as a direct target of Dnmt3b. Mechanistically, inflammation decreased Dnmt3b expression in progenitor cells, …

Exploring The Relationship Between Diabetes, Diabetes Risk, Depressive Symptoms, Chronic Stress, And Inflammatory Markers In Mexican-American Men, Aleli Fernandez

Open Access Theses & Dissertations

Background: Individuals with depression and stress are 60% more likely to develop type 2 diabetes compared to those without (Mezuk et al., 2008). Moreover, biological pro-inflammatory markers associated with psychosocial stress are risk factors for diabetes. Examining the relationship between psychological disorders, inflammation, and diabetes risk among MAH is important as they have high rates of diabetes.

Purpose: To examine the relationship between 1) depressive symptoms, chronic stress, and inflammatory markers, 2) inflammation and diabetes risk factors and 3) depression, stress, inflammation, diabetes risk, and metabolic syndrome (MetS).

Methods: A cross-sectional study of 100 adult men from El Paso, Texas …

Supra-Additive Effect Of Chronic Inflammation And Atherogenic Dyslipidemia On Developing Type 2 Diabetes Among Young Adults: A Prospective Cohort Study, Yulong Lan, Dan Wu, Zhiwei Cai, Yuancheng Xu, Xiong Ding, Weiqiang Wu, Shaocong Lan, Lan Chen, Zheng Guo, Lois Balmer, Xingang Li, Manshu Song, Shouling Wu, Jingli Gao, Wei Wang, Youren Chen

Research outputs 2022 to 2026

Background: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. Methods: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). Results: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident …

The Relationship Between Clinical Phenotype And Kallikrein-Kinin Bioregulation In Different Forms Of Arthritis, Dino B. A. Tan, Chantalia Tedja, Lukas Kuster, Warren D. Raymond, Andreea Harsanyi, Priya V. Chowalloor, Neil L. Misso, Shashi Argawal, Kanti D. Bhoola, Helen I. Keen

Research outputs 2022 to 2026

Objective: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. Methods: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization …

Combined Effect Of Adiposity And Elevated Inflammation On Incident Type 2 Diabetes: A Prospective Cohort Study, Dan Wu, Yulong Lan, Shuohua Chen, Xiong Ding, Guanzhi Chen, Chutao Wu, Lois Balmer, Wencan Xu, Shouling Wu, Wei Wang

Research outputs 2022 to 2026

Background: Adiposity and elevated inflammation are two hallmarks of hyperglycemia. However, it is unknown whether clustering of elevated inflammation and adiposity interact act on diabetogenesis and lead to a greater risk for incident type 2 diabetes (T2D). Methods: Adiposity was indicated by body mass index, waist circumference and ultrasonography-measured fatty liver degrees. Elevated inflammation was indicated as high-sensitivity C-reactive protein levels ≥ 2 mg/L. Time-to-event survival analyses were conducted to investigate the joint effect of adiposity and inflammation on incident T2D on both multiplicative and additive scales. Results: Among 82,172 non-diabetic participants from a prospective cohort in China, 14,278 T2D …

Gut Microbiota Induces Weight Gain And Inflammation In The Gut And Adipose Tissue Independent Of Manipulations In Diet, Genetics, And Immune Development, Devesha H Kulkarni, Brigida Rusconi, Alexandria N Floyd, Elisabeth L Joyce, Khushi B Talati, Hrishi Kousik, Dereck Alleyne, Dalia L Harris, Lorena Garnica, Ryan Mcdonough, Shay S Bidani, Hrishikesh S Kulkarni, Elizabeth P Newberry, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Obesity and the metabolic syndrome are complex disorders resulting from multiple factors including genetics, diet, activity, inflammation, and gut microbes. Animal studies have identified roles for each of these, however the contribution(s) specifically attributed to the gut microbiota remain unclear, as studies have used combinations of genetically altered mice, high fat diet, and/or colonization of germ-free mice, which have an underdeveloped immune system. We investigated the role(s) of the gut microbiota driving obesity and inflammation independent of manipulations in diet and genetics in mice with fully developed immune systems. We demonstrate that the human obese gut microbiota alone was sufficient …

Social Capital Associates With Better Cognitive Health, Oral Health And Epigenetic Age Deceleration: Findings From The Canadian Longitudinal Study On Aging., Aileen Liang, Noha Gomaa

