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Heme Oxygenase-1 Affects Cytochrome P450 Function Through The Formation Of Heteromeric Complexes: Interactions Between Cyp1a2 And Heme Oxygenase-1, J. Patrick Connick, James R. Reed, George F. Cawley, Wayne L. Backes

School of Medicine Faculty Publications

Heme oxygenase 1 (HO-1) and the cytochromes P450 (P450s) are endoplasmic reticulum–bound enzymes that rely on the same protein, NADPH-cytochrome P450 reductase (POR), to provide the electrons necessary for substrate metabolism. Although the HO-1 and P450 systems are interconnected owing to their common electron donor, they generally have been studied separately. As the expressions of both HO-1 and P450s are affected by xenobiotic exposure, changes in HO-1 expression can potentially affect P450 function and, conversely, changes in P450 expression can influence HO-1. The goal of this study was to examine interactions between the P450 and HO-1 systems. Using bioluminescence resonance …

Microbiome For Mars: Surveying Microbiome Connections To Healthcare With Implications For Long-Duration Human Spaceflight, Virtual Workshop, July 13, 2020, Michael Lapelusa, Dorit Donoviel, Sergio E Branzini, Paul E Carlson, Stephanie Culler, Amrita K Cheema, Rima Kaddurah-Daouk, Denise Kelly, Isabelle De Cremoux, Rob Knight, Rosa Krajmalnik-Brown, Stephen L Mayo, Sarkis K Mazmanian, Emeran A Mayer, Joseph F Petrosino, Keith Garrison

Faculty, Staff and Students Publications

The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.

Highlights From Studies Presented At The American Heart Association Scientific Session 2020: Navigating New Roads In Prevention, Aliza Hussain, Mahmoud Al Rifai, Dhruv Mahtta, Jing Liu, Vardhmaan Jain, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF THE REVIEW: This review highlights late-breaking science presented at the American Heart Association Scientific Session 2020 that demonstrated advancements in preventative cardiology and introduced novel treatment approaches for the management of chronic kidney disease, type 2 diabetes, and/or heart failure.

RECENT FINDINGS: The studies reviewed include clinical trials that assessed the use of omecamtiv in the treatment of heart failure with reduced heart failure (GALACTIC-HF); effects of sotagliflozin in patients with diabetes and recent heart failure exacerbation; cardiovascular outcomes with the use of omega-3 carboxylic acids in patients with high vascular risk and atherogenic dyslipidemia (STRENGTH) and omega-3 …

Plasmid-Based Reverse Genetics For Probing Phosphorylation-Dependent Viroplasm Formation In Rotaviruses, Jeanette M Criglar, Sue E Crawford, Mary K Estes

Faculty, Staff and Students Publications

Rotavirus (RV) replication occurs in cytoplasmic compartments, known as viroplasms, that are composed of viral and cellular proteins. Viroplasm formation requires RV nonstructural proteins NSP2 and NSP5 and cellular lipid droplets (LDs); however, the mechanisms required for viroplasm assembly remain largely unknown. We previously identified two conformationally-distinct forms of NSP2 (dNSP2, vNSP2) found in RV-infected cells that interact differentially with hypo- and hyperphosphorylated NSP5, respectively, and indicate a coordinated phosphorylation-dependent mechanism regulating viroplasm assembly. We also reported that phosphorylation of dNSP2 on serine 313 by the cellular kinase CK1α triggers the localization of vNSP2 to sites of viroplasm assembly and …

Myeloperoxidase: A Versatile Mediator Of Endothelial Dysfunction And Therapeutic Target During Cardiovascular Disease, Sophie L. Maiocchi, Jacqueline Ku, Thuan Thai, Enoch Chan, Martin D. Rees, Shane R. Thomas

