Medical Specialties Commons^™

The Neglect Of Kwashiorkor, Thaddaeus May, Esther Babirekere-Iriso, Mamady Traoré, Emmanuel Berbain, Maimuna Ahmed, Beatrice Amadi, André Briend, Mark Manary, Aminata Shamit Koroma, Neil Hanchard, Mette Frahm Olsen, Henrik Friis, George Praygod, Tsinuel Girma, Moustapha Moussa, Aboubacar Mahamadou, Peter Hotez, Haoua Seini Sabo

Faculty, Staff and Students Publications

No abstract provided.

Preface: Pediatric Plastic Surgery, Larry H Hollier

Faculty, Staff and Students Publications

No abstract provided.

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

Trends And Perspectives For Improving Quality Of Chronictrends And Perspectives For Improving Quality Of Chronic Kidney Disease Care: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference Kidney Disease Care: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Kai-Uwe Eckardt, Cynthia Delgado, Hiddo J L Heerspink, Roberto Pecoits-Filho, Ana C Ricardo, Bénédicte Stengel, Marcello Tonelli, Michael Cheung, Michel Jadoul, Wolfgang C Winkelmayer, Holly Kramer, Conference Participants

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts …

Racial And Ethnic Variation In Ecmo Utilization And Outcomes In Pediatric Cardiac Icu Patients, Marissa A Brunetti, Heather M Griffis, Michael L O'Byrne, Andrew C Glatz, Jing Huang, Kurt R Schumacher, David K Bailly, Yuliya Domnina, Javier J Lasa, Michael Alice Moga, Hayden Zaccagni, Janet M Simsic, J William Gaynor

Faculty, Staff and Students Publications

Background: Previous studies have reported racial disparities in extracorporeal membrane oxygenation (ECMO) utilization in pediatric cardiac patients.

Objectives: The objective of this study was to determine if there was racial/ethnic variation in ECMO utilization and, if so, whether mortality was mediated by differences in ECMO utilization.

Methods: This is a multicenter, retrospective cohort study of the Pediatric Cardiac Critical Care Consortium clinical registry. Analyses were stratified by hospitalization type (medical vs surgical). Logistic regression models were adjusted for confounders and evaluated the association between race/ethnicity with ECMO utilization and mortality. Secondary analyses explored interactions between race/ethnicity, insurance, and socioeconomic status …

Emergent Radiotherapy For Brain And Leptomeningeal Metastases: A Narrative Review, Andrew B Barbour, Peter Zaki, Tresa M Mcgranahan, Vyshak Venur, Balamurugan Vellayappan, Joshua Palmer, Lia M Halasz, Jonathan T Yang, Molly Blau, Yolanda D Tseng, Samuel T Chao, John H Suh, Matthew Foote, Kristin J Redmond, Stephanie E Combs, Eric L Chang, Arjun Sahgal, Simon S Lo

Faculty, Staff and Students Publications

Background and objective: As novel systemic therapies allow patients to live longer with cancer, the risk of developing central nervous system (CNS) metastases increases and providers will more frequently encounter emergent presentation of brain metastases (BM) and leptomeningeal metastases (LM). Management of these metastases requires appropriate work-up and well-coordinated multidisciplinary care. We set out to perform a review of emergent radiotherapy (RT) for CNS metastases, specifically focusing on BM and LM.

Methods: We review the appropriate pathways for workup and initial management of BM and LM, while reviewing the literature supporting emergent treatment of these entities with surgery, systemic anti-cancer …

Anthocyanins: Molecular Aspects On Their Neuroprotective Activity, César A Zaa, Álvaro J Marcelo, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lower the risk of neurodegenerative diseases. Anthocyanins exhibit neuroprotective effects that could potentially alleviate symptoms associated with such diseases. In this review, we compiled and discussed a large body of evidence supporting the neuroprotective role of anthocyanins. Our examination encompasses human studies, animal models, …

Braf Inhibitors In Metastatic Colorectal Cancer And Mechanisms Of Resistance: A Review Of The Literature, Patricia Guerrero, Víctor Albarrán, María San Román, Carlos González-Merino, Coral García De Quevedo, Jaime Moreno, Juan Carlos Calvo, Guillermo González, Inmaculada Orejana, Jesús Chamorro, Íñigo Martínez-Delfrade, Blanca Morón, Belén De Frutos, María Reyes Ferreiro

Faculty, Staff and Students Publications

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.

A Small-Molecule Inhibitor Of Topbp1 Exerts Anti-Myc Activity And Synergy With Parp Inhibitors, Fang-Tsyr Lin, Kang Liu, Lidija A Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, Shwu-Jiuan Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

We have previously identified TopBP1 (topoisomerase IIβ-binding protein 1) as a promising target for cancer therapy, given its role in the convergence of Rb, PI(3)K/Akt, and p53 pathways. Based on this, we conducted a large-scale molecular docking screening to identify a small-molecule inhibitor that specifically targets the BRCT7/8 domains of TopBP1, which we have named 5D4. Our studies show that 5D4 inhibits TopBP1 interactions with E2F1, mutant p53, and Cancerous Inhibitor of Protein Phosphatase 2A. This leads to the activation of E2F1-mediated apoptosis and the inhibition of mutant p53 gain of function. In addition, 5D4 disrupts the interaction of TopBP1 …

Food Insecurity Increases Risk Of Depression And Anxiety Among Women In Senegal Living With Diabetes And/Or Hypertension, Rachel P Allred, Ndèye Aminata Mbaye, Fatoumata Diagne, Sheryl A Mccurdy, Melissa B Harrell, Emma Nelson Bunkley

Faculty, Staff and Student Publications

Food insecurity affects close to half the population of Senegal, West Africa, a country simultaneously affected by the ongoing global diabetes pandemic. Diabetes and food insecurity are associated with adverse mental health, yet research exploring the relationship between chronic physical illness, food insecurity, and mental illness in Senegal is currently lacking. The objective of this study was to investigate the association between food insecurity and depression and anxiety, separately, in Senegalese women living with diabetes and hypertension. Food insecurity was measured using the Household Food Insecurity Access Scale. Occurrence of depression and anxiety symptoms was assessed using the Modified Hopkins …

The Influence Of Obesity On Outcomes With Immune Checkpoint Blockade: Clinical Evidence And Potential Biological Mechanisms, Andrew W Hahn, Neha Venkatesh, Pavlos Msaouel, Jennifer L Mcquade

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) is a mainstay of treatment for advanced cancer, yet tumor response and host toxicity are heterogenous in those patients who receive ICB. There is growing interest in understanding how host factors interact with tumor intrinsic properties and the tumor microenvironment to influence the therapeutic index with ICB. Obesity, defined by body mass index, is a host factor associated with improved outcomes in select cancers when treated with ICB. While the biological mechanism for this obesity paradox is not fully understood, pre-clinical and translational studies suggest obesity may potentially impact tumor metabolism, inflammation, and angiogenesis. Herein, we …

Correction: Microrna 603 Acts As A Tumor Suppressor And Inhibits Triple-Negative Breast Cancer Tumorigenesis By Targeting Elongation Factor 2 Kinase, Recep Bayraktar, Martin Pichler, Pinar Kanlikilicer, Cristina Ivan, Emine Bayraktar, Nermin Kahraman, Burcu Aslan, Serpil Oguztuzun, Mustafa Ulasli, Ahmet Arslan, George Calin, Gabriel Lopez-Berestein, Bulent Ozpolat

Faculty, Staff and Student Publications

No abstract provided.

Daily Fosfomycin Versus Levofloxacin For Complicated Urinary Tract Infections, Nadine Rouphael, Patricia Winokur, Michael C Keefer, Jessica Traenkner, Ana Drobeniuc, Yohei Doi, Sonal Munsiff, Vance G Fowler, Scott Evans, Randolph E Oler, Bonifride Tuyishimire, Marina Lee, Varduhi Ghazaryan, Henry F Chambers

Faculty, Staff and Student Publications

Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.

The Uncharted Role Of Her2 Mutant Alleles In Breast Cancer, Rashi Kalra, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.

Tgf-Β1 In Aplysia: Role In Long-Term Changes In The Excitability Of Sensory Neurons And Distribution Of Tβr-Ii-Like Immunoreactivity, Muhammad S Khan, Eun Kim, Quentin Le Hingrat, Adam Kleinman, Alessandro Ferrari, Jose C Sammartino, Elena Percivalle, Cuiling Xu, Shaohua Huang, Thomas W Kenniston, Irene Cassaniti, Fausto Baldanti, Ivona Pandrea, Andrea Gambotto, Cristian Apetrei

Faculty, Staff and Student Publications

The study provides important insights into the immunogenicity and efficacy of a tetravalent protein subunit vaccine candidate against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine induced both humoral and cellular immune responses in nonhuman primates with controlled SIVagm infection and was able to generate Omicron variant-specific antibodies without specifically vaccinating with Omicron. These findings suggest that the tetravalent composition of the vaccine candidate could provide broad protection against multiple SARS-CoV-2 variants while minimizing the risk of immune escape and the emergence of new variants. Additionally, the use of rhesus macaques with controlled SIVsab infection may better represent vaccine …

Development Of A New Travellers’ Diarrhoea Clinical Severity Classification And Its Utility In Confirming Rifamycin-Sv Efficacy, Herbert L Dupont, June S Almenoff, Mansi S Jamindar, Enoch Bortey, Robert Steffen

Faculty, Staff and Student Publications

BACKGROUND: travellers' diarrhoea (TD) is frequently reported with incidence up to 40% in high-risk destinations. Previous studies showed that the number of loose stools alone is inadequate to holistically predict the severity of TD. To improve the prediction of prognosis and to optimize treatments, a simple risk-based clinical severity classification has been developed.

METHODS: pooled baseline data of signs and symptoms and number of loose stools from 1098 subjects enrolled in two double-blind Phase 3 trials of rifamycin-SV were analyzed with correlation, multiple correspondence analyses, prognostic factor criteria, and Contal and O'Quigley method to generate a TD severity classification (mild, …

Sdc1 And Itga2 As Novel Prognostic Biomarkers For Pdac Related To Ipmn, Chuan-Long Zhang, Qian Shen, Fu-Dong Liu, Fan Yang, Meng-Qi Gao, Xiao-Chen Jiang, Yi Li, Xi-Yuan Zhang, Ge-Er En, Xue Pan, Bo Pang

Faculty, Staff and Student Publications

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package 'limma.' A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable …

Early Antibody Treatment, Inflammation, And Risk Of Post-Covid Conditions, Kelly A Gebo, Sonya L Heath, Yuriko Fukuta, Xianming Zhu, Sheriza Baksh, Allison G Abraham, Feben Habtehyimer, David Shade, Jessica Ruff, Malathi Ram, Oliver Laeyendecker, Reinaldo E Fernandez, Eshan U Patel, Owen R Baker, Shmuel Shoham, Edward R Cachay, Judith S Currier, Jonathan M Gerber, Barry Meisenberg, Donald N Forthal, Laura L Hammitt, Moises A Huaman, Adam Levine, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Shweta Anjan, Thomas Gniadek, Seble Kassaye, Janis E Blair, Karen Lane, Nichol A Mcbee, Amy L Gawad, Piyali Das, Sabra L Klein, Andrew Pekosz, Evan M Bloch, Daniel Hanley, Arturo Casadevall, Aaron A R Tobian, David J Sullivan, Cssc-004 Consortium

Faculty, Staff and Students Publications

Post-COVID conditions (PCCs) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about treatment, inflammation, and PCC. Among 882 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of COVID-19 convalescent plasma (CCP) vs control plasma with available biospecimens and symptom data, the association between early CCP treatment, cytokine levels, and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14, and day 90 using a multiplexed sandwich immunoassay (Meso Scale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. …

Returning Incidentally Discovered Hepatitis C Rna-Seq Results To Copdgene Study Participants, Edwin K Silverman, Arthur Y Kim, Barry J Make, Elizabeth A Regan, Jarrett D Morrow, Craig P Hersh, James O'Brien, James D Crapo, Nadia N Hansel, Gerard Criner, Eric L Flenaugh, Douglas Conrad, Richard Casaburi, Russell P Bowler, Nicola A Hanania, R Graham Barr, Surya P Bhatt, Frank C Sciurba, Antonio Anzueto, Meilan K Han, Charlene E Mcevoy, Alejandro P Comellas, Dawn L Demeo, Richard Rosiello, Jeffrey L Curtis, Tricia Uchida, Carla Wilson, P Pearl O'Rourke

Faculty, Staff and Students Publications

The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed …

Toll-Like Receptor 4 And Cd11b Expressed On Microglia Coordinate Eradication Of Candida Albicans Cerebral Mycosis, Yifan Wu, Shuqi Du, Lynn H Bimler, Kelsey E Mauk, Léa Lortal, Nessim Kichik, James S Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P Richardson, Bernhard Hube, Julian R Naglik, David B Corry

Faculty, Staff and Students Publications

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. …

Constitutive Interleukin-7 Cytokine Signaling Enhances The Persistence Of Epstein-Barr Virus-Specific T-Cells, Sandhya Sharma, Tim Sauer, Bilal A Omer, Thomas Shum, Lisa A Rollins, Cliona M Rooney

Faculty, Staff and Students Publications

The efficacy of therapeutic T-cells is limited by a lack of positive signals and excess inhibitory signaling in tumor microenvironments. We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing chimeric antigen receptors (CARs), and C7R-modified GD2.CAR T-cells are currently undergoing clinical trials. To determine if the C7R could also enhance the activity of T-cells recognizing tumors via their native T-cell receptors (TCRs), we evaluated its effects in Epstein–Barr virus (EBV)-specific T-cells (EBVSTs) that have produced clinical benefits in patients with EBV-associated malignancies. EBVSTs were generated by stimulation of peripheral …

Mga-Seq: Robust Identification Of Extrachromosomal Dna And Genetic Variants Using Multiple Genetic Abnormality Sequencing, Da Lin, Yanyan Zou, Xinyu Li, Jinyue Wang, Qin Xiao, Xiaochen Gao, Fei Lin, Ningyuan Zhang, Ming Jiao, Yu Guo, Zhaowei Teng, Shiyi Li, Yongchang Wei, Fuling Zhou, Rong Yin, Siheng Zhang, Lingyu Xing, Weize Xu, Xiaofeng Wu, Bing Yang, Ke Xiao, Chengchao Wu, Yingfeng Tao, Xiaoqing Yang, Jing Zhang, Sheng Hu, Shuang Dong, Xiaoyu Li, Shengwei Ye, Zhidan Hong, Yihang Pan, Yuqin Yang, Haixiang Sun, Gang Cao

Children’s Nutrition Research Center Staff Publications

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.

Association Of Dcis Size And Margin Status With Risk Of Developing Breast Cancer Post-Treatment: Multinational, Pooled Cohort Study, Renée S J M Schmitz, Alexandra W Van Den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, Danalyn Byng, Thomas Lynch, Brian A Menegaz, Deborah Collyar, Terry Hyslop, Samantha Thomas, Jason K Love, Michael Schaapveld, Proteeti Bhattacharjee, Marc D Ryser, Elinor Sawyer, E Shelley Hwang, Alastair Thompson, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt

Faculty, Staff and Student Publications

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.

DESIGN: Multinational, pooled cohort study.

SETTING: Four large international cohorts.

PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both.

MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative …

Diaph1-Mfn2 Interaction Regulates Mitochondria-Sr/Er Contact And Modulates Ischemic/Hypoxic Stress, Gautham Yepuri, Lisa M Ramirez, Gregory G Theophall, Sergei V Reverdatto, Nosirudeen Quadri, Syed Nurul Hasan, Lei Bu, Devi Thiagarajan, Robin Wilson, Raquel López Díez, Paul F Gugger, Kaamashri Mangar, Navneet Narula, Stuart D Katz, Boyan Zhou, Huilin Li, Aleksandr B Stotland, Roberta A Gottlieb, Ann Marie Schmidt, Alexander Shekhtman, Ravichandran Ramasamy

Faculty, Staff and Student Publications

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. …

Recent Advances In The Synthesis And Antioxidant Activity Of Low Molecular Mass Organoselenium Molecules, João M Anghinoni, Paloma T Birmann, Marcia J Da Rocha, Caroline S Gomes, Michael J Davies, César A Brüning, Lucielli Savegnago, Eder J Lenardão

Faculty, Staff and Student Publications

Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

Enolase Inhibitors As Early Lead Therapeutics Against Trypanosoma Brucei, Colm P Roster, Danielle Lavigne, Jillian E Milanes, Emily Knight, Heidi D Anderson, Sabrina Pizarro, Elijah M Harding, Meredith T Morris, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian Dominy, Daniel C Whitehead, Md Nasir Uddin, Steven W Millward, James C Morris

Faculty, Staff and Student Publications

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) …

Determining Call-To-Entry Rate And Recruitment Barriers In Clinical Studies For Community Clinics Serving Low-Income Populations: A Cohort Study, Elizabeth M Vaughan, Salim Virani, Mahmoud Al Rifai, Victor J Cardenas, Craig A Johnston, Laura Porterfield, Zuleica Santiago Delgado, Susan L Samson, Vanessa Schick, Aanand D Naik

Faculty, Staff and Student Publications

BACKGROUND: Recruitment for clinical studies is challenging. to overcome barriers, investigators have previously established call-to-entry rates to assist in planning. However, rates specific to low-income minority populations are needed to account for additional barriers to enrolment these individuals face.

OBJECTIVE: to obtain a call-to-entry rate in a low-income uninsured Hispanic population with chronic disease.

METHODS: We used data from four of our randomised clinical studies to determine the call-to-entry rate for individuals (n=1075) with or at risk for type 2 diabetes: participants needed/potential participants contacted=recruitment rate (yield). Research staff contacted potential participants to enrol in a study that evaluated 6 …

The Lin28b/Wnt5a Axis Drives Pancreas Cancer Through Crosstalk Between Cancer Associated Fibroblasts And Tumor Epithelium, Zhaoqi Shu, Minghe Fan, Bo Tu, Zhiheng Tang, Haojie Wang, Haimeng Li, Hengchao Li, Meng Yuan, Jingru Bai, Sihan Huo, Lina Wang, Wei-Guo Zhu, Wei Wang, Xiaoyun Liu, Shaokun Shu, Ying Zhao

Faculty, Staff and Student Publications

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in …

Neuroprotective Agents With Therapeutic Potential For Covid-19, César A Zaa, Clara Espitia, Karen L Reyes-Barrera, Zhiqiang An, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate …

A New Dietary Fiber Can Enhance Satiety And Reduce Postprandial Blood Glucose In Healthy Adults: A Randomized Cross-Over Trial, Simou Wu, Wen Jia, Huimin He, Jun Yin, Huilin Xu, Chengyuan He, Qinqiu Zhang, Yue Peng, Ruyue Cheng

Faculty, Staff and Student Publications

BACKGROUND: Dietary fiber plays a potential role in regulating energy intake and stabilizing postprandial blood glucose levels. Soluble dietary fiber has become an important entry point for nutritional research on the regulation of satiety.

METHODS: this was a double-blind, randomized cross-over trial enrolling 12 healthy subjects to compare the effects of RPG (R+PolyGly) dietary fiber products (bread, powder, and capsule) and pectin administered with a standard meal on satiety, blood glucose, and serum insulin level.

RESULTS: Adding 3.8% RPG dietary fiber to bread significantly increased the volume, water content, hardness, and chewiness of bread compared to 3.8% pectin bread and …