Medicine and Health Sciences Commons^™

Measurement Of Cumulative High-Sensitivity C-Reactive Protein And Monocyte To High-Density Lipoprotein Ratio In The Risk Prediction Of Type 2 Diabetes: A Prospective Cohort Study, Dan Wu, Genyuan Chen, Yulong Lan, Shuohua Chen, Xiong Ding, Chiju Wei, Lois Balmer, Wei Wang, Shouling Wu, Wencan Xu

Research outputs 2022 to 2026

Background: Converging data have suggested that monocytic inflammation and C-reactive protein (CRP) are biologically intertwined processes and are involved in diabetogenesis. This study aimed to investigate the association between systemic inflammation assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP) and monocyte to high-density lipoprotein ratio (CumMHR) and incident type 2 diabetes (T2D) and their predictive value for T2D in a general population. Methods: A total of 40,813 nondiabetic participants from a prospective real-life cohort (Kailuan Study, China) were followed biennially from 2010/2011 until December 31, 2020. Multivariable Cox regression analyses were conducted to evaluate the adjusted hazard ratios (aHRs) of …

Chronic Stress-Induced Neuroinflammation: Relevance Of Rodent Models To Human Disease., Abigail G White, Elias Elias, Andrea Orozco, Shivon A Robinson, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a …

Development Of A Synthetic Biomarker System For Early Detection Of Ischemic Stroke, Mason L. Matthies

Honors Thesis

Stroke, particularly Ischemic Stroke (IS) affects millions of individuals across the world each year . Current diagnostic methods like CT scans and MRI imaging have limitations in detecting minor IS due to the limited spatial resolution of the CT scan and the feasibility and access to MRIs warranting a more effective method of early detection. Natural biomarkers are currently ineffective in detecting IS prior to severe damage like rapid cell death (32,000 cells/sec) post arterial blockage because there is minimal amount of natural biomarkers expressed from minor cellular damage . Our proposed Synthetic Biomarker System (SBS) would solve this by …

Preventing Postoperative Cognitive Dysfunction Through Preoperative Exercise, John Andre Socci

Rowan-Virtua Research Day

Introduction: Postoperative cognitive dysfunction (POCD) is a common problem in the elderly population after undergoing anesthesia that results in sometimes irreversible cognitive and physical impairment that can increase mortality and decrease quality of life.

Methods: To see the relationship between preoperative fitness capacity and how this relates to postoperative cognitive ability a literature review was performed. Studies that were included involved populations older than sixty years old that had undergone anesthesia. Additionally, animal studies were included to show inflammatory marker levels and how they increased in relation to physical activity.

Results: Various fitness scales were used such as the Timed …

The Neuroprotective Role Of Lipoxin A4 In Reinstating Blood Brain Barrier Integrity In Neuroinflammatory Disease Processes, Minjal Patel, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB), formed by the vascular endothelium, astrocytic foot processes, pericytes, is a highly selective barrier that is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI).¹ Loss of BBB integrity leads to the proliferation of pro-inflammatory cytokines, including TNFɑ, IL-1β, and IL-6.² Moderate inflammation has a beneficial response in the system following an acute injury. However, prolonged inflammation has been known to perturb homeostasis and have …

The Effects Of Sglt2 Inhibitors In Patients With Metabolic Dysfunction-Associated Fatty Liver Disease; A Narrative Review, Mihaela Simona Popoviciu, Lorena Paduraru, Mominur Rahman, Fatema Akter Supti, Roxana Adriana Stoica, Delia Reurean Pintilei, Cristina Ioana Bica, Simona Cavalu

Journal of Mind and Medical Sciences

Worldwide, metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant public health concern, especially since more than fifty percent of people with type 2 diabetes are affected by it. This pathological condition includes all states of fatty liver disease, from non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). Prolonged evolutions can lead to cirrhosis and cancer, so treatment must be started early. Hepatic steatosis may be improved by sodium glucose co-transporter 2 inhibitors (SGLT2 inhibitors), which prevent glucose reabsorption in the proximal renal tubule and increase urinary excretion, thus lowering plasma glucose levels. Experimental studies in animal models have suggested …

Correlation Between Periodontal Status And Parkinson's Disease; A Literature Review, Dragos Nicolae Ciongaru, Anca Silvia Dumitriu, Bogdan Alexandru Dimitriu, Stana Paunica, Marina Cristina Giurgiu, Brandusa Florina Mocanu, George Alexandru Popescu, Silviu Mirel Pituru