Education Papers and Journal Articles

Myeloperoxidase (MPO) is a prominent mammalian heme peroxidase and a fundamental component of the innate immune response against microbial pathogens. In recent times, MPO has received considerable attention as a key oxidative enzyme capable of impairing the bioactivity of nitric oxide (NO) and promoting endothelial dysfunction; a clinically relevant event that manifests throughout the development of inflammatory cardiovascular disease. Increasing evidence indicates that during cardiovascular disease, MPO is released intravascularly by activated leukocytes resulting in its transport and sequestration within the vascular endothelium. At this site, MPO catalyzes various oxidative reactions that are capable of promoting vascular inflammation and impairing …

Improved De Novo Alignment Of A Girardia Dorotocephala Ma-C2 (2n = 24) Transcriptome, Labib Rouhana, J F. Ryan, Eugene M. P. Almazan

Biological Sciences Faculty Publications

Improved De novo alignment of a Girardia dorotocephala MA-C2 (2n = 24) transcriptome.

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Role Of Thymidine Phosphorylase In Type 2 Diabetes-Associated High-Risk Of Thrombosis, Adam Belcher

Theses, Dissertations and Capstones

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are the leading causes of death globally that disproportionally affects patients with type 2 diabetes mellitus (T2DM) at a 2-4-fold rate compared to non-diabetic patients. These CVDs result from a blood clot, also known as a thrombus, formed in arteries that can block blood flow resulting in tissue damage and death. Antiplatelet drugs, such as aspirin and clopidogrel, used to prevent thrombosis have been found to be less effective in diabetics and increase the risk of hemorrhagic events. The T2DM epidemic has made it imperative to find therapies that decrease …

Role Of Na/K-Atpase Non-Enzymatic Signaling In Renal Proximal Tubule Sodium Transport, Shreya Tapan Mukherji

Theses, Dissertations and Capstones

The renal proximal tubule (RPT) is the center stage for renal handling of Na+ , a potent determinant of systemic Na+ and volume homeostasis in health and disease. In the RPT, through its classic ion-pumping function, Na + /K+ -ATPase (NKA) generates the Na+ gradient that drives apical Na+ absorption, mostly through Na+ /H+ exchanger (NHE3). In contrast, pharmacological evidence suggests that the activation of the NKA non-enzymatic signaling function, through Src and other signaling partners, triggers a cellular redistribution of NKA and NHE3 that decreases transcellular Na+ flux in cultured RPT cells. However, the physiological relevance of the nonenzymatic …

Na/K-Atpase Alphα1 Regulates Adipogenesis Via Its Conserved Caveolin Binding Motif, Minqi Huang

Theses, Dissertations and Capstones

The Na/K-ATPase (NKA) was identified in 1957 by Dr. Jens C. Skou. It belongs to the P-type ATPase family, which can actively transport ions across cell membranes by using the energy from adenosine triphosphate (ATP) hydrolysis. During the second half of the 20th century, the molecular mechanism of the NKA catalytic cycle was clarified, and the isoform diversity of NKA in different species and organs was identified. The active ion transport through NKA generates cell membrane ion gradients and the electric potential. Hence, the enzymatic function of NKA is critical for cell viability as well as multiple physiological processes including …

Potential Counter Regulatory Effects Of A Gut Microbiota Metabolite In Alleviating Down-Regulation Krüppel-Like Factor 4 In Intestinal Inflammation, Ylva Forslund

Theses, Dissertations and Capstones

Inflammatory bowel disease (IBD) is a medical condition characterized by chronic inflammation of the intestinal epithelium. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is vital for maintaining intestinal epithelial homeostasis. KLF4 promotes differentiation of goblet cells that generate the protective mucus layer. Reduced goblet cell number and defective mucus layer are associated with IBD. Shortchain fatty acids (SCFA) are known to play an important role in the maintenance of a strong and healthy intestinal epithelial layer and also in goblet cell differentiation. However, whether the positive effects of SCFAs on goblet cells are mediated, at least partly, via …

The Epigenetic Effects Of Omega-3 Fatty Acids In Diffuse Large B-Cell Lymphoma, Tanner Jeffrey Bakhshi

Theses, Dissertations and Capstones

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. It is an aggressive cancer, with 50-70% of patients diagnosed at an advanced stage and 30-50% of patients not cured by chemoimmunotherapy. DLBCL is almost always caused by genetic damage sustained during the germinal center (GC) reaction. The mechanisms that govern the GC reaction bear a striking resemblance to those that drive DLBCL. Genomic studies have shown that some of its most common mutations occur in genes that encode epigenetic modifiers, including the lysine (histone) acetyltransferases CREBBP and p300. These mutations prevent the acetylation of multiple histone residues, …

Fusion, 2021, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

The Evolution And Future Of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, And Oncolytic Bacteria To The Treatment Of Solid Tumors, Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan, Kaitlin M. Dailey

Journal Articles: Pathology and Microbiology

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

Developing A Targeted Ultrasound-Responsive Nanobubble-Based Gene Delivery System For Osteoporosis Treatment, Angela Shar

Honors Undergraduate Theses

The overall goal of this project was to develop, optimize, and test an ultrasound-responsive targeted nanobubble for delivering osteoporosis-related silencing genes such as Cathepsin K small interfering RNA (CTSK siRNA) for osteoporosis treatment. The nanobubbles were synthesized using an in situ sonochemical method. The nanobubble (NB) is composed of a gas core made from perfluorocarbon, stabilized with albumin, encapsulated with CTSK siRNA, and embedded with alendronate (AL) for bone targeting (CTSK siRNA-NB-AL). Following its development, the responsiveness of CTSK siRNA-NB-AL to a therapeutic ultrasound probe was examined. The results of biocompatibility tests with human bone marrow-derived mesenchymal stem cells proved …

Short-Term Impact Of The Covid-19 Pandemic On The Global And Turkish Economy, Ömer Açikgöz, Asli Günay

Turkish Journal of Medical Sciences

Background/aim: The Covid-19 pandemic is one of those rare events that affects everyone on earth and changes our lives. The pandemic, which has killed over four million people worldwide, is putting unprecedented pressure on governments to maintain essential health and social services, as well as keep their economies running, even as the virus threatens people's daily life on every level. Thus, the purpose of this study is to discuss the short-term economic impact of the pandemic by assessing its costs using official economic data for both the world and Turkey. Furthermore, this research highlights possible economic, social, and political pathways …

Nonpharmaceutical Interventions In Turkey And Worldwide During Covid-19 Pandemic, Mustafa Necmi̇ İlhan, Hakan Tüzün, Rahmi̇ Kiliç, Nuran Yildirim

Turkish Journal of Medical Sciences

Nonpharmaceutical interventions (NPIs) are actions apart from getting vaccinated and medications, in order to promote deceleration of the spread of illness among people and communities during pandemic. In this article, we aim to examine NPIs applied in Turkey and worldwide due to the COVID-19 pandemic. Some of the NPIs such as isolation, quarantine, and contact tracing were maintained with updates of the Ministry of Health guidelines in Turkey. Some NPIs including travel and partial or full curfew mobilization restrictions were set in accordance with the various periods by the number of cases. Periods of restrictions at autumn 2021 to summer …

Cerebral Hemodynamic Alterations In Patients With Covid-19, Ali̇ Riza Sonkaya, Bi̇lgi̇n Öztürk, Ömer Karadaş

Turkish Journal of Medical Sciences

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups …

Factors Affecting Mortality In Geriatric Patients Hospitalized With Covid-19, Rabi̇a Bağ Soytaş, Damla Ünal, Pinar Arman, Veysel Suzan, Tuğçe Emi̇roğlu Gedi̇k, Günay Can, Bora Korkmazer, Ridvan Karaali̇, Şermi̇n Börekçi̇, Mert Ahmet Kuşkucu, Hakan Yavuzer, Ülev Deni̇z Erdi̇nçler, Alper Döventaş

Turkish Journal of Medical Sciences

Background/aim: We aimed to investigate the factors affecting the mortality of patients aged 65 years or older who were hospitalized with the diagnosis of new coronavirus pneumonia (COVID-19). Materials and methods: This is a retrospective study of patients 65 years old or older with COVID-19 who were hospitalized in İstanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospital, between March 11 and May 28, 2020. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records. We used univariate and multivariate logistic regression methods to explore the risk factors for in-hospital death. Results: A total of 218 patients (112 men, 106 women) …

Sural Nerve Harvest For Infants: Integrated With Information Based On Anatomicaldissections, Mustafa Büyükmumcu, Anil Di̇dem Aydin Kabakçi, Duygu Akin Saygin, Mehmet Tuğrul Yilmaz, Muzaffer Şeker

Turkish Journal of Medical Sciences

Background/aim: The aim of the present study was to determine the course and possible variations of the sural nerve with all anatomical details in human fetal cadavers. Materials and methods: This study was performed on 60 fetal cadavers. Formation type and level of the sural nerve was detected. Results: According to trimesters, it was determined that the mean transverse and vertical distance between the lowest point of the LM and the SN varied between 1.1 and 2.9 mm and 1.54 and 3.58 mm, respectively. Type 2 was the most common seen type of sural nerve (35.83%). It was determined that …

Pain During Walking And Ascending Stairs Before Hyaluronic Acid Injection Was Commonin Patients With Knee Osteoarthritis: A Qualitative Study, Ömer Özkan, Nai̇la Babayeva, Şeri̇fe Şeyma Torğutalp, Ömer Serkan Kara, Gürhan Dönmez, Feza Korkusuz

Turkish Journal of Medical Sciences

Background/aim: Knee osteoarthritis (OA) is a common pathology characterized by degeneration of the articular cartilage. The aim of the research was to ask patients how they decided to make the injection, what treatments they received, their complaints prior to and after the injection and how they feel at the moment, and whether they are currently exercising or not. Thus, to demonstrate the patients' outcomes with their own expression. Materials and methods: A total of 92 knee OA patients completed semistructured interviews, which included six open-ended questions. Results: A total of 92 patients (66 female, 26 male) aged between 36 and …

Umbilical Cord Levels Of Macrophage Migration Inhibitory Factor In Neonatal Respiratorydistress Syndrome, Süleyman Bayraktar, Bi̇lge Bayraktar, Ülkan Kiliç

Turkish Journal of Medical Sciences

Background/aim: We aimed to evaluate the association of the umbilical cord macrophage migration inhibitory factor (MIF) with the respiratory distress syndrome (RDS) in preterm infants. Materials and methods: A total of eighty six preterm infants (38 with RDS and 48 without RDS) were involved in the study. ELISA is the technique assaying MIF values. Results: The mean of the infants' gestational ages and birth weights were significantly different (P = 0.0001). There were no significant differences in sex, delivery mode or exposure to antenatal steroid among the groups (P > 0.05). Umbilical cord MIF levels of the infants were not correlated …

Dynamic Thiol/Disulfide Homeostasis As Oxidative Stress Marker In Diabetic Ketoacidosis, Yavuz Otal, Fati̇h Ahmet Kahraman, Fadi̇me Güllü Haydar, Özcan Erel

Turkish Journal of Medical Sciences

Background/aim: The aim of present study was to investigate the dynamic thiol/disulfide homeostasis as oxidative stress marker in diabetic ketoacidosis (DKA). Materials and methods: A total of 77 participants consisting of 32 patients with DKA and 45 healthy volunteers were included in the study. Thiol/disulfide homeostasis (TDH) [total thiol-native thiol/disulfide changes] were measured in both groups (patient group and control group) using a brand new method developed by Erel and Neselioglu. Half of the difference between total thiol and native thiol concentrations gives the amount of disulfide bond. Results: Total thiol, native thiol, and disulfide levels in blood were found …

Achievements Of The Covid-19 Turkey Platform In Vaccine And Drug Development Withan Approach Of "Co-Creation And Succeeding Together", Hasan Mandal

Turkish Journal of Medical Sciences

Mobilizing the research ecosystem for accelerating vaccine and drug development has been an important reality of the pandemic. This article reviews the scientific advances that are attained by the COVID-19 Turkey Platform for vaccine and drug development against the SARS-CoV-2 virus. The platform that is coordinated by the Scientific and Technological Research Council of Turkey is established with a "co-creation and succeeding together" approach, which involves 436 researchers across 49 different institutions working on 17 vaccine and drug development projects in total. Recent advances of the COVID-19 Turkey Platform include the fourth virus-like particle-based vaccine candidate in the world to …

Managing Life During The Pandemic: Communication Strategies, Mental Health, And Theultimate Toll Of The Covid-19, Mehmet Hakan Türkçapar, Yasemi̇n Kahya, Tuğba Çapar Taşkesen, Hati̇ce Işik

Turkish Journal of Medical Sciences

Background/aim: The purpose of this review was to present the ultimate toll of the COVID-19 pandemic by focusing on the communication strategies and mental health. Materials and methods: We unsystematically reviewed the studies published between 2020 and 2021 from databases such as Google Scholar, Web of Science and ScienceDirect. Firstly, "new-normal" life challenges during the pandemic were discussed along with the public risk communication strategies. Later, mental health problems, posttraumatic growth, and protective factors were reviewed. Results: Literature highlighted that individuals mainly experience COVID-19 related fear, anxiety, stress, negative emotions and sleep problems. Furthermore, the rates of clinically significant depression, …

Epidemiology Of Covid-19: What Changed In One Year?, Cemal Bulut, Yasuyuki̇ Kato

Turkish Journal of Medical Sciences

A coronavirus brought the first pandemic attack of this century as a flu virus did a hundred years ago. This greatest pandemic of the century brings us new opportunities to understand and explore the dynamics of a contagious disease. Nearly two years later, we are still collecting the evidence to understand the disease. Some basic epidemiological properties are still urgently needed. Not only the origin of the virus but also Ro value, possible transmission routes, epidemiologic curves, case fatality rates, seasonality, severity and mortality risk factor, effects on the risk groups, differences between countries and so on still require strong …

Multisystem Inflammatory Syndrome In Children, Selda Hançerli̇ Törün, Di̇lek Yilmaz Çi̇ftdoğan, Ateş Kara

Turkish Journal of Medical Sciences

As the COVID-19 pandemic continues, children can be infected with the virus that causes COVID-19. Clinical symptoms of children with COVID from China, where the disease was first reported, generally were less severe than adults. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infection developed fever, abdominal pain, shock, myocardial insufficiency and they needed to be taken care of in intensive care unit. This new disease has been called multisystem inflammatory syndrome in children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multiorgan involvement as a …

Pregnancy And Covid-19: Prevention, Vaccination, Therapy, And Beyond, Di̇lek Şahi̇n, Atakan Tanaçan, Sophia Ne Webster, Özlem Moraloğlu Teki̇n

Turkish Journal of Medical Sciences

: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has alarmed the world since its first emergence. As pregnancy is characterized by significant changes in cardiovascular, respiratory, endocrine, and immunological systems, there are concerns on issues like the course of disease in pregnant women, safety of medications, route of delivery and risk of obstetric complications. The aim of this review is to summarize the current literature in the management of pregnant women during the COVID-19 pandemic. Although more than 90% of pregnant women with COVID-19 recover without serious morbidity, rapid deterioration of disease and higher …

The Radiological Findings Of Covid-19, Alper Karacan, Yakup Ersel Aksoy, Mehmet Hali̇l Öztürk

Turkish Journal of Medical Sciences

Background/aim: Available information on the radiological findings of the 2019 novel coronavirus disease (COVID-19) is constantly updated. Ground glass opacities (GGOs) and consolidation with bilateral and peripheral distribution have been reported as the most common CT findings, but less typical features can also be identified. According to the reported studies, SARS-CoV-2 infection is not limited to the respiratory system, and it can also affect other organs. Renal dysfunction, gastrointestinal complications, liver dysfunction, cardiac manifestations, and neurological abnormalities are among the reported extrapulmonary features. This review aims to provide updated information for radiologists and all clinicians to better understand the radiological …