Medical Sciences Commons^™

Exploratory Evaluation Of Mir-146, Inflammatory Biomarkers, And Subjective Cognitive Symptoms In Chronic Migraine ​, Hale Gök Dağidir, Duygu Bandirmali, Merve Hi̇lal Ceren Akgör, Doğa Vuralli, Meltem Yalinay, Güvem Gümüş Akay, Hayrunni̇sa Bolay

Turkish Journal of Medical Sciences

Background/aim: Chronic migraine (CM) is a disabling neurological disorder associated with substantial impairment of quality of life. Increasing evidence suggests that inflammatory and epigenetic mechanisms may contribute to migraine pathophysiology. miR- 146, a microRNA involved in the TLR-4/NFkb pathway, is known to regulate proinflammatory signaling, whereas HMGB1 activates inflammatory pathways through TLR2 and TLR4 receptors. IL-17 is another proinflammatory cytokine implicated in both inflammation and cognitive processes. In this research, our aim was to investigate the relationship between serum HMGB1, IL-17, and miR-146 levels and migraine-related subjective cognitive symptoms in patients with CM.

Materials and methods: Serum samples were collected …

Erratum To “Effects Of Colchicine On Sah-Induced Vascular Damage In An Experimental Subarachnoid Hemorrhage Model’’ [Turkish Journal Of Medical Sciences 56 (2) 2026 597-607] ​, Emi̇ne Demi̇r, Cumaali̇ Demi̇rtaş, Cansu Sönmez, Eray Meti̇n Güler, Sarper Kocaoğlu, Hakan Beyaztaş, Eyüp Çeti̇n

Turkish Journal of Medical Sciences

The original article can be accessed at https://doi.org/10.55730/1300-0144.6192.

Background/aim: Subarachnoid haemorrhage (SAH) is a severe cerebrovascular condition with high morbidity and mortality. Inflammation and oxidative stress are key factors in its pathophysiology, particularly in secondary vascular injury. This study aimed to evaluate the effects of colchicine on vascular integrity and biochemical markers following SAH in an experimental rat model.

Materials and methods: Eighteen female Sprague-Dawley rats were divided into three groups: Control (no SAH), SAH (induced without treatment), and SAH + Colchicine (1 mg/kg intraperitoneally at 1 h and 24 h). SAH was induced by autologous blood injection into …

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun

The Brown Foundation: Institute of Molecular Medicine

Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, but the role of macrophage-intrinsic extracellular proteolysis in immunometabolic regulation remains unclear. Matrix metalloproteinase-14 (MMP14), a membrane-bound protease, is strongly induced during monocyte-to-macrophage differentiation and further elevated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacological inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, phagocytosis, and inflammatory activation in response to obesity-associated adipose tissue signals. Mechanistically, MMP14 promoted inflammatory programming by increasing endotrophin generation and enhancing TLR4-NFκB signaling. MMP14 also reprogrammed macrophage lipid metabolism by suppressing lipolysis and promoting lipid accumulation, altering metabolic communication with neighboring …

A Systematic Literature Review Of Cvid Reveals Pervasive Detrimental Noninfectious Manifestations, Robert B Lindell, Samir U Sayed, Jose S Campos Duran, Sydney A Sheetz, Apoorva Babu, Montana S Knight, Andrea A Mauracher, Ceire A Hay, Peyton E Conrey, Julie C Fitzgerald, Nadir Yehya, Stephen T Famularo, Teresa Arroyo, Richard Tustin, Hossein Fazelinia, Edward M Behrens, David T Teachey, Lisa R Forbes Satter, Alexandra F Freeman, Jenna Re Bergerson, Steven M Holland, Jennifer W Leiding, Scott L Weiss, Mark W Hall, Deanne M Taylor, Rui Feng, E John Wherry, Nuala J Meyer, Sarah E Henrickson

Faculty, Staff and Students Publications

BACKGROUND

Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear.

METHODS

We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity.

RESULTS

Unsupervised clustering of plasma cytokines identified 3 immunologic subgroups, including a high-severity group (“Group C”) characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a …

Relationships Between The Corpus Callosum Index And Current Blood Parameters And Temporal Changes In These Parameters In Patients With Multiple Sclerosis, Oruç Şahin, Muzaffer Güneş

Neurosciences

Objectives: This study aimed to investigate changes in blood parameters and examine the relationships among the corpus callosum index (CCI), plaque characteristics, and blood parameters in multiple sclerosis (MS) patients. In MS, the CCI is associated with brain atrophy and disease progression.

