Medical Specialties Commons^™

'Educated' Osteoblasts Reduce Osteoclastogenesis In A Bone-Tumor Mimetic Microenvironment., Alexus D. Kolb, Jinlu Dai, Evan T. Keller, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on …

Mithramycin And Analogs For Overcoming Cisplatin Resistance In Ovarian Cancer, David Schweer, J. Robert Mccorkle, Jurgen Rohr, Oleg V. Tsodikov, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Ovarian cancer is a highly deadly malignancy in which recurrence is considered incurable. Resistance to platinum-based chemotherapy bodes a particularly abysmal prognosis, underscoring the need for novel therapeutic agents and strategies. The use of mithramycin, an antineoplastic antibiotic, has been previously limited by its narrow therapeutic window. Recent advances in semisynthetic methods have led to mithramycin analogs with improved pharmacological profiles. Mithramycin inhibits the activity of the transcription factor Sp1, which is closely linked with ovarian tumorigenesis and platinum-resistance. This article summarizes recent clinical developments related to mithramycin and postulates a role for the use of mithramycin, or its analog, …

Abnormal Nutritive Sucking As An Indicator Of Neonatal Brain Injury, Sabrina Shandley, Gilson J. Capilouto, Eleonora Tamilia, David M. Riley, Yvette R. Johnson, Christos Papadelis

Communication Sciences and Disorders Faculty Publications

A term neonate is born with the ability to suck; this neuronal network is already formed and functional by 28 weeks gestational age and continues to evolve into adulthood. Because of the necessity of acquiring nutrition, the complexity of the neuronal network needed to suck, and neuroplasticity in infancy, the skill of sucking has the unique ability to give insight into areas of the brain that may be damaged either during or before birth. Interpretation of the behaviors during sucking shows promise in guiding therapies and how to potentially repair the damage early in life, when neuroplasticity is high. Sucking …

Encephalopathy And Complex Hyperkinesia In A Patient With Severe Acute Respiratory Syndrome Coronavirus-2 Infection, Wenyang Li, Elif Pinar Coskun, Rolando Berger, John T. Slevin, L. Creed Pettigrew

Neurology Faculty Publications

No abstract provided.

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses In Preterm Pigs, William Yakah, David Ramiro-Cortijo, Pratibha Singh, Joanne Brown, Barbara Stoll, Madhulika Kulkarni, Berthe C Oosterloo, Doug Burrin, Krishna Rao Maddipati, Raina N Fichorova, Steven D Freedman, Camilia R Martin

Children’s Nutrition Research Center Staff Publications

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for …

Eus-Guided Pelvic Drainage: A Systematic Review And Meta-Analysis, Banreet Singh Dhindsa, Yassin Naga, Syed Mohsin Saghir, Amaninder Dhaliwal, Daryl Ramai, Chad Cross, Shailender Singh, Ishfaq Bhat, Douglas G. Adler

School of Medicine Faculty Research

Background and Objectives: EUS-guided pelvic abscess drainage (EUS-PAD) is a procedure that utilizes an echoendoscope to visualize an area of interest for needle insertion and placement of a stent, catheter, or both for drainage of the target abscess. The aim of this study was to perform a systematic review and meta-analysis for the safety and efficacy of EUS-PAD. Materials and Methods: We conducted a comprehensive search of several databases and conference proceedings including PubMed, EMBASE, Google Scholar, MEDLINE, SCOPUS, and Web of Science databases (earliest inception to February 2020). The primary outcomes for this study were the technical and clinical …

Genetic Murine Models Of Spinal Development And Degeneration Provide Valuable Insights Into Intervertebral Disc Pathobiology., J. Melrose, S. Tessier, M. V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Disc degeneration and associated back and neck pain elicits a substantial burden on healthcare systems and the individuals affected, necessitating the development of novel therapeutic strategies. This goal can only be achieved by a better understanding of intervertebral disc development, homeostasis and pathogenesis. A number of genetic and in-bred murine models are reviewed to underscore the importance of the mouse as an animal model of choice for the assessment of intervertebral disc pathobiology. Appraisals of the differences between mouse and human musculoskeletal systems and proteoglycan structures are also included. A number of important target pathways and molecules have been identified, …

Colostomy Takedown: Ischemic Complication Following Anorectal Malformation Surgery., Wendy Jo Svetanoff, Justin A. Sobrino Md, Grace S. Mitchell, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Anorectal malformations (ARM) are complex disorders that often require staged reconstructions. We present a case and imaging findings of a child who developed issues following colostomy closure due to segmental colonic ischemia. Case Presentation. A 3-year-old female with Currarino syndrome presented with abdominal distention, blood-flecked stools, and prolonged cecostomy flush time. For her anorectal malformation, a colostomy was initially placed. A new colostomy was created at posterior sagittal anorectoplasty (PSARP) to allow the distal rectum to reach the anus without tension. Differentials for her presenting symptoms included a mislocation of the anus, stenosis at the anoplasty site, stricture …

Functional Cooperativity Between The Trigger Factor Chaperone And The Clpxp Proteolytic Complex, Kamran Rizzolo, Angela Yeou Hsiung Yu, Adedeji Ologbenla, Sa Rang Kim, Haojie Zhu, Koichiro Ishimori, Guillaume Thibault, Elisa Leung, Yi Wen Zhang, Mona Teng, Marta Haniszewski, Noha Miah, Sadhna Phanse, Zoran Minic, Sukyeong Lee, Julio Diaz Caballero, Mohan Babu, Francis T F Tsai, Tomohide Saio, Walid A Houry

Faculty, Staff and Students Publications

A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and the ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of the close proximity of tig, the gene coding for TF, and genes coding for ClpXP, suggesting a functional interaction. The effect of TF on ClpXP-dependent degradation varies based on the nature of substrate. While degradation of some substrates are slowed down or are unaffected by TF, surprisingly, TF increases the degradation rate of a third class of substrates. These include λ phage replication protein λO, master regulator of stationary phase RpoS, and SsrA-tagged proteins. Globally, TF acts to …

A "Blinking" Left Ventricular Assist Device, Maya Guglin, Roopa Rao

The VAD Journal

A 61-year-old male with history of coronary artery disease and end stage ischemic cardiomyopathy underwent a successful implantation of a HeartMate 3 device with an uneventful recovery. However, after 6 months, he complained of increased fatigue, intermittent dizziness, and weakness after minor exertion. The pulsatility index was increased to 8, but the left ventricular assist device (LVAD) was otherwise functioning properly. No major changes in either medications or laboratory results were noted. The patient started getting low flow alarms seven months after the procedure and the dizziness increased. On the controller, a continuously changing (“blinking”) speed was noted (Supplemental Video …

A Case Of Diastematomyelia Presenting With Minimal Neurologic Deficits In A Middle-Aged Patient, Gabriella Mamo, Rishu Batra, Jeffrey Steinig

Transitional Year Resident Research

Diastematomyelia is a rare congenital deformity of the spine in which the spinal cord is split into two hemicords along the sagittal plane. This condition belongs to the group of spinal dysraphisms, is more common in females, and is usually diagnosed prenatally or during childhood; rarely is it diagnosed in adults. We report a male patient in his 50s in which diastematomyelia of the thoracic spine was incidentally encountered after receiving a CT scan of the chest for shortness of breath. Although most patients with this condition are symptomatic, the patient did not display any significant acute neurological complaints at …

Shear Stress Associated With Cardiopulmonary Bypass Induces Expression Of Inflammatory Cytokines And Necroptosis In Monocytes., Lan N. Tu, Lance Hsieh, Masaki Kajimoto, Kevin Charette, Nataliya Kibiryeva, Adriana Forero, Sarah Hampson, Jennifer A. Marshall, James O'Brien, Marta Scatena, Michael A. Portman, Ram Savan, Chris Benner, Alberto Aliseda, Muhammad Nuri, Douglas Bittel, Peter Pastuzsko, Vishal Nigam

Manuscripts, Articles, Book Chapters and Other Papers

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we …

Central Nervous System Intravascular Lymphoma Leading To Rapidly Progressive Dementia, Christie G Turin, Kevin Ting, Anthony Bradshaw, S Richard Dunham, Karen Nunez-Wallace, Shital M Patel, Priti Dangayach, Stephanie Holdener, Weei-Chin Lin

Faculty, Staff and Students Publications

Intravascular lymphoma is an uncommon subtype of B-cell lymphoma with neoplastic cells limited to the lumen of small blood vessels. We report a case of a 52-year-old man who presented with constitutional symptoms and rapidly progressive dementia. He was found to have diffuse leptomeningeal and faint parenchymal enhancement on magnetic resonance imaging and was subsequently diagnosed with intravascular lymphoma following a brain biopsy. He responded remarkably well to systemic and intrathecal chemotherapy. The diagnosis and treatment of intravascular lymphoma have been guided by a few case reports and are largely based on expert opinion.

Epidemiological Characteristics, Ventilator Management, And Clinical Outcome In Patients Receiving Invasive Ventilation In Intensive Care Units From 10 Asian Middle-Income Countries (Provent-Imic): An International, Multicenter, Prospective Study, Luigi Pisani, Anna Geke Algera, Ary Serpa Neto, Areef Ahsan, Abigail Beane, Kaweesak Chittawatanarat, Abul Faiz, Rashan Haniffa, Seyed Mohammadreza Hashemian, Madiha Hashmi

Department of Anaesthesia

Epidemiology, ventilator management, and outcome in patients receiving invasive ventilation in intensive care units (ICUs) in middle-income countries are largely unknown. PRactice of VENTilation in Middle-income Countries is an international multicenter 4-week observational study of invasively ventilated adult patients in 54 ICUs from 10 Asian countries conducted in 2017/18. Study outcomes included major ventilator settings (including tidal volume [V T] and positive end-expiratory pressure [PEEP]); the proportion of patients at risk for acute respiratory distress syndrome (ARDS), according to the lung injury prediction score (LIPS), or with ARDS; the incidence of pulmonary complications; and ICU mortality. In 1,315 patients included, …

Predictive Value Of Blood N-Terminal Pro-Brain Natriuretic Peptide Concentrations For Early Patent Ductus Closure In Very Preterm Infants, Solomiia Potsiurko, Dmytro Dobryanskyy, Lesya Sekretar

Journal of the Saudi Heart Association

Objectives. It has been shown that blood concentrations of NT-proBNP may be useful in identifying preterm infants at risk of hemodynamically significant patent ductus arteriosus and its complications. The aim of the study was to assess predictive value of serum NT-proBNP levels for early ductus arteriosus (DA) closure in very preterm newborns.
Methods. Fifty-two infants weeks’ gestation aged (PDA) diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent planned echocardiographic (daily) …

Right Atrial Volume Index As A Predictor Of Persistent Right Ventricular Dysfunction In Patients With Acute Inferior Myocardial Infarction And Proximal Right Coronary Artery Occlusion Treated With Primary Percutaneous Coronary Intervention, Mohamed Naseem, Sameh Samir

Journal of the Saudi Heart Association

Objectives: Patients with right ventricular (RV) infarctions associated with inferior infarctions have higher rates of adverse events than isolated inferior infarctions. Right atrial volume index (RAVI) has recently been described as a predictor of clinical outcome in patients with chronic systolic heart failure and pulmonary hypertension. The aim of this study is to assess the ability of RAVI to predict the persistent RV dysfunction after acute inferior STEMI due to occlusion of proximal RCA. To the best of our knowledge, this is the first study to investigate the relation between RAVI and persistent RV dysfunction in such group of patients. …

Assessment Of Narcotic Use In Management Of Post-Op Pain After Functional Endoscopic Sinus Surgery., Kurren S. Gill, Chandala Chitguppi, Michelle Haggerty, Tawfiq Khoury, Judd Fastenberg, Gurston Nyquist, Elina Toskala, Marc Rosen, Mindy Rabinowitz

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Objectives: Pain and analgesic requirements after functional endoscopic sinus surgery (FESS) vary widely. This study aims to quantify pain after routine FESS and determine the most commonly used pain management regimen.

Methods: Retrospective chart review of 100 patients who underwent FESS from Oct 2017 to May 2019. Patients prospectively completed a daily pain diary and reported pain levels that were categorized into no pain (0), mild (1-3), moderate (4-7), or severe (8-10). Patients were categorized into narcotics, non-narcotics, combination, or none based on type of analgesic used.

Results: Sixty-nine patients were included. Majority of patients reported either mild (39%) or …

Critical And Ictal Phases In Simulated Eeg Signals On A Small-World Network, Louis R. Nemzer, Gary D. Cravens, Robert M. Worth, Francis Motta, Andon Placzek, Victor Castro, Jennie Q. Lou

Chemistry and Physics Faculty Articles

Healthy brain function is marked by neuronal network dynamics at or near the critical phase, which separates regimes of instability and stasis. A failure to remain at this critical point can lead to neurological disorders such as epilepsy, which is associated with pathological synchronization of neuronal oscillations. Using full Hodgkin-Huxley (HH) simulations on a Small-World Network, we are able to generate synthetic electroencephalogram (EEG) signals with intervals corresponding to seizure (ictal) or non-seizure (interictal) states that can occur based on the hyperexcitability of the artificial neurons and the strength and topology of the synaptic connections between them. These interictal simulations …

Integrated Genetic And Metabolic Landscapes Predict Vulnerabilities Of Temozolomide Resistant Glioblastoma Cells., Selva Rupa Christinal Immanuel, Avinash D Ghanate, Dharmeshkumar S Parmar, Ritu Yadav, Riya Uthup, Venkateswarlu Panchagnula, Anu Raghunathan

Articles, Abstracts, and Reports

Metabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, …

Myc Regulates Ribosome Biogenesis And Mitochondrial Gene Expression Programs Through Its Interaction With Host Cell Factor-1., Tessa M. Popay, Jing Wang, Clare M. Adams, Gregory Caleb Howard, Simona G. Codreanu, Stacy D. Sherrod, John A. Mclean, Lance R. Thomas, Shelly L. Lorey, Yuichi J. Machida, April M. Weissmiller, Christine M. Eischen, Qi Liu, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global …

Partial Inhibition Of Mitochondrial Complex I Ameliorates Alzheimer's Disease Pathology And Cognition In App/Ps1 Female Mice., Andrea Stojakovic, Sergey Trushin, Anthony Sheu, Layla Khalili, Su-Youne Chang, Xing Li, Trace Christensen, Jeffrey L Salisbury, Rachel E Geroux, Benjamin Gateno, Padraig J Flannery, Mrunal Dehankar, Cory C Funk, Jordan Wilkins, Anna Stepanova, Tara O'Hagan, Alexander Galkin, Jarred Nesbitt, Xiujuan Zhu, Utkarsh Tripathi, Slobodan Macura, Tamar Tchkonia, Tamar Pirtskhalava, James L Kirkland, Rachel A Kudgus, Renee A Schoon, Joel M Reid, Yu Yamazaki, Takahisa Kanekiyo, Song Zhang, Emirhan Nemutlu, Petras Dzeja, Adam Jaspersen, Ye In Christopher Kwon, Michael K Lee, Eugenia Trushina

Articles, Abstracts, and Reports

Alzheimer's Disease (AD) is a devastating neurodegenerative disorder without a cure. Here we show that mitochondrial respiratory chain complex I is an important small molecule druggable target in AD. Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 female mice, a translational model of AD. Treatment of symptomatic APP/PS1 mice with complex I inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine maturation, cognitive function and proteostasis, and reduced oxidative stress and inflammation in brain and periphery, ultimately blocking the ongoing neurodegeneration. Therapeutic efficacy in vivo was monitored using translational …

Prognostic Gene Expression Signatures Of Breast Cancer Are Lacking A Sensible Biological Meaning., Kalifa Manjang, Shailesh Tripathi, Olli Yli-Harja, Matthias Dehmer, Galina Glazko, Frank Emmert-Streib

Articles, Abstracts, and Reports

The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large …

An Emergency Department Medical Record Review For Adolescent Intentional Self-Harm Injuries, Anna Hansen, Dessi Slavova, Gena Cooper, Jaryd Zummer, Julia Costich

Emergency Medicine Faculty Publications

BACKGROUND: Non-suicidal self-injury and suicide attempts are increasing problems among American adolescents. This study developed a definition for identifying intentional self-harm (ISH) injuries in emergency department (ED) records coded with International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes. The definition is based on the injury-reporting framework proposed by the Centers for Disease Control and Prevention. The study sought to estimate the definition's positive predictive value (PPV), and the proportion of ISH injuries with intent to die (i.e., suicide attempt).

METHODS: The study definition, based on first-valid external cause-of-injury ICD-10-CM codes X71-X83, T14.91, T36-T65, or T71, captured 207 discharge …

Office Blood Pressure Measurement: A Comprehensive Review, Saulat Siddique, Aamir Hameed Khan, Hunaina Shahab, Yu-Qing Zhang, Jam Chin Tay, Peera Buranakitjaroen, Yuda Turana, Narsingh Verma, Chen-Huan Chen, Hao-Min Cheng

Section of Cardiology

The conventional auscultatory methods for measuring blood pressure have been used to screen, diagnose, and manage hypertension since long. However, these have been found to be prone to errors especially the white coat phenomena which cause falsely high blood pressure readings. The Mercury sphygmomanometer and the Aneroid variety are no longer recommended by WHO for varying reasons. The Oscillometric devices are now recommended with preference for the Automated Office Blood Pressure measurement device which was found to have readings nearest to the Awake Ambulatory Blood Pressure readings. The downside for this device is the cost barrier. The alternative is to …

Multiplex Immunofluorescence To Measure Dynamic Changes In Tumor-Infiltrating Lymphocytes And Pd-L1 In Early-Stage Breast Cancer., Katherine Sanchez, Isaac Kim, Brie Chun, Joanna Pucilowska, William L. Redmond, Walter Urba, Maritza Martel, Yaping Wu, Mary Campbell, Zhaoyu Sun, Gary Grunkemeier, Shu-Ching Chang, Brady Bernard, David B Page

Articles, Abstracts, and Reports

BACKGROUND: The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents.

METHODS: Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine …

Optic Nerve Pit Maculopathy Worsened During Pregnancy: A Case Report, Laura A. Torrado-Cobian, George D. Fivgas

School of Medicine Faculty Publications

Background: To report a case of Optic Disc Pit (ODP) maculopathy exacerbated during pregnancy. Case presentation: A 30-year-old female developed unilateral blurry vision at 10-weeks gestation. Ophthalmic examination revealed left eye reduced visual acuity (VA) with the presence of subretinal fluid temporal to the disc extending to the fovea. On Spectral Domain Optical Coherence Tomography (SD-OCT) subretinal, and intraretinal fluid was confirmed. Laser photocoagulation was tried in an attempt to prevent surgical intervention without success; subsequently, pars plana vitrectomy, internal limiting membrane peel and gas tamponade was performed. Three-weeks later, a full thickness macular hole developed, and repeat surgery was …

Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …

Mitochondria Exert Age-Divergent Effects On Recovery From Spinal Cord Injury, Andrew N. Stewart, Katelyn E. Mcfarlane, Hemendra J. Vekaria, William M. Bailey, Stacey A. Slone, Lauren A. Tranthem, Bei Zhang, Samir P. Patel, Patrick G. Sullivan, John C. Gensel

Physiology Faculty Publications

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue …

Identifying The Mirna Signature Association With Aging-Related Senescence In Glioblastoma., Mutharasu Gnanavel, Akshaya Murugesan, Saravanan Konda Mani, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Articles, Abstracts, and Reports

Glioblastoma (GBM) is the most common malignant brain tumor and its malignant phenotypic characteristics are classified as grade IV tumors. Molecular interactions, such as protein-protein, protein-ncRNA, and protein-peptide interactions are crucial to transfer the signaling communications in cellular signaling pathways. Evidences suggest that signaling pathways of stem cells are also activated, which helps the propagation of GBM. Hence, it is important to identify a common signaling pathway that could be visible from multiple GBM gene expression data. microRNA signaling is considered important in GBM signaling, which needs further validation. We performed a high-throughput analysis using micro array expression profiles from …

Mutyh As An Emerging Predictive Biomarker In Ovarian Cancer, Megan L. Hutchcraft, Holly H. Gallion, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

Approximately 18% of ovarian cancers have an underlying genetic predisposition and many of the genetic alterations have become intervention and therapy targets. Although mutations in MutY homolog (MUTYH) are best known for MUTYH associated polyposis and colorectal cancer, it plays a role in the development of ovarian cancer. In this review, we discuss the function of the MUTYH gene, mutation epidemiology, and its mechanism for carcinogenesis. We additionally examine its emerging role in the development of ovarian cancer and how it may be used as a predictive and targetable biomarker. MUTYH mutations may confer the risk of ovarian …