Medical Pathology Commons^™

Exploring The Mechanistic Interplay Between Chronic Inflammation And Gastrointestinal Cancer In The Gut Microbiome: A Review, Hanan Mohamed Abd Elmoneim

Saudi Toxicology Journal

There are complex and heterogeneous immunological milieus of the gastrointestinal system, so there is a high mortality rate from malignancies affecting the gastrointestinal system. The pathophysiology of cancer has long been thought to be significantly influenced by inflammation. However, several of the mechanisms underlying its tumor-promoting activities have only lately been discovered. Both beneficial and harmful microorganisms play a crucial role in controlling the host immune system and, eventually, inflammation. Furthermore, bacteria may also influence how a tumor develops through different mechanisms, including long-term inflammation activation, changes to the tumor microenvironment, and genotoxic response induction. A significant percentage of cancers …

Effect Of Vitamin K Supplementation On Insulin Resistance: A Review, Samantha Mccord, Rebecca Willier, Kaitlyn Kirby, Kaylin Mahoney, Lance Dillon, Rileigh Rahrig, Brianna Lu, Joshua Honaker, Emily Eddy

Pharmacy and Wellness Review

Insulin resistance is one of the pathological hallmarks that leads to the development of type II diabetes mellitus (T2DM). Around 40% of people aged 18 to 44 living in the United States have insulin resistance. Recent research, coupled with a better understanding of how vitamin K functions in the body, suggests that this vitamin could potentially help reduce insulin resistance. Vitamin K is not included in the American Diabetes Association (ADA) guidelines for the treatment of insulin resistance, but it has been shown to have some benefits in patients with T2DM. It may also serve as a treatment option for …

Alpha Synuclein And Inflammaging, Geneviève L. Putnam, Robert W. Maitta

Faculty Scholarship

The α-synuclein protein is an established molecule in Lewy body pathology, especially Parkinson's disease (PD). While the pathological role of α-synuclein (α-syn) in PD has been well described, novel evidence may suggest that α-syn interacts with inflammasomes in response to aging. As age is an inevitable physiological state and is also considered the greatest risk factor for PD, this calls for investigation into how α-syn, aging, and PD could be linked. There is a growing amount of data regarding α-syn normal function in the body that includes involvement in cellular transport such as protein complexes assembly, vesicular trafficking, neurotransmitter release, …

Tailoring T Fh Profiles Enhances Antibody Persistence To A Clade C Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Chase E. Hawes, Sonny R. Elizaldi, Justin C. Smith, Dhivyaa Rajasundaram, Gabriel Kristian Pedersen, Xiaoying Shen, La Tonya D. Williams, Georgia D. Tomaras, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer

School of Medicine Faculty Publications

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Disease Footprints: Understanding Basic Pathophysiology, Jeff Vasiloff, Md, Mph

OHIO Open Faculty Textbooks

Basic pathophysiology explained by Jeffrey Vasiloff, MD, MPH, Associate Clinical Professor, PA Program; Adjunct Professor, PT Program, College of Health Sciences and Professions, Ohio University Dublin Medical Campus; Physician Consultant: Ohio Association of Physician Assistants; Physician Volunteer: Franklin County & Columbus Medical Reserve Corps; Board Certification: Internal Medicine & Diabetes and Endocrinology.

The Role Of Micrornas In Cellular Senescence, Inflammation, And Cancer Induced By Childhood Obesity, Sarah S. Siddiqi

Honors Undergraduate Theses

Childhood obesity has escalated into a major public health crisis with serious implications for long-term health. As obesity rates among children continue to rise globally, it is crucial to understand its effects on cellular aging and inflammation—key processes that underpin many metabolic diseases. Obesity not only directly contributes to various metabolic disorders but also disrupts fundamental cellular mechanisms, accelerating aging and fostering systemic inflammation. By examining the impact of obesity on cellular aging and chronic inflammation, as well as the regulatory role of microRNAs (miRNAs) in these pathways, we have been able to identify critical biomarkers and molecular mechanisms involved …

Pdgfra And B Copositive Fibroblasts Drive Fibrosis In Mouse Salivary Glands Through Tgfβ Signaling, Renae Williams Atkinson

Electronic Theses & Dissertations (2024 - present)

Fibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways …

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …

Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford

Faculty, Staff and Student Publications

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in …

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …

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 …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …

Characterization Of The Role Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) Using A Genetic Knockout Mouse Model, Maaged A. Akiel

Theses and Dissertations

In the US, the incidence and mortality rates of hepatocellular carcinoma (HCC) are alarmingly increasing since no effective therapy is available for the advanced disease. Activation of IGF signaling is a major oncogenic event in diverse cancers, including HCC. Insulin-like growth factor binding protein-7 (IGFBP7) inhibits IGF signaling by binding to IGF-1 receptor (IGF-1R) and functions as a potential tumor suppressor for hepatocellular carcinoma (HCC). IGFBP7 abrogates tumors by inducing cancer-specific senescence and apoptosis and inhibiting angiogenesis. We now document that Igfbp7 knockout (Igfbp7-/- ) mouse shows constitutive activation of IGF signaling, presents with pro-inflammatory and immunosuppressive microenvironment, and develops …

Gout, Lorrie Listebarger

Nursing Student Class Projects (Formerly MSN)

Gout is a syndrome caused by an inflammatory response creating an over production of uric acid increasing uric acid levels in the blood and body fluids. Gout is defined as a disorder resulting from tissue deposition of MSU crystals (in joints, bursae, bone, and certain other soft tissues, such as ligaments, tendons and occasionally, skin) and/or crystallization of uric acid within the renal collecting system (tubules and renal pelvis) that typically occurs in acid urine” (Terkeltaub & Edwards, 2013, p. 20). Gout is among the oldest diseases affecting approximately 3.9% of adults in America (Terkeltaub & Edwards, 2013, p. xv). …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

Phenotypic Alterations In Type Ii Alveolar Epithelial Cells In Cd4+ T Cell Mediated Lung Inflammation, Marcus Gereke, Lothar Gröbe, Silvia Prettin, Michael Kasper, Stefanie Deppenmeier, Achim D. Gruber, Richard I. Enelow, Jan Buer, Dunja Bruder

Dartmouth Scholarship

Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4+ T cell recognition of alveolar antigen. This model …