Enzymes and Coenzymes Commons^™

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …

Nrf2/Cyclooxygenase 2 Signaling In Cr(Vi)-Induced Carcinogenesis, Lei Zhao, Yi-Fang Wang, Andrea Adamcakova-Dodd, Peter Thorne, Ranakul Islam, Ke Jian Liu, Fei Chen, Jia Luo, Ling-Zhi Liu

Kimmel Cancer Center Faculty Papers

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upre- gulated in Cr(VI)-exposed lung tissues, as well as in the …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Efficacy Of Collagenase Injection In Dupuytren’S Contracture, Janson Witcher

The PA Department Journal of Medical Science

Introduction: Dupuytren's contracture is a debilitating hand condition characterized by progressive contracture of the palmar fascia. The use of collagenase clostridium histolyticum injections has emerged as a minimally invasive alternative to surgical interventions, with varying degrees of efficacy and safety compared to traditional methods like limited fasciectomy and percutaneous needle fasciotomy.

Methods: A comprehensive literature review was conducted using PubMed to assess the efficacy and safety of collagenase injections for treating Dupuytren's contracture. The search focused on peer-reviewed randomized controlled trials, systematic reviews, and meta-analyses published in the last five years. Five relevant studies were selected based on the robustness …

Identifying Notch-Regulated Genes Using A Specific Notch Signaling Inhibitor, Hammed Gafar

EWU Masters Thesis Collection

Bone remodeling is a dynamic process that requires a balance between bone resorption by osteoclasts and bone formation by osteoblasts to maintain skeletal integrity. Disruptions to this equilibrium can lead to pathological conditions such as osteoporosis. Osteoclasts originate from macrophages, and their differentiation is regulated by several signaling pathways, notably the notch signaling pathway. Gamma-secretase, an enzyme crucial for initiating notch signaling, can be inhibited by DAPT. However, DAPT also targets non-Notch substrates, complicating the identification of genes specifically regulated by Notch. To address this limitation, this study employed IMR-1A, a selective Notch pathway inhibitor that disrupts the assembly of …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Investigating The Production Challenges Of The P100.1 Phage Endolysin, Jonah O. Frago

EWU Masters Thesis Collection

Acne vulgaris is one of the most common skin diseases globally. One key aspect of acne pathogenesis is the disturbance of healthy strain diversity of the skin bacterium Cutibacterium acnes. Many acne treatments are antimicrobial; however, these treatments are generally nonspecific and carry a variety of side effects in addition to contributing to rising antibiotic resistance. Lytic bacteriophages (or phages) are viruses that infect and kill bacteria. Their lytic lifestyle is facilitated by enzymes called endolysins. Phages have been studied as an alternative to traditional antimicrobials in acne treatment and have shown reduced C. acnes load in acne lesions and …

Environmentally Persistent Free Radicals Lead To Selective Inhibition Of Cyp1 Monooxygenase Activities, And Increased Production Of Reactive Oxygen Species By Reaction Uncoupling, John Patrick Connick, Amari A. Stepter, George F. Cawley, Marilyn K. Eyer, Wayne L. Backes

School of Medicine Faculty Publications

This study focuses on the effect of Environmentally Persistent Free Radicals (EPFRs) on the P450 enzymes of the CYP1 family. EPFRs are a component of particulate pollutants, that are stable in the environment, but can generate free radicals, leading to oxidative stress and subsequent toxicity of the respiratory, cardiovascular, and immune systems once they enter an organism. The results show differences in the ability of EPFRs to inhibit CYP1-dependent substrate metabolism, with CYP1B1 being inhibited to the greatest extent. There also were differences in the ability of EPFRs to disrupt the POR•CYP1 complex, with CYP1B1 being the only form where …

Redox Control In A Fused Electron Transfer Flavoprotein From A Thermophilic Archaeon And Expanded Significance Of A Hydrogen Bond From A Conserved Histidine Residue That Contributes To Flavin Redox Tuning And Activation For Covalent Modification, Debarati Das

Theses and Dissertations--Chemistry

In absence of O₂ as terminal electron acceptors in anaerobic bacteria and archaea, carbohydrate metabolism is 15 times less efficient compared to aerobic energy metabolism resulting in energy deficit conditions. Despite their meager resources these anaerobes were able to generate H₂ and a chemiosmotic potential able to drive energy demanding reactions such as CO₂ or N₂ fixation. These observations raised concerns as production of high energy reductants (H₂) from mediocre fuels (NADH) defied the laws of thermodynamics.

In 2008, a known mechanism “electron bifurcation” but with flavins as redox mediators instead of quinones was …