Department of Medicine Publications

Background: Social exposures are linked to an array of health outcomes, especially around aging. In this study, we examined the association of social capital, defined as social relationships and networks, with clinical and biological outcomes including cognitive health, oral inflammation, and epigenetic aging. Methods: We used data from the Canadian Longitudinal Study on Aging (CLSA) (n =1,479; aged 45–85 years), categorizing social capital as structural and cognitive capital. Oral inflammation was determined as the presence of gum bleeding. Epigenetic aging was computed as the difference between chronological age and DNA methylation age. We constructed multivariable regression models adjusted for covariates …

The Effects Of Initiating A Fast With A High Fat Or A High Carbohydrate Shake On Mcp-1, Tnf-Alpha, And Il-6 Levels, Gage Jensen, Bruce Bailey

International Journal of Exercise Science: Conference Proceedings

Alzheimer’s disease, stroke, heart disease, and diabetes all rank among the leading causes of death in the United States, particularly among the elderly. While many behavioral and pharmacological strategies have been employed to reduce the incidence of these conditions, increasing evidence indicates that entering a mild to moderate state of ketosis through fasting or a very low carbohydrate diet can improve the prognosis for these conditions. PURPOSE: The purpose of this study was to evaluate the extent to which a high carbohydrate low fat (HC/LF) pre-fast meal altered MCP-1, TNF-alpha and IL-6 compared to a low carbohydrate high-fat pre-fast …

Current Medical Therapy And Revascularization In Peripheral Artery Disease Of The Lower Limbs: Impacts On Subclinical Chronic Inflammation, Andrea Leonardo Cecchini, Federico Biscetti, Matteo Manzato, Lorenzo Lo Sasso, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Luis Eraso, Paul Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Peripheral artery disease (PAD), coronary artery disease (CAD), and cerebrovascular disease (CeVD) are characterized by atherosclerosis and inflammation as their underlying mechanisms. This paper aims to conduct a literature review on pharmacotherapy for PAD, specifically focusing on how different drug classes target pro-inflammatory pathways. The goal is to enhance the choice of therapeutic plans by considering their impact on the chronic subclinical inflammation that is associated with PAD development and progression. We conducted a comprehensive review of currently published original articles, narratives, systematic reviews, and meta-analyses. The aim was to explore the relationship between PAD and inflammation and evaluate the …

Dysregulated Cd200-Cd200r Signaling In Early Diabetes Modulates Microglia-Mediated Retinopathy, Charles W Pfeifer, James T Walsh, Andrea Santeford, Joseph B Lin, Wandy L Beatty, Ryo Terao, Yizhou A Liu, Keitaro Hase, Philip A Ruzycki, Rajendra S Apte

2020-Current year OA Pubs

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R …

Infection And Inflammation Stimulate Expansion Of A Cd74+ Paneth Cell Subset To Regulate Disease Progression, Iyshwarya Balasubramanian, Shengxiang Sun, Ta-Chiang Liu, Et Al.

2020-Current year OA Pubs

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74

T Cell Control Of Inflammaging, Irina Shchukina, Pavla Bohacova, Maxim N Artyomov

2020-Current year OA Pubs

T cells are a critical component of the immune system, found in abundance in blood, secondary lymphoid organs, and peripheral tissues. As individuals age, T cells are particularly susceptible to changes, making them one of the most affected immune subsets. These changes can have significant implications for age-related dysregulations, including the development of low-grade inflammation - a hallmark of aging known as inflammaging. In this review, we first present age-related changes in the functionality of the T cell compartment, including dysregulation of cytokine and chemokine production and cytotoxicity. Next, we discuss how these changes can contribute to the development and …

The Role Of Inflammation In Age-Related Macular Degeneration, Diana Florina Tricorache, Ana Maria Dascalu, Crenguta Serboiu, Anca Bobirca, Dragos Cretoiu, Dan Bratu, Corneliu Tudor, Laura Carina Tribus

Journal of Mind and Medical Sciences

Age-related macular degeneration (AMD) is a complex, chronic, and progressive disease which affects the macular area, being one of the leading causes of irreversible vision loss worldwide. Specific alterations of retinal structure occur at the macular level, which regarding its severity can range from the presence of drusen to the development of geographic atrophy or choroidal neovascularization. AMD has long been considered a degenerative disease, but new studies highlight the role of inflammation present both in the atrophic form and in the exudative form. The present review is based on comprehensive research on PubMed and Web of Science databases, and …