Methods: In this retrospective, cross-sectional study, demographic data from 103 MS patients (38 males), along with blood parameters obtained five years earlier and current values, were analyzed in relation to magnetic resonance imaging (MRI) findings. The CCI calculated from MRI scans was assessed in relation to plaque distribution and number. Statistical analyses included paired sample t tests, Wilcoxon …

Interleukin-6 Inhibition For Patients With Acute Myocardial Infarction: A Systematic Review And Meta-Analysis, Mohammed Y. Alasmary, Mohammed J. Almalki, Faisal H. Almalki, Waleed D. Khubzan, Mohammed H. Rajab, Mohammed S. Almalki, Hussam A. Almalki, Omar M. Alsuwat, Hussam M. Alghannami

Saudi Medical Journal

Objective: To explore the outcomes associated with interleukin-6 (IL-6) pathway blockade, using tocilizumab, in patients with ST-elevation myocardial infarction (STEMI) and non (NSTEMI). Acute myocardial infarction (AMI) denotes myocardial necrosis due to ischemia and presents in distinct electrocardiographic phenotypes. Inflammation driven by IL-6 contributes to ischemia-reperfusion injury, with tocilizumab showing promise in reducing myocardial damage and improving outcomes.

Methods: This work followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Framework and was registered in international prospective register of systematic reviews (PROSPERO). Relevant studies were identified through structured searches of PubMed, MEDLINE, the Cochrane Library, and Google Scholar up …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

A Critically Appraised Topic: Effectiveness Of Hydrogen-Rich Water Therapies In Reducing Inflammation, Bill Craig, Dawn Hammerschmidt, Jay Albrecht

Dissertations, Theses, and Projects

Inflammation is an important part of healing, but prolonged inflammation or inflammatory disease can cause excess pain and tissue damage. Hydrogen-rich water therapies have shown to have positive effects on this wide variety of conditions and may have a role in future therapeutic intervention for inflammatory conditions and acute injury care. Hydrogen is a commonly known element that has recently been the subject of scientific studies to analyze its beneficial properties when used as a therapeutic intervention. Hydrogen is physically the smallest element on the periodic table, and when two hydrogen atoms combine to form H2, it is known as …

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

Alterations In Gut Microbiota And Their Association With Intestinal Mucosal Injury In Children With Febrile Seizures, Lin Yang, Shuan Yin, Wenchao Zou

Neurosciences

Objective: To explore the correlation between diversity of the gut microbiota and key markers of inflammation and intestinal mucosal injury in pediatric febrile seizures (FS).

Methods: This study compared 15 FS children (FS group) and 15 healthy individuals (normal control group). The participants underwent 16S rDNA sequencing to analyze gut microbiota profiles. ELISA was employed to measure peripheral blood concentrations of the pro-inflammatory cytokines TNF-α and IL-6, as well as intestinal mucosal injury indicators such as endotoxin (BT), D-lactate (D-Lac), and diamine oxidase (DAO). Analysis assessed the correlation between gut microbiota composition, inflammatory factors, and indicators of intestinal mucosal damage …

Pharmacologic Interventions To Reduce Cardiopulmonary Bypass Induced Inflammation In Cardiac Surgery: A Scoping Review, Wyatt Anderson

Student Works

ABSTRACT

1. Structured summary

Background

Cardiopulmonary bypass (CPB) is essential in cardiac surgery but can trigger a systemic inflammatory response that contributes to postoperative complications. The scoping review conducted has a purpose to map the existing literature on pharmacologic interventions to mitigate CPB related inflammation. While several interventions demonstrated potential anti-inflammatory effects, findings were inconsistent, and no standardized pharmacologic approach is currently agreed upon.

Methods

This scoping review followed PRISMA-ScR guidelines.Both PubMed, and CINAHL were screened for studies published between 2000 and 2024 that evaluated pharmacologic interventions aimed at reducing CPB related inflammation. After screening and duplicate removal, 10 studies met …

Stress-Induced Il-6 Response Patterns Amplify The Link Between Daily Negative Affect And Later Depressive Symptoms During Bereavement, E Lydia Wu-Chung, Daniel L Argueta, Robert Suchting, Ryan L Brown, Michelle A Chen, Angie S Leroy, Kyle W Murdock, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Depressive symptoms frequently follow exposure to major life stressors, such as spousal bereavement. However, long-term mental well-being varies considerably. Previously, daily negative affect significantly predicted future depressive symptoms. Higher daily negative affect may signify worse long-term mental health for individuals who also show enhanced inflammatory responses to acute stress, as heightened physiological reactivity to acute stress has been linked with increased susceptibility to depression. Among widow(er)s, we examined whether stress-induced inflammatory responses altered the magnitude of the association between daily negative affect and future depressive symptoms. In exploratory analyses, we examined whether these patterns differed between bereaved and nonbereaved adults. …

Inflammation- And Resolution-Programmed Myeloid Circuits Govern Therapeutic Resistance In Epithelial And Mesenchymal Triple-Negative Breast Cancer, Liqun Yu, Charlotte Rivas, Fengshuo Liu, Yichao Shen, Ling Wu, Zhan Xu, Yunfeng Ding, Xiaoxin Hao, Weijie Zhang, Hilda L Chan, Jun Liu, Bo Wei, Yang Gao, Luis Becerra-Dominguez, Yi-Hsuan Wu, Siyue Wang, Tobie D Lee, Xuan Li, Xiang Chen, David G Edwards, Xiang H-F Zhang

Faculty, Staff and Students Publications

Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes - proinflammatory and proresolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas proresolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemoimmunotherapy, mesenchymal-like tumors expanded proresolution macrophages through phagocytosis/efferocytosis, ω-3 fatty acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory …

Effects Of Colchicine On Sah-Induced Vascular Damage In An Experimental Subarachnoid Hemorrhage Model ​, Emi̇ne Demi̇r, Cumaali̇ Demi̇rtaş, Cansu Sönmez, Eray Meti̇n Güler, Sarper Kocaoğlu, Hakan Beyaztaş, Eyüp Çeti̇n

Turkish Journal of Medical Sciences

Background/aim: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular condition associated with high morbidity and mortality. Inflammation and oxidative stress play critical roles in its pathophysiology, especially in the development of secondary vascular damage. This study aimed to evaluate the protective effects of colchicine on vascular integrity and biochemical markers following SAH in an experimental rat model.

Materials and methods: Eighteen female Sprague Dawley rats were randomly divided into 3 groups: Control (no SAH), SAH (induced without treatment), and SAH + colchicine (received intraperitoneal colchicine at a dose of 1 mg/kg). SAH was induced by injecting autologous blood into the cisterna …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

The Impact Of Estrogen Replacement During Perimenopause On Lung Function And Airway Inflammation In The Vcd Mouse Model, William P Pederson, Laurie Michelle Ellerman, Riley D Hellinger, Joselyn Joanna Rojas Quintero, Francesca Polverino, John P Konhilas, Julie G Ledford

Faculty, Staff and Students Publications

Background:

Menopause associated asthma impacts a subset of women and is less responsive to current treatments. Mechanisms driving this late onset asthma are unknown. We recently developed a mouse model of menopause associated asthma using a combination of 4-Vinylcyclohexene Diepoxide (VCD) and House Dust Mite (HDM) exposures. The goal of this study was to determine how hormone replacement therapy during perimenopause impacts lung function and inflammation.

Methods:

The experimental groups included menopausal mice (VCD) with and without exposure to HDM (to model allergic airways disease) and menopausal mice with and without hormone replacement therapy (HRT; via estrogen pellet implantation). Lung …

Telomerase Knockout In Myeloid Cells Predisposes Mice To Foam Cell Formation, Dyslipidemia, Lung Fibrosis, And Cardiac Dysfunction, Zhanguo Gao, Yongmei Yu, David Wiggins, Eva M Sevick-Muraca, Mikhail G Kolonin

The Brown Foundation: Institute of Molecular Medicine

Aging-associated changes in myeloid cells are incompletely understood. One of the culprits of aging is the downregulation of the Tert gene coding for the catalytic subunit of telomerase. Studies of mouse models with Tert knockout (KO) in specific cells have revealed the importance of the telomere-independent noncanonical function of TERT in supporting mitochondrial metabolism and protection from cell senescence. To investigate the role of TERT in myeloid cells (MCs), we analyzed mice with Tert KO in the LysM+ lineage, indelibly labeled with membrane green fluorescent protein (mG). Macrophage numbers and properties in various organs were compared. Changes in the vasculature, …

Filifactor Alocis Disrupts Efferocytosis To Sustain Inflammation In Periodontitis, Ella Dye, Silvia Uriarte, Ruth Idowu

The Cardinal Edge

Background: Filifactor alocis is a Gram-positive, obligate anaerobe that has emerged as a diagnostic marker of periodontitis. Neutrophils and macrophages are key players in oral immune homeostasis. Neutrophils are short-lived cells and constitutively undergo apoptosis. This apoptotic program can be accelerated or delayed by bacterial interactions. Macrophages clear apoptotic neutrophils via “efferocytosis,” a crucial mechanism for resolving inflammation and preventing tissue damage. The efferocytic process downregulates the expression and release of proinflammatory cytokines such as interleukin (IL)-6 and IL-23 while promoting anti-inflammatory responses. Our previous findings demonstrated that F. alocis delays neutrophil apoptosis, with fewer apoptotic cells observed after 18 …

Inverse Associations Of Serum Total Omega-6 Polyunsaturated Fatty Acids And Linoleic Acid With Biomarkers Of Inflammation: A Cross-Sectional Analysis, Kevin C Maki, Xiwei Chen, Meredith L Wilcox, Carol F Kirkpatrick, Liana L Guarneiri, Orsolya M Palacios, Erika T Beidelman, Anna Lm Macagno, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Observational evidence supports associations between higher consumption of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with reduced risks for cardiometabolic diseases. However, some have hypothesized that higher n-6 PUFA intake may be proinflammatory.

Objectives: The purpose of this cross-sectional analysis using baseline data from the Aegis cohort was to examine associations of serum total n-6 PUFA and linoleic acid concentrations with biomarkers of inflammation.

Methods: Serum concentrations of high-sensitivity C-reactive protein (hs-CRP), glycoprotein acetyls, serum amyloid A (SAA), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were assessed as biomarkers of inflammation. Univariate Pearson correlation coefficients …

Prenatal Stress Induces Changes In Behavior, Hpa Axis, Inflammation, And Oxidative Stress In Adult Rats Offspring, Jorge M Aguiar-Geraldo, Jefté Peper-Nascimento, José Henrique Cararo, Taise Possamai-Della, Alexandra I Zugno, Anilkumar Pillai, João Quevedo, Samira S Valvassori

Faculty, Staff and Student Publications

Prenatal stress is related to the development of psychiatric disorders involving inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the aim of the present study was to evaluate the effects of prenatal stress on behavior, inflammation, oxidative stress, and the HPA-axis in the dams and their offspring treated with lithium. Thirteen pregnant Wistar rats were exposed to a prenatal chronic unpredictable stress protocol from the 14th day of gestation until birth. At the 60th postnatal day (PND), a treatment protocol was carried out in the offspring with lithium (intraperitoneally - 47.5 mg/kg) or saline for seven days (twice a day). …

Multimodal Spatial-Omics Reveal Co-Evolution Of Alveolar Progenitors And Proinflammatory Niches In Progression Of Lung Precursor Lesions, Fuduan Peng, Ansam Sinjab, Yibo Dai, Warapen Treekitkarnmongkol, Sujuan Yang, Lorena I Gomez Bolanos, Tieling Zhou, Minyue Chen, Alejandra G Serrano, Avantika Krishna, Nastaran Karimi, Manvi Sharma, Akshay Basi, Guangsheng Pei, Jianlong Liao, Yunhe Liu, Jiping Feng, Zahraa Rahal, Yang Liu, Jiahui Jiang, Kai Yu, Tala Noun, Yuejiang Liu, Khaja Khan, Kyung Serk Cho, Jichao Chen, Luisa M Solis, Sarah Mazzilli, Steven Dubinett, Tina Cascone, Avrum E Spira, Stephen Swisher, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Tomoo Itoh, Takashi Yao, Kenji Suzuki, Neda Kalhor, Ignacio I Wistuba, Mingyao Li, Seyed Javad Moghaddam, Junya Fujimoto, Jared Burks, Jeffrey Myers, Kadir Akdemir, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are …

Multimodal Spatial-Omics Reveal Co-Evolution Of Alveolar Progenitors And Proinflammatory Niches In Progression Of Lung Precursor Lesions, Fuduan Peng, Ansam Sinjab, Yibo Dai, Warapen Treekitkarnmongkol, Sujuan Yang, Lorena I Gomez Bolanos, Tieling Zhou, Minyue Chen, Alejandra G Serrano, Avantika Krishna, Nastaran Karimi, Manvi Sharma, Akshay Basi, Guangsheng Pei, Jianlong Liao, Yunhe Liu, Jiping Feng, Zahraa Rahal, Yang Liu, Jiahui Jiang, Kai Yu, Tala Noun, Yuejiang Liu, Khaja Khan, Kyung Serk Cho, Jichao Chen, Luisa M Solis, Sarah Mazzilli, Steven Dubinett, Tina Cascone, Avrum E Spira, Stephen Swisher, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Tomoo Itoh, Takashi Yao, Kenji Suzuki, Neda Kalhor, Ignacio I Wistuba, Mingyao Li, Seyed Javad Moghaddam, Junya Fujimoto, Jared Burks, Jeffrey Myers, Kadir Akdemir, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are …

The Hidden Link Between Endometriosis And Obesity: A State-Of-The-Art Review, Shefali N Desai, Christina C Reed, Yamely Mendez, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Endometriosis remains an under-researched disease with a wide range of symptoms. Endometriosis reduces a woman's quality of life and professional productivity, yet its exact causes, risk factors, and treatment have yet to be elucidated. Body mass index and endometriosis have been observed to be inversely related; however, this relationship may only be a correlation rather than a causation. Obesity may play a role in the inflammation and cell proliferation associated with endometriosis through the complex signaling pathways of adipokines. A literature review was done on endometriosis and obesity to gain insight and synthesize knowledge about opportunities to improve endometriosis care, …

Epigenome-Wide Association Study Meta-Analysis Of Bmi In African Americans, Kendra Ferrier, Mariaelisa Graff, Iain R Konigsberg, Maggie Stanislawski, Heather M Highland, Laura M Raffield, April P Carson, Eric Boerwinkle, Jill M Norris, Chris R Gignoux, Audrey E Hendricks, Sridharan Raghavan, Kari E North, Kristin L Young, Anne E Justice, Matthew A Allison, Mathew J Budoff, Silva Kasela, François Aguet, Joshua J Joseph, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Ethan M Lange, Leslie A Lange

Faculty, Staff and Student Publications

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and …

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: The East Palestine, Ohio, train derailment on February 3rd, 2023, resulted in the exposure of residents and the surrounding area to numerous hazardous chemicals, which included known acute irritants and human carcinogens. Despite evacuation and cleanup, both residents and responders reported high occurrences of symptoms associated with exposure in the months following, such as eye, skin, and respiratory irritation, headaches, and fatigue. The long-term health consequences for residents remain uncertain.

Objective: To assess the potential for immune perturbations resulting from the exposure, we performed a broad investigation of circulating immune cells and mediators from residents of East Palestine, OH, …

Sex Differences In Allergic Asthma Responses Of Mice Prenatally Exposed To Wood Smoke, Adelynne Walley

Undergraduate Theses, Professional Papers, and Capstone Artifacts

No abstract provided.

Maesa Ramentacea Leaf Extract Protects Against Gentamicin-Induced Nephrotoxicity In Wistar Rats By Modulating Renal Oxidative Stress, Inflammation And Apoptosis, Fahmida Akter, Md Shafiqul Islam Sovon, Baizid Hossain, Md Ariful Islam, Subrato Das, Anik Biswas, Md Sohorab Uddin, Md Mahmudul Hasan

Faculty Publications

Background: Gentamicin-induced nephrotoxicity continues to be a significant clinical concern, while effective and safe protective options remain limited. The nephroprotective potential of Maesa ramentacea has not yet been explored. To address this gap, the present study investigated the ethanolic leaf extract of M. ramentacea (MR-LEE) for its effects on gentamicin-induced kidney injury in Wistar rats. Methods: GC-MS profiling was employed to identify bioactive metabolites. Rats were categorised into five groups: control, gentamicin (100 mg/kg), gentamicin combined with silymarin (100 mg/kg), gentamicin combined with MR-LEE (200 mg/kg) and gentamicin combined with MR-LEE (400 mg/kg). Renal biomarkers, oxidative stress indicators, inflammatory and …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …