Chemicals and Drugs Commons^™

Influence And Excess: A Study Of Alcohol’S Governmental, Societal, Biochemical, And Enzymatic Impact In The U.S And Other Countries Around The World, Thomas W. Snider

Senior Honors Theses

The conduct of the thesis is to explore the intricacies of alcohol consumption. The thesis will outline the history of alcohol and the societal pressures and conduct of drinking with relation to the government. After the history of alcohol has been defined, the thesis will move into the chemistry portion, delineating the absorption, digestion, metabolism, and excretion of alcohol. This is the portion of the thesis that will contain the quantitative data and source material as much research has already been conducted regarding these components of alcohol consumption. The condition of the research is that the data will be collected …

Breastfeeding Safety Following Maternal Anesthesia: A Guideline Development, Megan Honea, Mary Johnson

Doctoral Projects

Recommendations regarding breastfeeding following maternal anesthesia are inconsistent and often not up to date with current best practice guidelines. Previous recommendations have led to mothers unnecessarily “pumping and dumping” breast milk has benefits for both mother and baby. These benefits include (a) increasing the infant’s access to colostrum, (b) encouraging mother-baby bonding, (c) improving the mother’s breastfeeding experience, (d) and providing significant health benefits to the infant. The purpose of this scholarly project was to develop a set of evidence-based recommendations that focus on mothers who desire to breastfeed following general anesthesia. These recommendations will highlight maternal- fetal transfer of …

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos

School of Graduate Studies Faculty Publications

Leukemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) known for its specificity toward Ras homolog family member A (RhoA). LARG plays a crucial regulatory role in various cellular processes such as migration, proliferation, invasion, and metastasis by facilitating the exchange of GDP to GTP on RhoA. Phosphorylation of LARG at S1288 by ribosomal S6 kinase 2 (RSK2) promotes RhoA activation. However, the precise mechanism remains unclear. Here, we demonstrate the essential role and mechanism by which S1288 phosphorylation facilitates LARG-mediated invasiveness in response to epidermal growth factor (EGF). Upon EGF stimulation, RSK2 phosphorylates LARG at S1288, thereby promoting …

Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi

School of Graduate Studies Faculty Publications

Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …

Aberrant Expression Of A Disintegrin And Metalloproteinase With Thrombospondin Motifs 13 (Adamts13) In Pancreatic Cancer Leads To Dichotomic Functions, Stephanie Allmang, Hagen R. Witzel, Anne Hausen, Simone Marquard, Christoph Eckert, Nicole Marnet, Nina Hörner, Philipp Mayer, Stefan Heinrich, Hien Dang, Wilfried Roth, Matthias M. Gaida

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers characterized by highly invasive growth into the surrounding peripancreatic fat tissue, where tumor cells can directly interact with adipocytes. Due to poor response to the currently available (radio)chemotherapies, there is an urgent need for advanced therapy concepts. The present study shows that ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a key factor in blood coagulation, is significantly overexpressed in human PDAC. Immunohistochemical analysis revealed that ADAMTS13 expression is associated with prolonged survival and negatively correlated with vascular density. In vitro and in vivo experiments demonstrate its partial …

Human Kallikrein 2: A Novel Lineage-Specific Surface Target In Prostate Cancer, Fei Shen, Ryan Smith, Theresa Mcdevitt, Krista Menard, Shaozhou Tian, Gerald Chu, Ruchi Chaudhary, Jennifer Mccann, Halley Oyer, Sherry C. Wang, Steven Max, Peter Francis, William K. Kelly, Charles G. Drake

Kimmel Cancer Center Faculty Papers

PURPOSE: Targeted therapies for metastatic prostate cancer are limited, highlighting the need for novel drug targets and mechanisms of action (MoA). Human kallikrein 2 (KLK2) is a prostate-specific antigen expressed across the prostate cancer disease continuum. However, it was not recognized as a therapeutic target for prostate cancer in the past due to limited evidence of its cell surface expression. In this study, we systematically characterized KLK2 expression in prostate cancer, confirmed its cell surface expression, and demonstrated the preclinical efficacy of three KLK2-targeting therapeutics with distinct MoA.

EXPERIMENTAL DESIGN: The KLK2 expression profile in different stages of prostate cancer …

Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali

School of Graduate Studies Faculty Publications

The field of non-coding RNA research is advancing at a breathtaking pace, continually uncovering new layers of regulatory complexity and functional diversity [...].

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Overview Of Exosomal Non-Coding Rnas In Cardiovascular Disease Using High Throughput Sequencing, Mortaza Eivazi, Leila Abkhooie, Kamran Hosseini, Parnia Mobasheran, Tahereh Ebrahimi, Vahideh Tarhriz, Eric Lazartigues

School of Graduate Studies Faculty Publications

Non-coding RNAs including miRNAs, long-ncRNAs, and circular RNAs play crucial roles in cell-to-cell communication and epigenetic regulation. They control gene expression at multiple levels, including transcriptional, post-transcriptional, and translational, thereby influencing associated signaling pathways. Encapsulated within exosomes, micro-vesicles, and apoptotic bodies, ncRNAs can be transported between cells while being protected from harsh environmental conditions. Studies have shown various expression patterns across different cell types and in various physiological and pathological states. However, the precise correlations and extent of their contribution to diseases are still under investigation. Recent studies have reported the involvement of extracellular vesicle-associated ncRNAs in the pathogenesis of …

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Computational Insights Into The Structural Basis For Reduced Hepatotoxicity Of Novel Nonopioid Analgesics, Claire Coderch, Hernan A. Bazán, Nicolas G. Bazan, Bhattacharjee Surjyadipta, Julio Alvarez-Builla, Beatriz De Pascual-Teresa

School of Graduate Studies Faculty Publications

Acetaminophen (ApAP) toxicity arises from the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI), a degradation product known to cause significant liver damage and kidney injury. This toxicity is a major concern associated with the widespread use of ApAP, a commonly used nonsteroidal anti-inflammatory drug. To address this important issue, a series of novel nonopioid analgesic candidates with reduced toxicity have been recently reported. However, the molecular and atomic-level mechanisms underlying their decreased toxicity remain largely unexplored. In this study, computational analyses is performed to investigate the dynamic behavior, physicochemical properties, and ligand-receptor interactions of these new chemical entities (NCEs). The findings provide …

Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a psychiatric disorder characterized by escalated alcohol use and the emergence of negative affective symptoms. Studies have described a dysregulation of glucocorticoid receptor (GR) signaling in the context of AUD at the levels of the hypothalamic-pituitary-adrenal (HPA) axis and central amygdala (CeA). A functional increase in CeA GR activity occurs during alcohol withdrawal in alcohol-dependent animal models, and the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in both rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment in …

Fine Mapping Regulatory Variants By Characterizing Native Cpg Methylation With Nanopore Long-Read Sequencing, Yijun Tian, Shannon K. Mcdonnell, Lang Wu, Nicholas B. Larson, Liang Wang

School of Medicine Faculty Publications

5-Methylcytosine (5mC) is the most common DNA modification in the human genome. Bisulfite conversion combined with short-read sequencing captures this modification at single-nucleotide resolution but introduces PCR duplication bias and limits co-methylation analysis between distant cytosines. To resolve these limitations, we used nanopore long-read sequencing to profile human methylation and performed long-range co-methylation analysis with native DNA modification information. We analyzed the nanopore demo data in the adaptive sampling sequencing targeting the CpG islands and applied the linkage disequilibrium (LD) R to identified methylation haplotype blocks (MHBs). We found that the cancer genome exhibited significantly smaller MHBs, higher CpG density, …

Regorafenib Pulmonary Toxicity: A Case Of Cavitary Lung Disease And Ards Treated With Infliximab, Michael Dong, Mackenzie Kramer, Tanmay Gandhi, Gautam George

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Regorafenib-induced pneumonitis and acute respiratory distress syndrome (ARDS) are rare and poorly characterized toxicities. We describe a 43-year-old male with metastatic colorectal cancer who developed hypoxic respiratory failure after two cycles of regorafenib. Imaging revealed cavitary lung lesions and diffuse ground glass opacities. Despite antibiotics and high-dose corticosteroids, his condition deteriorated, requiring ICU admission and mechanical ventilation. Bronchoalveolar lavage revealed bacterial pathogens, and he was treated for pneumonia. After multidisciplinary discussion, he was assessed to have regorafenib-induced pneumonitis as a major driver of his respiratory failure, and after limited steroid response, infliximab was administered with marked respiratory improvement. However, he …

Large Language Models As Information Providers For Appropriate Antimicrobial Use: Computational Text Analysis And Expert-Rated Comparison Of Chatgpt, Claude And Gemini, Marcello Di Pumpo, Maria Rosaria Gualano, Danilo Buonsenso, Francesca Raffaelli, Daniele Donà, Vittorio Maio, Patrizia Laurenti, Walter Ricciardi, Leonardo Villani

College of Population Health Faculty Papers

OBJECTIVES: Antimicrobial resistance is a critical public health threat. Large language models (LLMs) show great capability for providing health information. This study evaluates the effectiveness of LLMs in providing information on antibiotic use and infection management.

METHODS: Using a mixed-method approach, responses to healthcare expert-designed scenarios from ChatGPT 3.5, ChatGPT 4.0, Claude 2.0 and Gemini 1.0, in both Italian and English, were analysed. Computational text analysis assessed readability, lexical diversity and sentiment, while content quality was assessed by three experts via DISCERN tool.

RESULTS: 16 scenarios were developed. A total of 101 outputs and 5454 Likert-scale (1-5) scores were obtained …

Effectiveness Of Vitamin D3 In Facilitating The Therapeutic Progression Of Healing Diabetic Foot Ulcers, Fatemeh Nouri, Sara Aghaei, Gülüzar Özbolat, Yusuf Döğüş, Mahdi Mirhamidi, Reza Rahimi Barghani, Amin Daemi

Chulalongkorn Medical Journal

Background: Today’s, diabetes and its complications have afflicted a large population all over the world, so that it is estimated that its prevalence in all age groups will reach from 2.8% in 2000 to 4.4% in 2030. It is well known that vitamin D may cause rapid wound healing and anti-inflammatory.

Objective: Regarding the importance of the quality of life of diabetic patients and the improvement of chronic diabetic foot ulcers, this paper aims to investigate the efficacy of vitamin D3 on the healing of diabetic foot ulcers. The present research is conducted as a randomized controlled trial.

Methods: …

Advancing Peptide-Based Vaccines Against Candida: A Comparative Perspective On Liposomal And Synthetic Formulations, Hong Xin

School of Graduate Studies Faculty Publications

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform's compatibility with clinically approved adjuvants (MPLA and QS-21), …

Neuronal Activity-Dependent Gene Dysregulation In C9orf72 I3neuronal Models Of Als/Ftd Pathogenesis, Layla T. Ghaffari, Emily A. Welebob, Sarah E. Bond Newton, Ashley V. Boehringer, Kelly L. Cyliax, Piera Pasinelli, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9ORF72 (C9) gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE-induced pluripotent stem cell-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization or a blockade of K⁺ channels, followed by RNA sequencing, induces …

Predictive Gene Expression Signatures For Alzheimer's Disease Using Post-Mortem Brain Tissue, Ashley Duche, Oliver Tan, Andrius Baskys, Rachita K. Sumbria, Moom R. Roosan

Pharmacy Faculty Articles and Research

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau protein aggregates in the brain. These pathological features manifest in specific regions, but mechanisms rendering some areas more susceptible to early AD-related changes remain poorly understood. To address this, we developed predictive gene expression signatures to explore molecular mechanisms underlying regional vulnerability to AD pathology.

Methods: Post-mortem brain tissues from participants of the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) were used to derive gene expression signatures from six brain regions affected at varying …

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Comparison Of Authentic Urine N-Ethylpentedrone Metabolites To Predicted In Silico And In Vitro Human Hepatocyte Metabolism, Gloria Daziani, Omayema Taoussi, Diletta Berardinelli, Giulia Bambagiotti, Marilyn A. Huestis, Francesco P. Busardò, Jeremy Carlier

Institute of Emerging Health Professions Faculty Papers

Synthetic cathinones are the second most common class of substances belonging to the category of new psychoactive substances (NPS). N-ethylpentedrone (NEPD) self-administration was reported, making it important to elucidate its metabolic pathway to improve its detection. NEPD is often taken together with other substances; confidently identifying its intake is important for accurate toxicological analysis and understanding its toxicity. NEPD metabolism was studied following incubation with human hepatocytes and analysis by liquid chromatography-high-resolution mass spectrometry paired with Compound Discoverer software (Thermo Fisher Scientific). Prediction of possible metabolites was performed with the online software GLORYx. In vivo NEPD metabolism was evaluated by …

Ybx1-Mediated Activation Of Srebp2 Drives Sorafenib Resistance Via Cholesterol Biosynthesis In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard, Ana Ayala Pazzi, Shaibir Hussain, Salique H. Shaham, Manish Tripathi

Research Colloquium

Background: Hepatocellular carcinoma (HCC) is an aggressive, largely chemo-resistant cancer with a poor prognosis and is the leading cause of cancer-related deaths worldwide. Currently, there is no effective systemic chemotherapy for HCC. Sorafenib is a multikinase inhibitor commonly used as the first-line treatment for advanced HCC. However, acquired drug resistance significantly limits its clinical effectiveness. The Y-box binding protein (YBX1) is an oncogenic RNA-binding protein found to be upregulated in sorafenib-resistant HCC cells and tissues.

Methods: HCC model SK Hep1, YBX1 overexpression, and knockdown cells were prepared by transient transfection with puromycin selection, and stable cell lines were established through …

Corticobasal Syndrome With Mixed Pathology In The Absence Of Grn Mutation: A Clinico-Pathological Case Of Ftld-Tdp With Coexisting Alzheimer’S And Lewy Body Pathology, Hugo Zamarron, David Irwin, Jeffery Phillips, Edward Lee, Matthew Tisdall, Corey Mcmillan

Research Colloquium

Background: Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by often asymmetric fronto-pariteal and extra-pyramidal features that is traditionally associated with tauopathy, but pathological findings are heterogenous, including other forms of frontotemporal lobar degeneration (FTLD) and mixed pathologies of aging. We present clinical, radiographic, and histopathologic features of asymmetry in a unique patient with CBS and underlying FTLD with TDP-43 pathology (FTLD-TDP), co-occurring with other age-related pathologies.

Case Presentation: A 76-year-old man presented with progressive cognitive and motor dysfunction including asymmetric parkinsonism, left-sided dystonia and rigidity, apraxia, visuospatial impairment, and a subtle social disorder including apathy and social withdrawal. The …

Integrated Mirna-Mrna Analyses Of Triple-Negative Breast Cancer In Black And White Patients With Or Without Obesity, Fokhrul Hossain, Martha I. Gonzalez-Ramirez, Jone Garai, Diana Polania-Villanueva, Li Li, Farzeen Nafees, Md Manirujjaman, Bolin Liu, Samarpan Majumder, Xiao Cheng Wu, Chindo Hicks, Luis Del Valle, Denise Danos, Augusto Ochoa, Lucio Miele, Jovanny Zabaleta

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively …