Medicine and Health Sciences Commons^™

Mir-17* Suppresses Tumorigenicity Of Prostate Cancer By Inhibiting Mitochondrial Antioxidant Enzymes, Yong Xu, Fang Fang, Jiayou Zhang, Sajni Josson, William H. St. Clair, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Aberrant micro RNA (miRNA) expression has been implicated in the pathogenesis of cancer. Recent studies have shown that the miR-17-92 cluster is overexpressed in many types of cancer. The oncogenic function of mature miRNAs encoded by the miR-17-92 cluster has been identified from the 5' arm of six precursors. However, the function of the miRNAs produced from the 3' arm of these precursors remains unknown. The present study demonstrates that miR-17* is able to suppress critical primary mitochondrial antioxidant enzymes, such as manganese superoxide dismutase (MnSOD), glutathione peroxidase-2 (GPX2) and thioredoxin reductase-2 (TrxR2). Transfection of miR-17* into prostate cancer PC-3 …

Conformation Dependent Monoclonal Antibodies Distinguish Different Replicating Strains Or Conformers Of Prefibrillar Aβ Oligomers, Rakez Kayed, Isabel Canto, Leonid Breydo, Suhail Rasool, Tamas Lukacsovich, Jessica Wu, Ricardo Albay, Anna Pensalfini, Stephen Yeung, Elizabeth Head, J. Lawrence Marsh, Charles Glabe

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.

RESULTS: We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological …

Treatment Outcomes From The Tdc: A Look At Smoking Cessation Among Patients With Co-Occurring Disorders, Chizimuzo T.C. Okoli

Chizimuzo T.C. Okoli

Summary of Key Findings •Smoking abstinence at end of program:

–Intent to treat analysis: 32.2%(83/258) –Among program completers: 41.3%(83/201)

•Significant predictors of abstinence : –Having an alcohol, heroin (or other opioid) or marijuana use history was a significant predictor of being less likely to quit smoking when compared to having no history of substance use disorder. –Having a lower CO level at program enrolment was a significant predictor of being more likely to quit –Attending the TDC program for a longer duration was a significant predictor of being more likely to quit.

Adar2-Dependent Rna Editing Of Glur2 Is Involved In Thiamine Deficiency-Induced Alteration Of Calcium Dynamics, Shuchen Lee, Guang Yang, Yue Yong, Ying Liu, Liyun Zhao, Jing Xu, Xiaomin Zhang, Yanjie Wan, Chun Feng, Zhiqin Fan, Yong Liu, Jia Luo, Zun-Ji Ke

Internal Medicine Faculty Publications

BACKGROUND: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons.

RESULTS: TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated …

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro And Pro-Inflammatory Responses In Mouse Experimental Colitis, Erik R.M. Eckhardt, Jassir Witta, Jian Zhong, Razvan Arsenescu, Violeta Arsenescu, Yu Wang, Sarbani Ghoshal, Marcielle C. De Beer, Frederick C. De Beer, Willem J.S. De Villiers

Internal Medicine Faculty Publications

BACKGROUND: Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.

METHODS: Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial …

The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.

METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each …

Dysregulation Of The Mitogen Granulin In Human Cancer Through The Mir-15/107 Microrna Gene Group, Wang-Xia Wang, Natasha Kyprianou, Xiaowei Wang, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Granulin (GRN) is a potent mitogen and growth factor implicated in many human cancers, but its regulation is poorly understood. Recent findings indicate that GRN is regulated strongly by the microRNA miR-107, which functionally overlaps with miR-15, miR-16, and miR-195 due to a common 5′ sequence critical for target specificity. In this study, we queried whether miR-107 and paralogs regulated GRN in human cancers. In cultured cells, anti-argonaute RNA coimmunoprecipitation with downstream microarray analyses indicates that GRN mRNA is directly targeted by numerous miR-15/107 miRNAs. We further tested this association in human tumors. MiR-15 and miR-16 are known to be …

Gender-Specific Profiles Of Tobacco Use Among Non-Institutionalized People With Serious Mental Illness, Joy L. Johnson, Pamela A. Ratner, Leslie A. Malchy, Chizimuzo T.C. Okoli, Ric M. Procyshyn, Joan L. Bottorff, Marlee Groening, Annette Schultz, Marg Osborne

Chizimuzo T.C. Okoli

Background: In many countries, smoking remains the leading preventable cause of death. In North America, reductions in population smoking levels are stabilising and, in recent years, those involved in tobacco control programming have turned their attention to particular segments of society that are at greatest risk for tobacco use. One such group is people with mental illness. A picture of tobacco use patterns among those with mental illness is beginning to emerge; however, there are several unanswered questions. In particular, most studies have been limited to particular in-patient groups. In addition, while it is recognised that men and women differ …

Cyanidin-3-Glucoside Inhibits Ethanol-Induced Invasion Of Breast Cancer Cells Overexpressing Erbb2, Mei Xu, Kimberly A. Bower, Siying Wang, Jacqueline A. Frank, Gang Chen, Min Ding, Shiow Wang, Xianglin Shi, Zunji Ke, Jia Luo

Internal Medicine Faculty Publications

BACKGROUND: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This …

Endothelial Cell Capture Of Heparin-Binding Growth Factors Under Flow, Bing Zhao, Changjiang Zhang, Kimberly Forsten-Williams, Jun Zhang, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Complement Factor H-Related Proteins Cfhr2 And Cfhr5 Represent Novel Ligands For The Infection-Associated Crasp Proteins Of Borrelia Burgdorferi, Corinna Siegel, Teresia Hallström, Christine Skerka, Hannes Eberhardt, Barbara Uzonyi, Tobias Beckhaus, Michael Karas, Reinhard Wallich, Brian Stevenson, Peter F. Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi.

METHODOLOGY/PRINCIPAL FINDINGS: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins …

Compositions And Methods For Inhibiting Drusen Complement Components C3a And C5a For The Treatment Of Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Activated C3 (C3a) and its receptor (C3aR) and activated C5 (C5a) and its receptor (C5aR) have been shown to induce vascular endothelial growth factor (VEGF) expression in vitro and in vivo. Compositions and methods for inhibiting C3a, C3aR, C5a and C5aR for the treatment and/or prevention of neovascular disease are provided. Also provided are Novel therapeutic targets and diagnostic markers for choroidal neovascularization.

Composition And Methods For Treating Yersinia Pestis Infection, Susan C. Straley, Brian S. Murphy, Stanislav Forman, Christine R. Wulff, Robert D. Perry, Tanya Myers-Morales

Microbiology, Immunology and Molecular Genetics Faculty Patents

Compositions and methods for treating a Yersinia pestis (Y. pestis) infection are provided. Compositions and methods of for inducing an immune response in a subject are provided. Composition can include a YadC polypeptide.

Agmatine And Agmatine Analogs In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David R. Worthen

Pharmaceutical Sciences Faculty Patents

Pharmaceutical preparations containing of agmatine, congeners, analogs or derivatives thereof for use in preventing or treating epilepsy, seizures and other electroconvulsive disorders are provided. Embodiments include administering an effective amount of agmatine, an agmatine analog or a pharmaceutically acceptable salt thereof to a human subject in need of treatment or prevention of epilepsy, seizure or other electroconvulsive disorder to treat, reduce, or prevent the disorder in the subject.

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, And Upar Expression Of Prostate Cancer Cells, Kalvin J. Gregory, Bing Zhao, Diane R. Bielenberg, Sami Dridi, Jason Wu, Weihua Jiang, Bin Huang, Steven Pirie-Shepherd, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.

METHODS AND FINDINGS: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry …

The Us Preventive Service Taskforce And The Guide To Clinical Preventive Services., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

The Us Preventive Service Taskforce And The Guide To Clinical Preventive Services., F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Route Of Administration For Illicit Prescription Opioids: A Comparison Of Rural And Urban Drug Users, April M. Young, Jennifer R. Havens, Carl G. Leukefeld

Behavioral Science Faculty Publications

BACKGROUND: Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA) involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use.

METHODS: A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101) and a major metropolitan area (n = 111) in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported …

High-Intensity Mechanical Therapy For Loss Of Knee Extension For Worker's Compensation And Non-Compensation Patients, Amanda L. Dempsey, Thomas P. Branch, Timothy Mills, Robert M. Karsch

Orthopaedic Surgery and Sports Medicine Faculty Publications

BACKGROUND: Knee flexion contractures have been associated with increased pain and a reduced ability to perform activities of daily living. Contractures can be treated either surgically or conservatively, but these treatment options may not be as successful with worker's compensation patients. The purposes of retrospective review were to 1) determine the efficacy of using adjunctive high-intensity stretch (HIS) mechanical therapy to treat flexion contractures, and 2) compare the results between groups of worker's compensation and non-compensation patients.

METHODS: Fifty-six patients (19 women, 37 men, age = 51.5 ± 17.0 years) with flexion contractures were treated with HIS mechanical therapy as …

Update On The Management Of Chronic Obstructive Pulmonary Disease, Andrea K. Maas, David M. Mannino

David M. Mannino

Chronic obstructive pulmonary disease is a highly prevalent, underdiagnosed, and undertreated chronic lung disease. Early and appropriate treatment may help modify the course of the disease with respect to exacerbation timing and frequency, quality of life, and mortality. Steady progress continues to be made in understanding the disease pathogenesis and treatment modalities, and there is some evidence that outcomes are improving.

Community Health Assesments, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Community Health Assesments, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Insulin Degrading Enzyme Assays For Treatment Of Alzheimer's Disease, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Patents

Estrogen has been shown to increase the expression and activity of amyloid peptide inactivating enzymes in the brain. Peptides have been shown to increase the activity of an amyloid peptide inactivating enzyme. Methods of identifying compounds for, and methods of treating patients with, Alzheimer's Disease is disclosed.

Public Health Services And Systems Research: Data For Research, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Public Health Services And Systems Research: Data For Research, F. Douglas Scutchfield Md

F. Douglas Scutchfield MD

No abstract provided.

Rafinesque And Transylvania’S First Botanical Garden, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Five Early American Botanists: Works And Opinions Of Rafinesque, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Educational Innovations: Categories Of Bulletin Board Postings Designed To Increase Awareness Of Contemporary Pharmaceutical Policy Issues, Jacob T. Painter, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

OBJECTIVE: The goal of this project was to categorize and classify bulletin board postings pertaining to pharmaceutical policy from both the professional and lay press.

METHODS: Bulletin board postings were used to supplement in-class discussion to keep students, faculty and staff up-to-date on emerging trends. A bulletin board located in the main classroom area of the College of Pharmacy Building where students would pass by on the way to class and congregate during break periods was used to display articles from various sources concerning topics related to pharmaceutical policy. Information is presented about the primary subject matters addressed …