Serotonin Reduction In Post-Acute Sequelae Of Viral Infection, Andrea Wong, Ashwarya Devason, Iboro Umana, Timothy Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke Izzo, Jihee Kim, Monika Tetlak, Hélène Descamps, Simone Park, Stephen Wisser, Aaron Mcknight, Ryan Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean-Christophe Beltra, Michaël Michieletto, Shin Foong Ngiow, Brittany Miller, Megan Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex Huber, Peter Hewins, Christopher Petucci, Candice Chu, Gwen Baraniecki-Zwil, Leila Giron, Amy Baxter, Allison Greenplate, Charlotte Kearns, Kathleen Montone, Leslie Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie Jurado, Kathryn Wellen, Una O'Doherty, Mohamed Abdel-Mohsen, Alan L Landay, Ali Keshavarzian, Timothy Henrich, Steven Deeks, Michael Peluso, Nuala Meyer, E. John Wherry, Benjamin Abramoff, Sara Cherry, Christoph Thaiss, Maayan Levy

Department of Microbiology and Immunology Faculty Papers

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, …

Early Resveratrol Treatment Mitigates Joint Degeneration And Dampens Pain In A Mouse Model Of Pseudoachondroplasia (Psach), Jacqueline T Hecht, Alka C Veerisetty, Debabrata Patra, Mohammad G Hossain, Frankie Chiu, Claire Mobed, Francis H Gannon, Karen L Posey

2020-Current year OA Pubs

Pseudoachondroplasia (PSACH), a severe dwarfing condition associated with early-onset joint degeneration and lifelong joint pain, is caused by mutations in cartilage oligomeric matrix protein (COMP). The mechanisms underlying the mutant-COMP pathology have been defined using the MT-COMP mouse model of PSACH that has the common D469del mutation. Mutant-COMP protein does not fold properly, and it is retained in the rough endoplasmic reticulum (rER) of chondrocytes rather than being exported to the extracellular matrix (ECM), driving ER stress that stimulates oxidative stress and inflammation, driving a self-perpetuating cycle. CHOP (ER stress signaling protein) and TNFα inflammation drive high levels of mTORC1 …

Editorial: Debates In Cardiovascular Pharmacology And Drug Discovery: 2022, Keman Xu, Fatma Saaoud, Ying Shao, Yifan Lu, Xiaohua Jiang, Sheng Wu, Jianxin Sun, Filipe Fernades Conti, Laisel Martinez, Roberto Vazquez-Padron, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

No abstract provided.

Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD …

Reduction Of Sparc Protects Mice Against Nlrp3 Inflammasome Activation And Obesity, Seungjin Ryu, Olga Spadaro, Sviatoslav Sidorov, Aileen H. Lee, Sonia Caprio, Christopher Morrison, Steven R. Smith, Eric Ravussin, Irina Shchukina, Maxim N. Artyomov, Yun-Hee Youm, Vishwa Deep Dixit

2020-Current year OA Pubs

The comprehensive assessment of long-term effects of reducing intake of energy (CALERIE-II; NCT00427193) clinical trial established that caloric restriction (CR) in humans lowers inflammation. The identity and mechanism of endogenous CR-mimetics that can be deployed to control obesity-associated inflammation and diseases are not well understood. Our studies have found that 2 years of 14% sustained CR in humans inhibits the expression of the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), in adipose tissue. In mice, adipose tissue remodeling caused by weight loss through CR and low-protein diet feeding decreased, while high-fat diet-induced (HFD-induced) obesity increased SPARC expression …

Exploring The Role Of 4-Thiazolidinone Derivatives As Potential Cox-2 Inhibitors And Free Radical Scavenging Agents, Vikram Jeet Singh, Pooja Chawla

Research Symposium

Background: Cyclooxygenase-2 (COX-2) and free radicals has become an important target in the management of various pathological conditions including cancer and inflammation. The pyridine or thiazolidinone has become an emerging scaffold in the drug design and development of COX-2 inhibitors and free radical scavenging agents. 4-Thiazolidinone clubbed pyridine may potentiate each other activity and can emerge as a promising scaffold in the treatment of inflammation/cancer.

Methods: The present work reports synthesis and screening of 4-thiazolidinone-pyridine hybrids with substituted arylidene containing electron-donating group at 5^th position. The compounds were screened for their in-vivo anti-inflammatory activity using carrageenan-induced rat …