Medicine and Health Sciences Commons^™

Editorial: Ion Channel Trafficking And Cardiac Arrhythmias, Marcel A. G. Van Der Heyden, Brian P. Delisle, Hugues Abriel

Physiology Faculty Publications

No abstract provided.

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …

Comparison Of Serum And Cervical Cytokine Levels Throughout Pregnancy Between Preterm And Term Births, Kristin Ashford, Niraj R. Chavan, Amanda T. Wiggins, Molly Malany Sayre, Andrea Mccubbin, Agatha S. Critchfield, John O'Brien

Nursing Faculty Publications

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births.

Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester).

Results For the CVF …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

The Function Of Erbin, A Scaffold Protein, As A Tumor Suppressor In Colon Cancer, Payton D. Stevens

Theses and Dissertations--Molecular and Cellular Biochemistry

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play important roles in orchestrating cell signaling. Here, we show that Erbin functions as a tumor suppressor in colon cancer. Analysis of Erbin expression in patient specimens reveals that Erbin is downregulated at both mRNA and protein levels in tumor tissues. Functionally, knockdown of Erbin disrupts epithelial cell polarity and increases cell proliferation in 3D culture. In addition, silencing Erbin results in an increase in the amplitude and duration of signaling through Akt and RAS/RAF pathways. Moreover, Erbin-loss induces epithelial-mesenchymal transition (EMT), which coincides with …

Role Of Oxidized Extracellular Vesicles As Early Biomarkers And Inflammatory Mediators In Chemotherapy-Induced Normal Tissue Injury, Chontida Yarana

Theses and Dissertations--Toxicology and Cancer Biology

Significant advances in the efficacy of cancer therapy have been accompanied by an escalation of side effects that result from therapy-induced injury to normal tissues. Patients with high grade cancer or metastasis are often treated with chemotherapy, 50% of which are associated with reactive oxygen species generation and cellular oxidative stress. Heart is the normal tissue most susceptible to chemotherapy-induced oxidative stress and heart disease is the most common leading cause of death in cancer survivors. However, early and sensitive biomarkers to identify heart disease are still lacking. Extracellular vesicles (EVs) are released from cells during oxidative stress and send …