Internal Medicine Commons^™

A True Bloody Emergency: An Unusual Case Of Thrombotic Thrombocytopenic Purpura, Joshua M. Ninan

Research Symposium

Background: Thrombotic thrombocytopenic purpura (TTP) is a primary thrombotic microangiopathy that is classically characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Although rare with an annual incidence of 3.7 cases per one million adults, it is considered a true hematological emergency due to its fatality rate of almost 100% if appropriate treatment is not initiated immediately. This makes it vitally important to identify and treat patients with TTP, a task that becomes unusually challenging in the absence of the disorder’s other characteristically diagnostic clinical features such as mucosal bleeding, fever, or presence of schistocytes.

Case Presentation: A 30-year-old gentleman with …

Comparison Of Risk Factors Of Mortality During The Two Coronavirus Disease 2019 Waves In Delhi, India, Neena Katoch, Ajay K. Gupta, Rachna Gulati, Ketan Garg, Vikas Kumar

Journal of Medicine in Scientific Research

Objective To determine the risk factors of mortality (in terms of age, sex, and comorbidities) among hospitalized patients in an Indian tertiary care hospital during the first and second waves. Patients and methods A retrospective observational study was conducted, where the patients’ mortality data were collected over two coronavirus disease 2019 (COVID-19) periods, and their characteristics were compared. The first phase was from May 2020 to January 2021 and the second wave was from March 2021 to August 2021. Results A mortality rate of 23.84% (874 deaths among 3666 patients) and 1.36% (232 deaths among 17 000 patients) was noted …

Heart And Timi Scores Predict Severe Coronary Atherosclerosis In Patients With End-Stage Renal Disease, Trishna B Parikh, Moez Aziz, Samuel P Mackoff, Gabriel M Aisenberg

Journal Articles

Objectives History, EKG, age, risk factors, and troponin (HEART) and thrombolysis in myocardial infarction (TIMI) risk calculators have been validated to predict the risk of subsequent acute coronary syndromes and in some studies, severe coronary atherosclerosis in patients with a concerning clinical history. Their performance in patients with end-stage renal disease (ESRD), a population with a high pretest probability for the condition, is unknown. We aimed to determine whether HEART and TIMI scores can predict severe coronary atherosclerosis in patients with end-stage renal disease (ESRD). Methods A single-center retrospective cohort of admitted patients aged 18 years or older with ESRD …

Studying The Therapeutic Effect Of Umbilical Cord Stem Cell In Pneumonia Caused By Covid-19, Salama M. El- Shennawy, Abdalla Abo Hassen, Talal Ibrahim Hagag, Asherf I Zahra, Reham Salama, Mariam A. Fouad

Journal of Medicine in Scientific Research

Context: Coronavirus disease (COVID-19) with severe respiratory morbidity and mortality , rapidly spread all over the world, caused by an sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varying from mild symptoms to pulmonary fibrosis( Li Z et al.,2020). Mesenchymal stem cells (MSCs) can have a critical role, by promoting the pulmonary parenchyma regeneration and subsequently decreasing the symptoms of COVID-19 and help immune system to act against the virus (WHO, 2020).Aim: to evaluate the efficacy and safety of using stem cell in the treatment of COVID-19patients.Setting and design: We performed this case control study during the period from November 2020 …

An Analytical Study Of The Risk Factors Affecting The Platelet Aggregation In Patients With Sepsis, Vishnu Priya, Jitender M. Khunger, Anupma Arora

Journal of Medicine in Scientific Research

Objectives (a) To determine the correlation of platelet count and aggregation with sepsis severity and (b) to find the risk factors affecting the platelet aggregation in sepsis. Patients and methods The present observational cross-sectional study was conducted on 30 patients of sepsis over a period of 18 months. All patients underwent complete blood counts, and platelet aggregation to ADP. Pearson correlation coefficient was used to assess the association of Sequential Organ Failure Assessment (SOFA) score and aggregation to ADP and platelet. Linear regression was done to determine the risk factors affecting platelet aggregation in sepsis. A P value of less …

Mission-Based Filters In The Electronic Residency Application Service: Saving Time And Promoting Diversity, Jennifer L Swails, Sasha Adams, Mark Hormann, Emma Omoruyi, Omowunmi Aibana

Journal Articles

BACKGROUND: Holistic review promotes diversity, but widespread implementation remains limited.

OBJECTIVE: We aimed to develop a practical approach to incorporate holistic review principles in screening applicants in the Electronic Residency Application Service (ERAS) and to assess the impact on diversity.

METHODS: Three residency programs (internal medicine [IM], pediatrics, and surgery) at McGovern Medical School developed filters to identify applicants with experiences/attributes aligned with the institutional mission. These filters were retroactively applied to each program's 2019-2020 applicant pool using built-in ERAS capabilities to group applicants by user-defined features. We compared the demographics of applicants reviewed during the cycle with those identified …

Reorganising For Covid-19 Pandemic: A Review Of Structural Modifications By The Department Of Internal Medicine In Low To Middle-Income Countries, Shakeel Ur Rehman, Muhammad Arslan Ahmed, Ghufran Adnan, Maria Ali Khan

Department of Medicine

Scientists classified the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a novel coronavirus on January 7, 2020. The World Health Organization (WHO) acknowledged the SARS-CoV-2 outburst a public health emergency of international concern on January 30, 2020. Since its origin, this virus has disrupted the best healthcare systems, economies, and strained financial resources; and for underdeveloped countries' healthcare systems, the virus has become a crisis. To tackle the potential hazards from this virus, our Department restructured the services that not only helped us to cope with the pandemic, but also provided an example to copy for other contemporary institutes. …

Which Internal Medicine Clerkship Characteristics Are Associated With Students' Performance On The Nbme Medicine Subject Exam? A Multi-Institutional Analysis., Matthew M. Fitz, William Adams, Steven A. Haist, Karen E. Hauer, Linette P. Ross, Amanda Raff, Gauri Agarwal, T. Robert Vu, Jonathan Appelbaum, Valerie J. Lang, Chad Miller, Cyril Grum, Mark Fagan, Jennifer Foster, Hilary F. Ryder, Bruce Houghton, Ryan Nall, Amy Shaheen, Michael Elnicki, Anna Donovan, Stuart Kiken, Cynthia Ledford, Shobhina Chheda, Doug Paauw, Blake Barker, Maureen Lowery, Nina Mingioni, Deepti Rao, William Kelly

Division of Internal Medicine Faculty Papers & Presentations

PURPOSE: To identify which internal medicine clerkship characteristics may relate to NBME Medicine Subject Examination scores, given the growing trend toward earlier clerkship start dates.

METHOD: The authors used linear mixed effects models (univariable and multivariable) to determine associations between medicine exam performance and clerkship characteristics (longitudinal status, clerkship length, academic start month, ambulatory clinical experience, presence of a study day, involvement in a combined clerkship, preclinical curriculum type, medicine exam timing). Additional covariates included number of NBME clinical subject exams used, number of didactic hours, use of a criterion score for passing the medicine exam, whether medicine exam performance …

Point-Of-Care Ultrasound (Pocus) Workshop For Internal Medicine Residents: A Pre/Post-Training Assessment Of Confidence And Knowledge, Abraham Lee, Cesar Gutierrez, Michelle Lopez

MEDI 9331 Scholarly Activities Clinical Years

Across the country, internal medicine residency training programs are having difficulty figuring out how to optimally implement an effective point-of-care ultrasound training into their respective curricula. This study aimed to assess whether a week-long training course of didactics, followed by hands-on practice, improved both the confidence and knowledge skills of internal medicine residents using point-of-care ultrasound (POCUS). The trainees were asked to complete pre/post-training surveys, which tested their ability to interpret POCUS images and also asked them to score their confidence in using POCUS. Results showed a statistically significant improvement in not only their confidence in using POCUS, but also …

Developing And Evaluating A Remote Quality Assurance System For Point-Of-Care Ultrasound For An Internal Medicine Residency Global Health Track, Steven Fox, Michelle Fleshner, Collin Flanagan, Thomas Robertson, Ayako Wendy Fujita, Divya Bhamidipati, Abdulrahman Sindi, Raghunandan Purushothaman, Thuy Bui

Journal Articles

Background: A quality assurance system is vital when using point-of-care ultrasound (POCUS) to ensure safe and effective ultrasound use. There are many barriers to implementing a quality assurance system including need for costly software, faculty time, and extra work to log images. Methods: With minimal funding or protected faculty time, we successfully developed an effective remote quality assurance system between residents rotating internationally and faculty in the US. Results: 270 total exams were logged using this system (41 per resident over a 7 week period). Over the course of the implementation period, a significant increase was seen in average image …

Which Student Characteristics Are Most Important In Determining Clinical Honors In Clerkships? A Teaching Ward Attending Perspective., Lauren Nicholas Herrera, Ryan Khodadadi, Erinn Schmit, James Willig, Andrew Hoellein, Christopher Knudson, Karen Law, Nina Mingioni, Katherine Walsh, Carlos Estrada, Winter Williams

Division of Internal Medicine Faculty Papers & Presentations

PURPOSE: To explore faculty perspectives on which characteristics of high-performing clerkship students are most important when determining an honors or top grade designation for clinical performance.

METHOD: In 2016-2017, the authors surveyed faculty (teaching ward attendings) for internal medicine clerkships and 1 pediatrics clerkship in inpatient settings at 5 U.S. academic medical centers. Survey items were framed around competencies, 24 student characteristics, and attitudes toward evaluation. Factor analysis examined constructs defining high-performing students.

RESULTS: Of 516 faculty invited, 319 (62%) responded. The top 5 characteristics as rated by respondents were taking ownership, clinical reasoning, curiosity, dependability, and high ethical standards …

Topological Dna Damage, Telomere Attrition And T Cell Senescence During Chronic Viral Infections, Yingjie Ji, Xindi Dang, Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Jaun Zhao, Dechao Cao, Sushant Khanal, Madison Schank, Xiao Y. Wu, Zheng D. Morrison, Yue Zou, Mohamed El Gazzar, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Background: T cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions.

Results: We demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was …

Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity …

P62-Mediated Selective Autophagy Endows Virus-Transformed Cells With Insusceptibility To Dna Damage Under Oxidative Stress, Ling Wang, Mary E. A. Howell, Aryianna Sparks Wallace, Caroline Hawkins, Camri A. Nicksic, Carissa Kohne, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of …

Cancer Screening For Transgender Patients: An Online Case-Based Module, Devin Oller

Internal Medicine Faculty Publications

Introduction: Guidelines recommend that primary care providers complete organ-based routine cancer screening for all transgender patients. Training on critical transgender health topics like cancer screening, as well as residents' confidence in addressing issues their transgender patients may face, remains limited among graduate medical education (GME) programs. Online case-based modules are an effective tool for skills improvement in GME, but their application to transgender health topics has not been assessed.

Methods: I developed a brief online module on cancer screening for transgender patients using Google Forms and offered it to first-year internal medicine residents. The module was optional and asynchronous with …

Hcv-Associated Exosomes Promote Myeloid-Derived Suppressor Cell Expansion Via Inhibiting Mir-124 To Regulate T Follicular Cell Differentiation And Function, Ling Wang, Dechao Cao, Ling Wang, Juan Zhao, Lam Nhat Nguyen, Xindi Dang, Yingjie Ji, Xiao Y. Wu, Zheng D. Morrison, Qian Xie, Mohamed El Gazzar, Shunbin Ning, Jonathon P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Virus-infected cells can regulate non-permissive bystander cells, but the precise mechanisms remain incompletely understood. Here we report that this process can be mediated by transfer of viral RNA-loaded exosomes shed from infected cells to myeloid-derived suppressor cells (MDSCs), which in turn regulate the differentiation and function of T cells during viral infection. Specifically, we demonstrated that patients with chronic hepatitis C virus (HCV) infection exhibited significant increases in T follicular regulatory (TFR) cells and decreases in T follicular helper (TFH) cells. These MDSC-mediated T-cell dysregulations resulted in an increased ratio of TFR/TFH and IL-10 production in peripheral blood. Specifically, co-culture …

Inhibition Of Trf2 Accelerates Telomere Attrition And Dna Damage In Naïve Cd4 T Cells During Hcv Infection, Lam Nhat Nguyen, Juan Zhao, Dechao Cao, Xindi Dang, Ling Wang, Jianqi Lian, Ying Zhang, Zhansheng Jia, Xiao Y. Wu, Zheng Morrison, Qian Xie, Yingjie Ji, Zheng Zhang, Mohammed El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by …

Insufficiency Of Dna Repair Enzyme Atm Promotes Naive Cd4 T-Cell Loss In Chronic Hepatitis C Virus Infection, Juan Zhao, Xindi Dang, Peixin Zhang, Lam Nhat Nguyen, Dechao Cao, Lin Wang, Xiaoyuan Wu, Zheng D. Morrison, Ying Zhang, Zhansheng Jia, Qian Xie, Ling Wang, Shunbin Ning, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells have a crucial role in viral clearance and vaccine response; however, the mechanisms regulating their responses to viral infections or vaccinations remain elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA damage, and repair machineries in a large cohort of subjects with hepatitis C virus (HCV) infection. We found that naive CD4 T cells in chronically HCV-infected individuals (HCV T cells) were significantly reduced compared with age-matched healthy subjects. In addition, HCV T cells were prone to apoptosis and DNA damage, as evidenced by increased 8-oxoguanine expression and γH2AX/53BP1-formed DNA damage foci—hallmarks of DNA damage responses. Mechanistically, …

Limd1 Is Induced By And Required For Lmp1 Signaling, And Protects Ebv-Transformed Cells From Dna Damage-Induced Cell Death, Ling Wang, Mary E. A. Howell, Brooke Mcpeak, Katrina Riggs, Carissa Kohne, Jether Uel Yohanon, Daniel E. Foxler, Tyson V. Sharp, Jonathon P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor, being deregulated in many cancers to include hematological malignancies; however, very little is known about the underlying mechanisms of its deregulation and its roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of malignancies of lymphocytic and epithelial origin. Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies. In this study, we have identified potential conserved IRF4- and NFκB-binding motifs in the LIMD1 gene promoter, and both are …

Lmp1 Signaling Pathway Activates Irf4 In Latent Ebv Infection And A Positive Circuit Between Pi3k And Src Is Required, Ling Wang, Junping Ren, Guang Li, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4. As to more precise mechanism, we show that LMP1 physically interacts with c-Src, and the phosphatidylinositol 3 kinase (PI3K) subunit P85 mediates their interaction. Depletion of P85 by …

"Toll-Free" Pathways For Production Of Type I Interferons, Ling Wang, Shunbin Ning

ETSU Faculty Works

Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are recognized by different cellular pathogen recognition receptors (PRRs), which are expressed on cell membrane or in the cytoplasm of cells of the innate immune system. Nucleic acids derived from pathogens or from certain cellular conditions represent a large category of PAMPs/DAMPs that trigger production of type I interferons (IFN-I) in addition to pro-inflammatory cytokines, by specifically binding to intracellular Toll-like receptors or cytosolic receptors. These cytosolic receptors, which are not related to TLRs and we call them "Toll-free" receptors, include the RNA-sensing RIG-I like receptors (RLRs), the DNA-sensing HIN200 family, …

Strategies To Improve Control Of Blood A1c In Diabetics, Jennifer Aronson, Leanne Bellino, Elizabeth Eisenhardt, Diane Bryant, Haley Pelletier, Internal Medicine Team, Adult Outpatient Clinic

Maine Medical Center

A1c monitoring is an important aspect of controlling the health of a diabetic patient. An adult internal medicine clinic noted that the percentage of their diabetic patients who had an A1c higher than 9 or no reading within the past year exceeded the national average. As a result, operational excellence methods were implemented with the overall goal to reduce their percentage to 18% or less.

A root cause analysis identified several deficiencies to includelack of essential equipment, variations in

staff education and the absence of daily reminders.

Post KPI implementations, an overall decrease in the percentage of patients with poorly …

Identification Of Kansarl As The First Cancer Predisposition Fusion Gene Specific To The Population Of European Ancestry Origin, Jeff Xiwu Zhou, Xiaoyan Yang, Shunbin Ning, Ling Wang, Kesheng Wang, Yanbin Zhang, Fenghua Yuan, Fengli Li, David D. Zhuo, Liren Tang, Degen Zhuo

ETSU Faculty Works

Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model. Five of these six KANSARL fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in …

End-Of-Life Training In Us Internal Medicine Residency Programs: A National Study, Derek Cegelka, Timothy R. Jordan, Jiunn-Jye Sheu, Joseph A. Dake, Ragheb Assaly

Faculty Publications

Background: End-of-life care is a required and important component of medical training for internal medicine residents; many of whom will go on to provide care for adults at the end-of-life stage. Although a body of past research suggests that physician training in end-of-life care needs significant improvement, a comprehensive national study of end-of-life education within US internal medicine residency programs has never been published.

Objective: To determine the status of end-of-life education in internal medicine residency programs in the United States.

Method: The study was a cross-sectional, observational study of all internal medicine Residency Program Directors in the US as …

Identification Of Pp1 As The First Phosphatase For Irf7, Shunbin Ning, Ling Wang

ETSU Faculty Works

Excerpt: Interferon (IFN) regulatory factor 7 (IRF7) is phosphorylated and activated in response to pathogenic infections for production of type I IFNs

Viral And Cellular Micrornas In Regulation Of Ebv Latency And Oncogenesis, Ling Wang, Shunbin Ning

ETSU Faculty Works

Epstein-Barr virus (EBV), an oncogenic virus that ubiquitously establishes life-long persistence in humans, encodes viral miRNAs in two clusters, BHRF1 and BART. EBV also regulates expression of a large pool of cellular miRNAs, including miR-155, miR-146a, miR-21, miR-29, and miR-34a. These miRNAs targets both viral and cellular genes involved in the entire viral lifetime from lytic infection to oncogenesis, including viral replication, immune responses, cell cycle regulation, apoptosis, and cell proliferation, and are indispensable for persistent infection, latency establishment and maintenance, and cancer development. Among them, circulating miRNAs and unique miRNA profiles are promising diagnosis and prognosis biomarkers alone or …

Inactivation Of Type I Ifn Jak-Stat Pathway In Ebv Latency, Shunbin Ning, Ling Wang

ETSU Faculty Works

Epstein-Barr Virus (EBV) latent infection is associated with a variety of lymphomas and carcinomas. Interferon (IFN) Regulatory Factors (IRFs) are a family of transcription factors, among which IRF7 is the “master” regulator of type I IFNs (IFN-I) that defends against invading viruses. Robust IFN-I responses require a positive feedback loop between IRF7 and IFN-I. In recent years, we have discovered that IRF7 is significantly induced and activated by the principal EBV oncoprotein--Latent Membrane Protein 1 (LMP1); however, IRF7 fails to trigger robust IFN-I responses in EBV latency. We believe this intriguing finding is critical for EBV latency and oncogenesis, yet …

Expansion Of Myeloid-Derived Suppressor Cells Promotes Differentiation Of Regulatory T Cells In Hiv-1+ Individuals, Ling Wang, Juan Zhao, Junping P. Ren, Xiao Y. Wu, Zheng D. Morrison, Mohamed A. El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Objective: Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood.

Design: In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ Tregs.

Methods: We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by coculturing experiments.

Results: We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy with undetectable viremia, …

Protein Phosphatase 1 Abrogates Irf7-Mediated Type I Ifn Response In Antiviral Immunity, Ling Wang, Juan Zhao, Junping Ren, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN‐α in response to viral infection, and phosphorylation at IRF7 C‐terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)‐binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε‐stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and …

Hcv-Induced Mir146a Controls Socs1/Stat3 And Cytokine Expression In Monocytes To Promote Regulatory T-Cell Development, Junping Ren, Rue S. Ying, Yong Q. Cheng, Ling Wang, Mohamed A. El Gazzar, Guang Y. Li, Shun B. Ning, Jonathon P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up‐regulated in monocytes from hepatitis C virus (HCV )‐infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll‐like receptor (TLR ) stimulation. This miR146a induction by HCV infection …