Medicine and Health Sciences Commons^™

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

A Phase I Study Of Milademetan (Ds3032b) In Combination With Low Dose Cytarabine With Or Without Venetoclax In Acute Myeloid Leukemia: Clinical Safety, Efficacy, And Correlative Analysis, Jayastu Senapati, Muharrem Muftuoglu, Jo Ishizawa, Hussein A Abbas, Sanam Loghavi, Gautam Borthakur, Musa Yilmaz, Ghayas C Issa, Samuel I Dara, Mahesh Basyal, Li Li, Kiran Naqvi, Rasoul Pourebrahim, Elias J Jabbour, Steven M Kornblau, Nicholas J Short, Naveen Pemmaraju, Guillermo Garcia-Manero, Farhad Ravandi, Joseph Khoury, Naval Daver, Hagop M Kantarjian, Michael Andreeff, Courtney D Dinardo

Faculty, Staff and Student Publications

In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. MDM2 inhibitor (MDM2i) monotherapy in AML has shown modest responses in clinical trials but combining options of MDM2i with other potent AML-directed agents like cytarabine and venetoclax could improve its efficacy. We conducted a phase I clinical trial (NCT03634228) to study the safety and efficacy of milademetan (an MDM2i) with low-dose cytarabine (LDAC)±venetoclax in adult patients with relapsed refractory (R/R) or newly diagnosed (ND; unfit) TP53 wild-type AML and performed comprehensive CyTOF analyses to interrogate multiple signaling pathways, the p53-MDM2 …

Anesthetic Considerations For Cardiac Tamponade After Internal Jugular Central Line Placement During Trauma Resuscitation: A Case Report, Kevin M Chen, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

Numerous complications are associated with central venous catheters. Among them, cardiac tamponade is a rare but well-documented catastrophic complication. A 22-year-old healthy male presented with Code 1 trauma resulting from gunshot wounds in the abdomen. Upon examination, he was found to have a large pericardial fluid collection, a large right supraclavicular hematoma, and significant amount of bilateral pleural effusions secondary to extraluminal placement of the right internal jugular central line during resuscitation. After repairing the internal jugular injury and draining the pericardial fluid, the patient was transferred from the intensive care unit to the regular hospital floor. However, 15 days …

The Utility Of Fecal Calprotectin In The Diagnosis And Management Of Microscopic Colitis, Busara Songtanin, Abbie Evans, Kenneth Nugent, Vanessa Costilla

Journal of Community Hospital Internal Medicine Perspectives

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn’s disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis. Methods: The medical records of patients who have been diagnosed with collagenous …

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study., Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Cooper Medical School of Rowan University Departmental Research

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

Hiv/Aids-Related Knowledge, Attitude And Sexual Behaviours Among Undergraduate Students At The Dar Es Salaam University College Of Education, Tanzania, Stephen O. Maluka

Journal of Humanities and Social Sciences

Human Immunodeficiency Virus (HIV) is among the major public health problems facing the world today. While studies have assessed HIV-related knowledge, attitudes and behaviours among college students, evidence shows that HIV prevalence among the youth has been growing at an alarming rate in the past five years. Thus, there is need for more studies to assess young people’s knowledge, attitudes and behaviours on HIV/AIDS in higher learning institutions. This study aimed to assess HIV-related knowledge, sexual attitudes and behaviours, as well as the use of HIV prevention services among students at the Dar es Salaam College of Education (DUCE), in …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy I: Key Ingredients For Bone And Muscle Health, Noelle G. Moreau, Kathleen M. Friel, Robyn K. Fuchs, Sudarshan Dayanidhi, Theresa Sukal-Moulton, Marybeth Grant-Beuttler, Mark D. Peterson, Richard D. Stevenson, Susan V. Duff

Physical Therapy Faculty Articles and Research

Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with …

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …

Homoeopathy In Management Of Chronic Ischaemic Ulcer: An Evidence-Based Case Report, Jayabharathi Srinivasagam, Rohini S, Srinivas Govindarajulu, Tamil Selvi S

Indian Journal of Research in Homoeopathy

Introduction: Ischaemic or arterial ulcer occurs when there is an obstruction in the arterial supply to a particular part of the human body leading to necrosis. These are extremely painful types of chronic wounds. Treating arterial ulcers is a difficult task for the physician since supportive measures such as compression therapy and leg elevation are contraindicated. Surgical intervention is the ultimate approach to manage in conventional medicine. The homoeopathic system of medicine offers a wide range of medicines and a holistic approach to treat such cases non-invasively. Case Summary: A case of a 75-year-old woman who suffered from chronic ischaemic …

G Protein-Coupled Receptor-Targeting Antibody-Drug Conjugates: Current Status And Future Directions, Peyton High, Kendra S Carmon

Faculty, Staff and Student Publications

In recent years, antibody-drug conjugates (ADCs) have emerged as promising anti-cancer therapeutic agents with several having already received market approval for the treatment of solid tumor and hematological malignancies. As ADC technology continues to improve and the range of indications treatable by ADCs increases, the repertoire of target antigens has expanded and will undoubtedly continue to grow. G protein-coupled receptors (GPCRs) are well-characterized therapeutic targets implicated in many human pathologies, including cancer, and represent a promising emerging target of ADCs. In this review, we will discuss the past and present therapeutic targeting of GPCRs and describe ADCs as therapeutic modalities. …

Infant Isolation And Cohorting For Preventing Or Reducing Transmission Of Healthcare-Associated Infections In Neonatal Units, Morcos Hanna, Rita Shah, Lucila Marquez, Rebecca Barzegar, Adrienne Gordon, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Neonatal healthcare-associated infections (HAIs) result in increased morbidity and mortality, as well as increased healthcare costs. Patient isolation measures, i.e. single-room isolation or the cohorting of patients with similar infections, remain a recommended and commonly used practice for preventing horizontal spread of infections in the neonatal intensive care unit (NICU). OBJECTIVES: Our primary objective was to assess the effect of single-room isolation or cohorting, or both for preventing transmission of HAIs or colonization with HAI-causing pathogens in newborn infants less than six months of age admitted to the neonatal intensive care unit (NICU). Our secondary objective was to assess …

Evaluation Of The Orally Bioavailable 4-Phenylbutyrate-Tethered Trichostatin A Analogue Ar42 In Models Of Spinal Muscular Atrophy, Casey J. Lumpkin, Ashlee W. Harris, Andrew J. Connell, Ryan W. Kirk, Joshua A. Whiting, Luciano Saieva, Livio Pellizzoni, Arthur H.M. Burghes, Matthew E.R. Butchbach

Department of Pediatrics Faculty Papers

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a …

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder

School of Graduate Studies Faculty Publications

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study, Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman

School of Medicine Faculty Publications

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = …

Molecular Simulation Of B-Cell Epitope Mapping From Nipah Virus Attachment Protein To Construct Peptide-Based Vaccine Candidate: A Reverse Vaccinology Approach, Viol Dhea Kharisma, Farida Aryani Dian, Pavel Burkov, Pavel Scherbakov, Marina Derkho, Ekaterina Sepiashvili, Teguh Hari Sucipto, Arli Aditya Parikesit, Ahmad Affan Ali Murtadlo, Vikash Jakhmola, Rahadian Zainul

Makara Journal of Science

There are no specific drugs or vaccines for Nipah virus (NiV), which is a new Paramyxovirus that infects swine and humans. This study was conducted to investigate B-cell epitope mapping of the NiV attachment glycoprotein and to construct peptide-based vaccine candidates using the reverse vaccinology approach. To generate the linear B-cell epitope, the NiV isolates were extractad from GenBank, NCBI, using the IEDB web server; peptide modeling was conducted using PEP-FOLD3; docking was conducted using PatchDock and FireDock; and in silico cloning was designed using SnapGene. Various peptides were successfully identified from the NiV attachment glycoprotein based on B-cell epitope …

The Effects Of Covid-19 Lockdown On Social Connectedness And Psychological Distress In Us Adults With Chronic Diseases, Ben King, Omolola E Adepoju, Lechauncy Woodard, Abiodun O Oluyomi, Xiaotao Zhang, Christopher I Amos, Hoda Badr

Faculty, Staff and Students Publications

Lockdown measures enacted in 2020 to control the spread of COVID-19 led to increases in the prevalence of mental health problems. Due to their high-risk status, individuals with chronic diseases may be at increased risk and disproportionately adversely affected by the COVID-19 pandemic. The investigators examined associations between having a high-risk chronic condition, social connectedness, and general distress and COVID-19-specific distress among U.S. adults during the COVID-19 lockdown. Baseline measures of a longitudinal survey collected at the beginning of the pandemic (April to June 2020) were analyzed to identify factors associated with loss of social connectedness from pre- to post-lockdown. …

