Pathological Conditions, Signs and Symptoms Commons^™

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, …

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …

Time Is Ticking For Cervical Cancer, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Medicine Faculty Publications

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different …

Cachexia, Chorea, And Pain In Chronic Nonbacterial Osteitis And Inflammatory Bowel Disease: A Case Report, Ladan Agharokh, Katherine Mamola, Andrew G Yu, Annette L Medina, Bhaskar Gurram, Julie Fuller, Jason Y Park, Weina Chen, Veena Rajaram, Matthew R Hammer, Jeff L Waugh

Student and Faculty Publications

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014).

CASE PRESENTATION: A 13-year-old Caucasian boy presented …

Irritable Bowel Syndrome: Proposed Mechanisms Of Pathophysiology And The Underlying Dysregulation Of Brain-Gut Interaction, Hailey Haddix

Senior Honors Theses

Irritable bowel syndrome (IBS) is a disease of the gastrointestinal tract affecting approximately 11-21% of people worldwide (Xiao et al., 2021). This research focuses on the dysregulation of gut homeostasis in IBS and explains how the pathophysiology of the gut is controlled by the bidirectional brain-gut axis. The mechanisms of the brain-gut axis consist of neuro-immune cross talk, neuro-hormone cross talk, microbiome-gut signaling, and the HPA-axis. Each of these contribute to one or more of the possible phenotypes of gut pathophysiology, which could include intestinal permeability, visceral hypersensitivity, and motility disturbance (Xiao et al., 2021). Stress is also an important …