Journal of Mind and Medical Sciences

This systematic review aims to explore the relationship between chronic inflammation of periodontal disease and neurodegenerative disorders (especially Parkinson's disease), focusing primarily on pathophysiological, clinical and immunological aspects. An exhaustive search on this topic was performed in several databases (including PubMed, Scopus and Web of Science) selecting articles published between 2006 and 2023. After reviewing the titles, abstracts and protocols of each study, 13 articles were extracted for detailed assessment. The main indicators in the study included clinical signs of gingival inflammation, bleeding on probing (BoP), bone loss (BL), periodontal probing depth (PPD), and clinical attachment loss (CAL). Additionally, levels …

The Role Of Inflammation In Diabetic Retinopathy In Patients With Type Ii Diabetes; Potential Therapeutic Perspectives, Adriana Georgescu, Ana Dascalu, Daniela Stana, Cristina Alexandrescu, Anca Bobirca, Bogdan Mihai Cristea, Geta Vancea, Crenguta Sorina Serboiu, Dragos Serban, Corneliu Tudor, Andreea Letitia Arsene, Laura Carina Tribus

Journal of Mind and Medical Sciences

Diabetic retinopathy is one of the major causes of visual impairment and blindness in adult population. The pathology is complex, the metabolic changes induced by the hyperglycemic environment leading to neurodegeneration, microvascular damage, with secondary ischemic and inflammatory changes in the retina. This review aims to update the literature data related to the role of inflammation in the onset and progression of diabetic retinopathy. Thus, the molecular and biochemical mechanisms triggered by excess glucose increase the expression of genes involved in inflammatory processes, which leads to the synthesis of inflammatory cytokines such as Il1, Il6, TNF alpha as well as …

Coronary Microvascular Dysfunction In Childhood: An Emerging Pathological Entity And Its Clinical Implications, Takeshi Tsuda, Gina Patel

Department of Pediatrics Faculty Papers

Coronary microvascular dysfunction (CMD) encompasses a spectrum of structural and functional alterations in coronary microvasculature resulting in impaired coronary blood flow and consequent myocardial ischemia without obstruction in epicardial coronary artery. The pathogenesis of CMD is complex involving both functional and structural alteration in the coronary microcirculation. In adults, CMD is predominantly discussed in context with anginal chest pain or existing ischemic heart disease and its risk factors. The presence of CMD suggests increased risk of adverse cardiovascular events independent of coronary atherosclerosis. Coronary microvascular dysfunction is also known in children but is rarely recognized due to paucity of concommitent …

Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele

2020-Current year OA Pubs

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, …

Relationship Between C-Reactive Protein/Albumin Ratio And Mucocutaneous Symptom Frequency And Disease Severity In Behçet’S Disease, Erdal Pala, Mustafa Bayraktar

Turkish Journal of Medical Sciences

Background/aim: There is no specific marker that can be applied to determine the severity of Behçet’s disease. The aim of this study is to investigate the potential of C-reactive protein (CRP)/albumin (CAR) ratio as a tool for assessing the severity of Behçet’s disease.Materials and methods: A retrospective crosssectional study was conducted by examining hospital archives. The CRP and albumin levels of Behçet’s disease patients who presented to our dermatology clinic over a three-year period from February 2020 to February 2022 were included, along with the identical laboratory parameters in the control group. The CAR ratio was calculated and statistically compared …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Journal Articles

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Role Of Mechanoregulation In Mast Cell-Mediated Immune Inflammation Of The Smooth Muscle In The Pathophysiology Of Esophageal Motility Disorders, Raj Goyal, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Major esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated with smooth muscle hypertrophy and hypercontractility, whose cause is unknown. This review investigated immune inflammation in the causation of smooth muscle changes in obstructive esophageal bolus transport. Findings suggest that …

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as …

Amniotic Bladder Therapy In Patients With Interstitial Cystitis/Bladder Pain Syndrome, Jack Considine, Codrut Radoiu, Sophie Wittenberg, Nivedita Dhar Md, Raghav Madan Md, Jack Vernocke Md, Aron Liaw Md, Alaa Hamada Md

Medical Student Research Symposium

Introduction and Objectives: Our study hypothesis postulates that if patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) bladders exhibit increased inflammation, fibrosis, and urothelial dysfunction, then treatment modalities that modulate inflammation and fibrosis, while promoting a regeneration may have a therapeutic effect in such patients. Amniotic membrane (AM) has been shown to foster a regenerative wound-healing environment. This study investigates the safety and efficacy of bladder injections of AM in patients with treatment resistant IC/BPS.

Methods: Fifteen consecutive treatment resistant IC/BPS patients (mean age 50.7 ± 14.4 years) with a median disease duration of 7 years (5-12 years) were …

Chronic Glp1 Therapy Reduces Postprandial Il6 In Obese Humans With Prediabetes, Vala Hamidi, Hongyu Wang, Vi Pham, Karla Bermudez Saint Andre, Heinrich Taegtmeyer, Absalon D Gutierrez

Journal Articles

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty …

Chronic Glp1 Therapy Reduces Postprandial Il6 In Obese Humans With Prediabetes, Vala Hamidi, Hongyu Wang, Vi Pham, Karla Bermudez Saint Andre, Heinrich Taegtmeyer, Absalon D Gutierrez

Journal Articles

Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty …

The Paradigm Change From Reactive Medical Services To 3pm In Ischemic Stroke: A Holistic Approach Utilising Tear Fluid Multi-Omics, Mitochondria As A Vital Biosensor And Ai-Based Multi-Professional Data Interpretation, Olga Golubnitschaja, Jiri Polivka Jr, Pavel Potuznik, Martin Pesta, Ivana Stetkarova, Alena Mazurakova, Lenka Lackova, Peter Kubatka, Martina Kropp, Gabriele Thumann, Carl Erb, Holger Fröhlich, Wei Wang, Babak Baban, Marko Kapalla, Niva Shapira, Kneginja Richter, Alexander Karabatsiakis, Ivica Smokovski, Leonard C. Schmeel, Eleni Gkika, Friedemann Paul, Paolo Parini, Jiri Polivka

Research outputs 2022 to 2026

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990–2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal …

Health-Promoting Benefits Of Lentils: Anti-Inflammatory And Anti-Microbial Effects, Rachel Alexander, Abdullah Khaja, Nicholas Debiec, Alex Fazioli, Mary Torrance, Mohammed S. Razzaque

School of Medicine Publications and Presentations

This paper describes how lentils (Lens culinaris species) can positively affect health by reducing inflammation, providing antioxidants, and displaying antimicrobial properties. Lentils are rich in proteins, essential amino acids, minerals, and fibers, making them a valuable source of nutrition, particularly in low and middle-income countries. Lentils have many health benefits, including positive effects on diabetes management, support for cardiovascular health, and antioxidative properties. The antioxidative properties of lentils, attributed to their phenolic content, and their ability to inhibit inflammation-related enzymes are also discussed. We discuss the potential of lentils as a dietary tool in promoting immunity, reducing disease burdens, …

Salivary C-Reactive Protein And Cortisol Analysis In Collegiate Female Lacrosse Athletes During A 2-Game Week, Kelsi R. Lambright, Stephanie Mathews, Jennifer A. Bunn

International Journal of Exercise Science: Conference Proceedings

Cortisol (CORT) and C-reactive protein (CRP) are two indicators of stress and are linked to tissue inflammation and illness. Increased stress and inflammation have been shown to decrease cognitive functioning, leading to diminished performance for athletes. Subjectively, athletes indicate fluctuations in stress, but few studies have assessed the physiological response of training and competition in elite female athletes. PURPOSE: The primary aim was to assess the acute response of CORT and CRP in Division I female lacrosse athletes during a high-stress week, including two games and three practices during the competitive season. The secondary aim was to assess the …

Short-Term Cd8+ T Cell Depletion Results In Blunted Liver Inflammation In Old Mice, Konner J. Terrebonne, David J. Buckley, Blessy Joseph, Sunita Sharma, Daniel W. Trott

International Journal of Exercise Science: Conference Proceedings

Advanced age is associated with an increase in basal inflammation of the organs. Previously we have found that T cells accumulate in the liver of old mice. A large proportion of these cells are CD8+ and produce inflammatory cytokines. We have previously demonstrated that CD8+ T cell depletion results in improved glucose tolerance in old mice. However, the mechanisms by which CD8+ depletion improves glucose tolerance is unclear. Therefore, we sought to determine whether pharmacologic CD8+ depletion would result in decreased liver specific inflammation in old mice compared to their old CD8+ intact counterparts. PURPOSE: To test the hypothesis …

Firefighters Versus Law Enforcement Officers: A Comparison Of Cardiovascular Disease Risk, Bethany C. Guerra, Hunter Martaindale, Steven E. Martin, Lisa C. Colvin, Drew E. Gonzalez, Matthew J. Mcallister

International Journal of Exercise Science: Conference Proceedings

Firefighters (FF) and law enforcement officers (LEO) have heightened cardiovascular disease (CVD) risk due to the stressful nature of their occupations. Data suggest that 45% of on-duty FF fatalities are related to CVD, while LEO have a 1.7 times higher CVD prevalence compared to the general public. To our knowledge, studies comparing FF to LEO, in terms of CVD risk factors, have not been published. This information is necessary to better understand differences in occupational disease risk, as well as to help bridge the gap between stress and CVD markers. PURPOSE: To compare CVD risk biomarkers, fitness, and body …

Dna Hypomethylation Ameliorates Erosive Inflammatory Arthritis By Modulating Interferon Regulatory Factor-8, Gaurav Swarnkar, Nicholas P Semenkovich, Manoj Arra, Dorothy K Mims, Syeda Kanwal Naqvi, Timothy Peterson, Gabriel Mbalaviele, Chia-Lung Wu, Yousef Abu-Amer

2020-Current year OA Pubs

Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the …

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity And Inflammation In Myeloproliferative Neoplasms, Fan He, Angelo Ba Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel Ac Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, Layow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D'Alessandro, Jorge Di Paola, Stephen T. Oh

2020-Current year OA Pubs

Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and …

Impaired Neutrophil Extracellular Trap-Forming Capacity Contributes To Susceptibility To Chronic Vaginitis In A Mouse Model Of Vulvovaginal Candidiasis, Junko Yano, Paul L. Fidel

School of Dentistry Faculty Publications

Vulvovaginal candidiasis (VVC), caused by is characterized by aberrant inflammation by polymorphonuclear neutrophils (PMNs) in the vaginal lumen. Data from the established murine model shows that despite potent antifungal properties, PMNs fail to clear due to local heparan sulfate that inhibits the interaction between PMNs and , resulting in chronic vaginal immunopathology. To understand the role of neutrophil extracellular traps (NETs) in defense against at the vaginal mucosa, we investigated the NET-forming capacity of PMNs in chronic VVC-susceptible (CVVC-S/C3H) and -resistant (CVVC-R/CD-1) mouse strains. Immunofluorescence revealed the formation of NETs (release of DNA with PMN-derived antimicrobial proteins) in PMN cocultures …

A New Perspective On Intervertebral Disc Calcification-From Bench To Bedside, Emanuel Novais, Rajkishen Narayanan, Jose Canseco, Koen Van De Wetering, Christopher Kepler, Alan Hilibrand, Alex Vaccaro, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular …

Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …

Ketosis Prevents Abdominal Aortic Aneurysm Rupture Through C-C Chemokine Receptor Type 2 Downregulation And Enhanced Extracellular Matrix Balance, Sergio Sastriques-Dunlop, Santiago Elizondo-Benedetto, Batool Arif, Rodrigo Meade, Mohamed S Zaghloul, Hannah Luehmann, Gyu S Heo, Sean J English, Yongjian Liu, Mohamed A Zayed

2020-Current year OA Pubs

Abdominal aortic aneurysms (AAAs) are prevalent with aging, and AAA rupture is associated with increased mortality. There is currently no effective medical therapy to prevent AAA rupture. The monocyte chemoattractant protein (MCP-1)/C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA inflammation, matrix-metalloproteinase (MMP) production, and extracellular matrix (ECM) stability. We therefore hypothesized that a diet intervention that can modulate CCR2 axis may therapeutically impact AAA risk of rupture. Since ketone bodies (KBs) can trigger repair mechanisms in response to inflammation, we evaluated whether systemic ketosis in vivo could reduce CCR2 and AAA progression. Male Sprague-Dawley rats underwent surgical AAA …

Sensory Neurons Promote Immune Homeostasis In The Lung, Masato Tamari, Aaron M Ver Heul, Masato Hoshi, Anna M Trier, Ting-Lin Yang, Sanjay Jain, Steven Van Dyken, Et Al.

2020-Current year OA Pubs

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1