Researching Covid To Enhance Recovery (Recover) Adult Study Protocol: Rationale, Objectives, And Design, Leora I. Horwitz, Tanayott Thaweethai, Shari B. Brosnahan, Mine S. Cicek, Megan L. Fitzgerald, Jason D. Goldman, Rachel Hess, S. L. Hodder, Vanessa L. Jacoby, Michael R. Jordan, Jerry A. Krishnan, Adeyinka O. Laiyemo, Torri D. Metz, Lauren Nichols, Rachel E. Patzer, Anisha Sekar, Nora G. Singer, Lauren E. Stiles, Barbara S. Taylor, Shifa Ahmed, Heather A. Algren, Khamal Anglin, Lisa Aponte-Soto, Hassan Ashktorab, Ingrid V. Bassett, Brahmchetna Bedi, Nahid Bhadelia

School of Medicine Faculty Publications

Importance SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. …

Secretogranin Iii Selectively Promotes Vascular Leakage In The Deep Vascular Plexus Of Diabetic Retinopathy, Liyang Ji, Prabuddha Waduge, Yan Wu, Chengchi Huang, Avinash Kaur, Paola Oliveira, Hong Tian, Jinsong Zhang, J Timothy Stout, Christina Y Weng, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, induces mosaic patterns of vasculopathy that may be associated with spatial heterogeneity of intraretinal endothelial cells. We recently reported that secretogranin III (Scg3), a neuron-derived angiogenic and vascular leakage factor, selectively binds retinal vessels of diabetic but not healthy mice. Here, we investigated endothelial heterogeneity of three retinal vascular plexuses in DR pathogenesis and the therapeutic implications. Our unique in vivo ligand binding assay detected a 22.7-fold increase in Scg3 binding to retinal vessels of diabetic mice relative to healthy mice. Functional immunohistochemistry revealed that Scg3 predominantly binds …

Sodium-Glucose Cotransporter 2 Inhibitors To Decrease The Uric Acid Concentration-A Novel Mechanism Of Action, Anna Kochanowska, Przemysław Rusztyn, Karolina Szczerkowska, Stanisław Surma, Aleksandra Gąsecka, Miłosz J Jaguszewski, Łukasz Szarpak, Krzysztof J Filipiak

Faculty, Staff and Students Publications

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), …

KCa2 And KCa3.1 Channels In The Airways: A New Therapeutic Target, Razan Orfali, Ali Alfaiz, Mohammad Asikur Rahman, Liz Lau, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

K⁺ channels are involved in many critical functions in lung physiology. Recently, the family of Ca²⁺-activated K⁺ channels (K_Ca) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of K_Ca channels, three small-conductance Ca²⁺-activated K⁺ (K_Ca2) channel subtypes, together with the intermediate-conductance K_Ca3.1 channel, are voltage-independent K⁺ channels, and they mediate Ca²⁺-induced membrane hyperpolarization. Many K_Ca2 channel members are involved in crucial roles in physiological and pathological …

Sirna Drug Delivery Across The Blood–Brain Barrier In Alzheimer's Disease, Muhammad Imran Sajid, Fahad Sultan Sheikh, Faiza Anis, Nourina Nasim, Rachita K. Sumbria, Surya M. Nauli, Rakesh K. Tiwari

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed. We comprehensively report the latest advances in AD pathophysiology, druggable targets, ongoing clinical trials, and the siRNA-based approaches across the blood–brain barrier for addressing …

An Improved Reporter Identifies Ruxolitinib As A Potent And Cardioprotective Camkii Inhibitor, Oscar E Reyes Gaido, Nikoleta Pavlaki, Jonathan M Granger, Olurotimi O Mesubi, Bian Liu, Brian L Lin, Alan Long, David Walker, Joshua Mayourian, Kate L Schole, Chantelle E Terrillion, Lubika J Nkashama, Mohit M Hulsurkar, Lauren E Dorn, Kimberly M Ferrero, Richard L Huganir, Frank U Müller, Xander H T Wehrens, Jun O Liu, Elizabeth D Luczak, Vassilios J Bezzerides, Mark E Anderson

Faculty, Staff and Students Publications

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and …

Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang

Kimmel Cancer Center Faculty Papers

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. …

Pentoxifylline For Treatment Of Sepsis And Necrotising Enterocolitis In Neonates, Mohan Pammi, Khalid N Haque

Faculty, Staff and Students Publications

BACKGROUND: Mortality and morbidity due to neonatal sepsis and necrotising enterocolitis (NEC) remain high despite the use of potent antimicrobial agents. Agents that modulate inflammation may improve outcomes. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is one such agent. This is an update of a review first published in 2003 and updated in 2011 and 2015.

OBJECTIVES: To assess the effectiveness and safety of intravenous PTX as an adjunct to antibiotic therapy on mortality and morbidity in neonates with suspected or confirmed sepsis and neonates with NEC.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registries in July 2022. We …

Comparative Outcomes Of Interventions For Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From The Multicenter Xlpad Registry, Shirling Tsai, Yulun Liu, Lawrence Hoang, Michael Vu, Hua Lu, Bala Ramanan, David Fernandez Vazquez, Zachary Rosol, Sameh Sayfo, Mohamad Amer Alaiti, Panagiotis Koutakis, Emmanouil S Brilakis, Mehdi H Shishehbor, Subhash Banerjee

Faculty, Staff and Student Publications

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional …

Prolylcarboxypeptidase Alleviates Hypertensive Cardiac Remodeling By Regulating Myocardial Tissue Angiotensin Ii, Binh Y Nguyen, Fangchao Zhou, Pablo Binder, Wei Liu, Susanne S Hille, Xiaojing Luo, Min Zi, Hongyuan Zhang, Antony Adamson, Fozia Z Ahmed, Sam Butterworth, Elizabeth J Cartwright, Oliver J Müller, Kaomei Guan, Elizabeth M Fitzgerald, Xin Wang

Faculty, Staff and Student Publications

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1-7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro-X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR-associated protein 9-mediated global prolylcarboxylpeptidase-knockout and adeno-associated virus serotype 9-mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg …

Scutellaria Baicalensis Enhances 5-Fluorouracil-Based Chemotherapy Via Inhibition Of Proliferative Signaling Pathways, Haizhou Liu, Hui Liu, Zhiyi Zhou, Jessica Chung, Guojing Zhang, Jin Chang, Robert A Parise, Edward Chu, John C Schmitz

Abington Jefferson Health Papers

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and …

A Novel Gardnerella, Prevotella, And Lactobacillus Standard That Improves Accuracy In Quantifying Bacterial Burden In Vaginal Microbial Communities, Jacob H. Elnaggar, Caleb M. Ardizzone, Nuno Cerca, Evelyn Toh, Paweł Łaniewski, Rebecca A. Lillis, Melissa M. Herbst-Kralovetz, Alison J. Quayle, Christina A. Muzny, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV) is the most common vaginal dysbiosis. In this condition, a polymicrobial biofilm develops on vaginal epithelial cells. Accurately quantifying the bacterial burden of the BV biofilm is necessary to further our understanding of BV pathogenesis. Historically, the standard for calculating total bacterial burden of the BV biofilm has been based on quantifying Escherichia coli 16S rRNA gene copy number. However, E. coli is improper for measuring the bacterial burden of this unique micro-environment. Here, we propose a novel qPCR standard to quantify bacterial burden in vaginal microbial communities, from an optimal state to a mature BV biofilm. …

Sox7 Deficiency Causes Ventricular Septal Defects Through Its Effects On Endocardial-To-Mesenchymal Transition And The Expression Of Wnt4 And Bmp2, Andrés Hernández-García, Katherine E Pendleton, Sangbae Kim, Yumei Li, Bum J Kim, Hitisha P Zaveri, Valerie K Jordan, Aliska M Berry, M Cecilia Ljungberg, Rui Chen, Rainer B Lanz, Daryl A Scott

Faculty, Staff and Students Publications

SOX7 is a transcription factor-encoding gene located in a region on chromosome 8p23.1 that is recurrently deleted in individuals with ventricular septal defects (VSDs). We have previously shown that Sox7-/- embryos die of heart failure around E11.5. Here, we demonstrate that these embryos have hypocellular endocardial cushions with severely reduced numbers of mesenchymal cells. Ablation of Sox7 in the endocardium also resulted in hypocellular endocardial cushions, and we observed VSDs in rare E15.5 Sox7flox/-;Tie2-Cre and Sox7flox/flox;Tie2-Cre embryos that survived to E15.5. In atrioventricular explant studies, we showed that SOX7 deficiency leads to a severe reduction in endocardial-to-mesenchymal transition (EndMT). RNA-seq …

Comparative Analyses Of The Clinicopathologic Features Of Short-Term And Long-Term Survivors Of Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreatoduodenectomy, Tom Z Liang, Matthew H G Katz, Laura R Prakash, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Suprateek Kundu, Huamin Wang

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15-60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated …