Medicine and Health Sciences Commons^™

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Neutralizing Antibodies Against Ebv Gp42 Show Potent In Vivo Protection And Define Novel Epitopes, Qian Wu, Ling Zhong, Dongmei Wei, Wanlin Zhang, Junping Hong, Yinfeng Kang, Kaiyun Chen, Yang Huang, Qingbing Zheng, Miao Xu, Mu-Sheng Zeng, Yi-Xin Zeng, Ningshao Xia, Qinjian Zhao, Claude Krummenacher, Yixin Chen, Xiao Zhang

Faculty Scholarship for the College of Science & Mathematics

Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and …

Relative Hepatotoxocity, Carcinogenicity, And Toxicogenomics Of Select Dehydropyrrolizidine Alkaloids In Mice, Michael J. Clayton

All Graduate Theses and Dissertations, Fall 2023 to Present

Dehydropyrrolizidine alkaloids are arguably the most important plant derived toxins in terms of impact on human and animal health. Dehydropyrrolizidine alkaloids are a large group of chemically related compounds found in 3% of flowering plants worldwide. Human exposure occurs from ingestion of herbal products including teas supplements or contaminated grain. Animals are exposed through contaminated feed or grazing. There are at least 350 identified toxic PAs, from more than 6,000 plants. The toxins primarily cause liver damage, but some are proven to cause cancer. Indidvidual dehydropyrrolizidine alkaloids vary in their toxic effects. Riddelliine is the only dehydropyrrolizidine alkaloid with extensive …

Novel Treatments For Pxe: Targeting The Systemic And Local Drivers Of Ectopic Calcification, Ida Joely Jacobs, Qiaoli Li

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is a heritable multisystem ectopic calcification disorder. The gene responsible for PXE, ABCC6, encodes ABCC6, a hepatic efflux transporter regulating extracellular inorganic pyrophosphate (PPi), a potent endogenous calcification inhibitor. Recent studies demonstrated that in addition to the deficiency of plasma PPi, the activated DDR/PARP signaling in calcified tissues provides an additional possible mechanism of ectopic calcification in PXE. This study examined the effects of etidronate (ETD), a stable PPi analog, and its combination with minocycline (Mino), a potent inhibitor of DDR/PARP, on ectopic calcification in an Abcc6-/- mouse model of PXE. Abcc6-/- mice, at 4 weeks of …

Heterochronic Serum Proteins, Jeffrey Mason

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Mechanism of ovarian-dependent enhancement of health and longevity in postreproductive female mice

Immune Cells Localize To Sites Of Corneal Erosions In C57bl/6 Mice., Phuong M. Le, Sonali Pal-Ghosh, A. Menko, Mary Ann Stepp

Computational Medicine Center Faculty Papers

Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the …

Voluntary Wheel Running Promotes Resilience To The Behavioral Effects Of Unpredictable Chronic Mild Stress In Male And Female Mice., Elias Elias, Ariel Y Zhang, Abigail G White, Matthew J Pyle, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. …

Effects Of Cannabichromene On Pain And Neuroinflammation In Hiv-1 Tat Transgenic Mice, Sydney Wheeler

Honors Theses

HIV-1 TransActivator of Transcription (Tat) is a vital regulatory protein involved in HIV replication and implicated in development of HIV-associated pain and neurocognitive deficits. Tat is thought to contribute to these pathologies through proinflammatory pathways. Developing mechanisms to curb Tat-mediated inflammation is a key step in improving the quality of life of those living with HIV. Both recreational and medicinal cannabis use is prevalent among many people living with HIV; given this prevalence and the perceived anti-inflammatory benefits of cannabis use, it is important to investigate how chemical constituents of cannabis may impact HIV. In the present study, the effects …

Dynamic Fecal Microbiota Transfer From Mice With Western Diet-Induced Severe Colitis And Colon Tumorigenesis Did Not Exacerbate Colitis Symptoms Or Colon Tumorigenesis In Recipient Mice Fed Either The Ain93g Diet Or The Total Western Diet, Abby D. Benninghoff

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Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter the fecal microbiome composition in mice as com-pared to mice fed a healthy diet, AIN93G (AIN). However, it is unclear whether the gut micro-biome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from host mice fed either AIN or TWD basal diets would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either AIN or TWD directly using a 2x2 factorial experiment …

Effect Of Acute And Repeated Noise Exposure On The Behaviour And Lipid Peroxidation In Brain Tissue Of Male And Female Mice, Gabriella Korsós, Kinga Fodor, Annamária Kiss, Anna Blázovics, Sándor György Fekete

Turkish Journal of Veterinary & Animal Sciences

Despite the increasingly obvious sex differences, male animals are still predominantly used to study stress and related disorders. The aim of this study was to evaluate the effects of repeated noise stress in female and male mice. In the experiment, 12 male and 12 and female SPF/VAF 6-week-old Crl:CD1(lcr) mice were used. After 5 days of acclimatization all animals were placed in the open-field for three consecutive days where each mouse spent 10 min daily without any noise treatment in order to get used to the circumstances of the test. On day 9 to record baseline behaviour the animals were …

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background: Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods: Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Sciences & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …