Biochemistry, Biophysics, and Structural Biology Commons^™

Vadadustat For Treatment Of Anemia In Patients With Dialysis-Dependent Chronic Kidney Disease Receiving Peritoneal Dialysis, Mark J Sarnak, Rajiv Agarwal, Neil Boudville, Pradip C P Chowdhury, Kai-Uwe Eckardt, Carlos R Gonzalez, Laura A Kooienga, Mark J Koury, Kwabena A Ntoso, Wenli Luo, Patrick S Parfrey, Dennis L Vargo, Wolfgang C Winkelmayer, Zhiqun Zhang, Glenn M Chertow

Faculty, Staff and Students Publications

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.

METHODS: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular …

Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Sheema Khan, Dan Ninroy, Poornima Devi Shaji, Swathi Holla, Murali M. Yallapu, Subhash C. Chauhan

Research Symposium

Introduction: Although, surgical resection and chemotherapy are the gold standard for treating Pancreatic Ductal Adenocarcinoma (PDAC), low patient survival rate remains the problem. The activating point mutation of the KRAS on codon-12 is present in 70–95% of PDAC cases and so far, no success has been achieved to inhibit KRAS. KRASG12D regulates cell proliferation, differentiation, apoptosis. Recent preliminary and published studies show high Galectin-1 (Gal-1) levels in both pancreatic cancer and stromal cells, which modulate tumor microenvironment and metastasis. Additionally, genetic deletion of gal1 inhibits metastasis and improves survival in KRAS mouse model of PDAC (1). Therefore, our objective is …

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

Determination Of Hfe C282y Mutation And Its Association With The Iron Status And Viral Load In Hiv Patients From Reynosa, Tamaulipas, Juan Carlos Hernández, Marisol Rosas Díaz, Esperanza Milagros García Oropesa, Santos Graciela Montemayor Beltrán, Juana Díaz García, Imelda Ramírez Puente

Research Symposium

Background: The HFE protein has a fundamental role in iron homeostasis, the HFE C282Y mutation prevents the specific function of the protein, causing greater intestinal absorption of iron and intracellular accumulation. The HIV virus causes a disease that attacks the cells of the immune system, mainly CD 4 T lymphocytes inducing their destruction and immunosuppression of the patient. Some viruses have the ability to disrupt cellular metabolic processes during their own replication, such is the case of HIV-1, which is involved in alteration of iron metabolism resulting in an overload of iron.

Methods: An exploratory, descriptive, cross-sectional and prolective study …

Modeling Nonsegmented Negative-Strand Rna Virus (Nnsv) Transcription With Ejective Polymerase Collisions And Biased Diffusion, Felipe-Andres Piedra

Research Symposium

Background: The textbook model of NNSV transcription predicts a gene expression gradient. However, multiple studies show non-gradient gene expression patterns or data inconsistent with a simple gradient. Regarding the latter, several studies show a dramatic decrease in gene expression over the last two genes of the respiratory syncytial virus (RSV) genome (a highly studied NNSV). The textbook model cannot explain these phenomena.

Methods: Computational models of RSV and vesicular stomatitis virus (VSV – another highly studied NNSV) transcription were written in the Python programming language using the Scientific Python Development Environment. The model code is freely available on GitHub: …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Challenges In Genetic Counseling In Hereditary Cancer Syndromes In A Mexican Oncologic Center, Diana Cristina Perez-Ibave, Diana Cristina De Lourdes Perez Ibave, María Fernanda Noriega-Iriondo, Omar Alejandro Zayas-Villanueva, Fernando Alcorta-Nuñez, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, David Hernandez-Barajas, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores

Research Symposium

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program.

Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses …

Fundamental Study Of Ionic Liquid Physicochemical Effects On Thermal Stability Of Model Biological Macromolecules, Austin Keith Clark

Theses and Dissertations

Ionic Liquids (ILs) are substances with a unique physical attribute compared to that of solid ionic salts. At room temperature, ILs are molten salts that have a variety of physical effects that can play a role in their impact on other molecules, as solvents or solutes. They can play the role of the solvent in a variety of applications, from biofuels to organic catalysis or as excipients in pharmaceutical formulations. These ILs have a desirable use as solvents due to their ability to be tunable substances. Changing the cation or anion of the IL causes a change in its physical …

Identification Of The Functional Domain Of The Dense Core Vesicle Biogenesis Factor Hid-1, Blake H. Hummer, Theodore Carter, Breanna L. Sellers, Jenna D. Triplett, Cedric S. Asensio

Biological Sciences: Faculty Scholarship

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. HID-1 is a trans-Golgi network (TGN) localized peripheral membrane protein contributing to LDCV formation. There is no information about HID-1 structure or domain architecture, and thus it remains unknown how HID-1 binds to the TGN and performs its function. We report that the N-terminus of HID-1 mediates membrane binding through a myristoyl group with a polybasic amino acid patch but lacks specificity for the TGN. In addition, we show that the C-terminus serves as the functional domain. Indeed, this isolated domain, when tethered to the TGN, …

Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield

PANDION: The Osprey Journal of Research and Ideas

Origins of life research, also known as pre-biotic chemistry or astrobiology, aims to unravel the mystery of the first cell’s origin on Earth. This interdisciplinary field encompasses biology, chemistry, and physics, with the primary goal of understanding the conditions necessary for life to emerge from abiotic environments. The RNA world hypothesis suggests that early life initially used RNA instead of DNA to store genomic information and for enzymatic functions. Protocells, membrane-bound entities with metabolic processes and self-replication capabilities, likely preceded the emergence of true cells. The challenges associated with RNA world is currently an active field of research. Advancements in …

Transgenic Mice Expressing Functional Tcrs Specific To Cardiac Myhc-Α 334–352 On Both Cd4 And Cd8 T Cells Are Resistant To The Development Of Myocarditis On C57bl/6 Genetic Background, Meghna Sur, Mahima T. Rasquinha, Rajkumar Arumugam, Chandirasegaran Massilamany, Arunkumar Gangaplara, Kiruthiga Mone, Ninaad Lasrado, Bharathi Yalaka, Aakash Doiphode, Channabasavaiah Gurumurthy, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis is a predominant cause of congestive heart failure and sudden death in children and young adolescents that can lead to dilated cardiomyopathy. Lymphocytic myocarditis mediated by T cells can result from the recognition of cardiac antigens that may involve CD4 or CD8 T cells or both. In this report, we describe the generation of T cell receptor (TCR) transgenic mice on a C57BL/6 genetic background specific to cardiac myosin heavy chain (Myhc)-α 334–352 and make the following observations: First, we verified that Myhc-α 334–352 was immunogenic in wild-type C57BL/6 mice and induced antigen-specific CD4 T cell responses despite being …

Hyaluronan Modulated Expression Of Mmps 2, 9, And 12 In Macrophages, Jeffrey S. Miller, Caitlin Howard, Steven P. Jones Phd

The Cardinal Edge

Hyaluronan (HA) is a ubiquitously expressed Glycosaminoglycan (GAG) found as a main component of the extracellular matrix (ECM). Matrix metalloproteases (MMPs) are class of enzyme responsible for the degradation of multiple ECM components, including HA. Following a myocardial infarction (MI), ECM remodeling occurs in the infarct tissue and involves an accumulation of HA. Remodeling is facilitated by multiple cell types, including macrophages. During post-MI ECM remodeling, macrophages degrade and ingulf dead cells and ECM components, a process which requires the expression of MMPs. MMPs 2, 9, and 12 are known to be elevated post-MI; MMPs 9 and 12 are known …

Mechanistic Investigations Of A Novel Braf Regulatory Switch And Braftide, An Allosteric Peptide Inhibitor Of Braf, Alison Yu

Theses and Dissertations

RAF kinases (ARAF/BRAF/CRAF or Raf-1) are serine/threonine kinases in the MAPK (RAS-RAF-MEK-ERK) pathway. The MAPK pathway is crucial in development and normal cell function. These same roles are dysregulated in cancer; BRAF is the most frequently mutated isoform in cancers and in particular, activation loop mutants BRAF V600E/K mutants have the highest mutational incidence. Three FDA approved inhibitors potently inhibit BRAF V600E/K mutants. However, these same inhibitors fail to address the non-V600E/K mutations and result in paradoxical activation of the MAPK pathway. Two strategies were employed to address the limitations of the FDA-approved inhibitors: provide novel regulatory details of RAF …

A Naturally Derived Watercress Flower-Based Phenethyl Isothiocyanate-Enriched Extract Induces The Activation Of Intrinsic Apoptosis Via Subcellular Ultrastructural And Ca2+ Efflux Alterations In An In Vitro Model Of Human Malignant Melanoma, Sotiris Kyriakou, Louiza Potamiti, Nikoletta Demosthenous, Tom Amery, Kyle Stewart, Paul G. Winyard, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

The aim of the current study was to (i) extract isolated fractions of watercress flowers enriched in polyphenols, phenethyl isothiocyanate and glucosinolates and (ii) characterize the anticancer mode of action of non-lethal, sub-lethal and lethal concentrations of the most potent extract fraction in primary (A375) and metastatic (COLO-679) melanoma cells as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Cytotoxicity was assessed via the Alamar Blue assay, whereas ultrastructural alterations in mitochondria and the endoplasmic reticulum were determined via transmission electron microscopy. Mitochondrial membrane depolarization was determined using Mito-MP dye, whereas apoptosis was evaluated through the activation of caspases-3, -8 and …

Color Stability, Physical Properties And Antifungal Effects Of Zro2 Additions To Experimental Maxillofacial Silicones: Comparisons With Tio2, Mazen Alkahtany, Mark W. Beatty, Fahd Alsalleeh, Thomas M. Petro, Bobby Simetich, You Zhou, Dennis Feely, Grigoris Polyzois

School of Veterinary and Biomedical Sciences: Faculty Publications

(1) Background: Color changes, physical degradation, and fungal infections are challenges to the longevity of maxillofacial polydimethylsiloxane (PDMS) elastomers. This study aimed to evaluate color changes, physical properties, and antifungal properties of PDMS loaded with ZrO₂ and TiO₂ submicron- and nano-sized particles. (2) Methods: A 1% weight of 40 nm or 200 nm diameter ZrO₂ or TiO₂ nanoparticles was mixed into PDMS with 2% functional intrinsic yellow pigment and polymerized. Control materials contained 13% weight 200 nm silica. Samples were exposed to 3000 h of UVB radiation (200 μW/cm²) or darkness. Color parameters L*a*b* …

Development Of Bioactive Peptidomimetics, Lei Wang

USF Tampa Graduate Theses and Dissertations

In the past two decades, a lot of different peptidomimetics, such as β-peptides, oligoureas, azapeptides, peptoids, aromatic oligoamides, and others, have been developed. These peptidomimetics with distinctive scaffolds have shown potential in protein surface recognition and mimicry, PPI regulation, catalysis, etc. Moreover, these bioactive peptidomimetics demonstrate much better bioavailability and biostability than the bioactive peptides. To expand the application of peptidomimetics, our group have developed a new sequence-specific peptidomimetics- γ-AApeptide, which is derived from chiral γ-PNA. It shows excellent advantages including highly resistant to various proteolytical degradations and has the potential to increase chemodiversity. γ-AApeptide also exhibits remarkable biomedical applications, …

Hiv-1 Vpu Protein Forms Stable Oligomers In Aqueous Solution Via Its Transmembrane Domain Self-Association, Saman Majeed, Lan Dang, Md Majharul Islam, Olamide Ishola, Peter P Borbat, Steven J Ludtke, Elka R Georgieva

Faculty, Staff and Students Publications

We report our findings on the assembly of the HIV-1 protein Vpu into soluble oligomers. Vpu is a key HIV-1 protein. It has been considered exclusively a single-pass membrane protein. Previous observations show that this protein forms stable oligomers in aqueous solution, but details about these oligomers still remain obscure. This is an interesting and rather unique observation, as the number of proteins transitioning between soluble and membrane embedded states is limited. In this study we made use of protein engineering, size exclusion chromatography, cryoEM and electron paramagnetic resonance (EPR) spectroscopy to better elucidate the nature of the soluble oligomers. …

Development Of Antiviral Peptidomimetics, Songyi Xue

USF Tampa Graduate Theses and Dissertations

Protein-protein interactions (PPIs) are essential for biological processes and are associated with a number of diseases, including cancer, infectious diseases, and neurodegenerative diseases. As a result, modulation of PPIs has been recognized as one of the most promising strategies to develop the novel drugs. Peptide modulators always exhibit higher specificity and affinities with targets than small compounds or monoclonal antibodies, but their broad medicinal effectiveness is constrained by their poor bioavailability and biostability. Peptidomimetics, which have been developed to mimic the structure as well as function of bioactive peptides and proteins, have shown excellent potential in protein surface mimicry and …

Selected Fermented Indigenous Vegetables And Fruits From Malaysia As Potential Sources Of Natural Probiotics For Improving Gut Health, Olaide Olawunmi Ajibola, Raymond Thomas, Babatunde Femi Bakare

Biochemistry Publications

In the Peninsular Malaysia and Northern Borneo island of Malaysia, various rich indigenous leafy vegetables and fruits grow and contribute to the nutritional and dietary values of the population. They have high water contents, thus, naturally vulnerable to rapid food spoilage. Food preservation and processing play a vital role in the inhibition of food pathogens in fruits and vegetables that are prevalent in Malaysia. Lactic acid fermentation is generally a local-based bioprocess, among the oldest form and well-known for food-processing techniques among indigenous people there. The long shelf life of fermented vegetables and fruits improves their nutritional values and antioxidant …

Molecular Mechanisms Regulating Prometaphase And Metaphase States For Faithful Chromosome Segregation, Sarah Yvette Valles

Dartmouth College Ph.D Dissertations

Cells progress through different stages of the cell cycle as they ultimately prepare to divide during mitosis. Mitosis relies on many interconnected networks to carry out the coordinated events required for faithful chromosome segregation. When a cell enters mitosis, chromosomes are highly condensed and sister chromatids are held together by cohesion. Kinetochores assemble at the constricted regions on each chromosome. The kinetochore is a large macromolecular structure composed of many proteins that form the binding site for microtubules of the mitotic spindle to attach. These kinetochore-microtubule (k-MT) attachments serve to align chromosomes at the center of the cell and are …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

A Novel Grk3-Hdac2 Regulatory Pathway Is A Key Direct Link Between Neuroendocrine Differentiation And Angiogenesis In Prostate Cancer Progression, Samira Naderinezhad, Guoliang Zhang, Zheng Wang, Dayong Zheng, Mohit Hulsurkar, Michael Bakhoum, Ning Su, Han Yang, Tao Shen, Wenliang Li

Faculty, Staff and Students Publications

The mechanisms underlying the progression of prostate cancer (PCa) to neuroendocrine prostate cancer (NEPC), an aggressive PCa variant, are largely unclear. Two prominent NEPC phenotypes are elevated NE marker expression and heightened angiogenesis. Identifying the still elusive direct molecular links connecting angiogenesis and neuroendocrine differentiation (NED) is crucial for our understanding and targeting of NEPC. Here we found that histone deacetylase 2 (HDAC2), whose role in NEPC has not been reported, is one of the most upregulated epigenetic regulators in NEPC. HDAC2 promotes both NED and angiogenesis. G protein-coupled receptor kinase 3 (GRK3), also upregulated in NEPC, is a critical …

Bacteroides Fragilis In The Gut Microbiomes Of Alzheimer’S Disease Activates Microglia And Triggers Pathogenesis In Neuronal C/Ebpβ Transgenic Mice, Yiyuan Xia, Yifan Xiao, Zi-Hao Wang, Ashfaqul M. Alam, John P. Haran, Beth A. Mccormick, Xiji Shu, Xiaochuan Wang, Keqiang Ye

Markey Cancer Center Faculty Publications

Gut dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPβ transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPβ transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPβ/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors’ fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing …

Syne1 Mutation Is Associated With Increased Tumor Mutation Burden And Immune Cell Infiltration In Ovarian Cancer, Laura M. Harbin, Nan Lin, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer …

Unleashing The Potential Of 1,3-Diketone Analogues As Selective Lh2 Inhibitors, Juhoon Lee, Hou-Fu Guo, Shike Wang, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Zhifeng Jing, Rae M. Sammons, Eun Jeong Cho, Pengyu Ren, G. Andrés Cisneros, Jonathan M. Kurie, Kevin N. Dalby

Markey Cancer Center Faculty Publications

Lysyl hydroxylase 2 (LH2) catalyzes the formation of highly stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus promoting lung cancer metastasis through its capacity to modulate specific types of collagen cross-links within the tumor stroma. Using 1 and 2 from our previous high-throughput screening (HTS) as lead probes, we prepared a series of 1,3-diketone analogues, 1−18, and identified 12 and 13 that inhibit LH2 with IC50’s of approximately 300 and 500 nM, respectively. Compounds 12 and 13 demonstrate selectivity for LH2 over LH1 and LH3. Quantum mechanics/molecular mechanics (QM/MM) modeling indicates that the selectivity of 12 and 13 may stem from …

Nurse Leader Perceptions Of Data In The Veterans Health Administration: A Qualitative Evaluation, Janine J Wong, Richard P Sorelle, Christine Yang, Melissa K Knox, Sylvia J Hysong, Lynette E Dorsey, Patrick N O'Mahen, Laura A Petersen

Faculty, Staff and Students Publications

Healthcare systems and nursing leaders aim to make evidence-based nurse staffing decisions. Understanding how nurses use and perceive available data to support safe staffing can strengthen learning healthcare systems and support evidence-based practice, particularly given emerging data availability and specific nursing challenges in data usability. However, current literature offers sparse insight into the nature of data use and challenges in the inpatient nurse staffing management context. We aimed to investigate how nurse leaders experience using data to guide their inpatient staffing management decisions in the Veterans Health Administration, the largest integrated healthcare system in the United States. We conducted semistructured …

Oral Delivery Of Rnai For Cancer Therapy, Humayra Afrin, Renu Geetha Bai, Raj Kumar, Sheikh Shafin Ahmad, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very …

Factors Influencing Prescribing The First Add-On Disease-Modifying Antirheumatic Drugs In Patients Initiating Methotrexate For Rheumatoid Arthritis, Yinan Huang, Satabdi Chatterjee, Sandeep K Agarwal, Hua Chen, Michael L Johnson, Rajender R Aparasu

Faculty, Staff and Students Publications

BACKGROUND: Advances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX.

METHODS: This retrospective cohort study utilized the MarketScan data (2012-2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with …

The Transcription Factor Chrebp Links Mitochondrial Lipidomes To Mitochondrial Morphology And Progression Of Diabetic Kidney Disease, Li Li, Jianyin Long, Koki Mise, Naravat Poungavrin, Philip L Lorenzi, Iqbal Mahmud, Lin Tan, Pradip K Saha, Yashpal S Kanwar, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

A substantial body of evidence has established the contributions of both mitochondrial dynamics and lipid metabolism to the pathogenesis of diabetic kidney disease (DKD). However, the precise interplay between these two key metabolic regulators of DKD is not fully understood. Here, we uncover a link between mitochondrial dynamics and lipid metabolism by investigating the role of carbohydrate-response element-binding protein (ChREBP), a glucose-responsive transcription factor and a master regulator of lipogenesis, in kidney podocytes. We find that inducible podocyte-specific knockdown of ChREBP in diabetic db/db mice improves key biochemical and histological features of DKD in addition to significantly reducing mitochondrial fragmentation. …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …