Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), 2024 Wayne State University
Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), Olivia Heppell, Carlos Guerra Londono, Nilesh Gupta
Medical Student Research Symposium
Introduction: Upregulation of hypoxia-inducible factors (HIF) is an important pathological feature shared by clear cell renal cell carcinoma (ccRCC) and obstructive sleep apnea (OSA). However, it is unclear whether OSA alters the pathogenesis of ccRCC via HIF expression.
Methods: A retrospective cohort of adults undergoing nephrectomy for ccRCC was identified electronically (IRB#16040-1). The diagnosis of OSA was established with preoperative STOP-BANG scores or polysomnography. A consecutive sample of 20 individuals with and 20 without OSA was selected. Clinical characteristics and pathology results were reviewed. Resected tumor sections were immunohistochemically stained for HIF-1& HIF-2 at antibody dilutions of 1:150. Intensity and …
Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, 2024 Rowan University
Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …
Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, 2024 Thomas Jefferson University
Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu
Department of Pediatrics Faculty Papers
Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …
Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, 2023 Thomas Jefferson University
Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo
Department of Microbiology and Immunology Faculty Papers
Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state …
On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, 2023 University of Maine
On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski
Electronic Theses and Dissertations
Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …
Genetic Separation Of Brca1 Functions Reveal Mutation-Dependent Polθ Vulnerabilities, 2023 Thomas Jefferson University
Genetic Separation Of Brca1 Functions Reveal Mutation-Dependent Polθ Vulnerabilities, John J. Krais, David J. Glass, Ilse Chudoba, Yifan Wang, Wanjuan Feng, Dennis Simpson, Pooja Patel, Zemin Liu, Ryan Neumann-Domer, Robert G. Betsch, Andrea J. Bernhardy, Alice M. Bradbury, Jason Conger, Wei-Ting Yueh, Joseph Nacson, Richard T. Pomerantz, Gaorav P. Gupta, Joseph R. Testa, Neil Johnson
Department of Biochemistry and Molecular Biology Faculty Papers
Homologous recombination (HR)-deficiency induces a dependency on DNA polymerase theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for cancer therapy. BRCA1 and BRCA2 deficient cells are thought to be synthetic lethal with Polθ, but whether distinct HR gene mutations give rise to equivalent Polθ-dependence, and the events that drive lethality, are unclear. In this study, we utilized mouse models with separate Brca1 functional defects to mechanistically define Brca1-Polθ synthetic lethality. Surprisingly, homozygous Brca1 mutant, Polq−/− cells were viable, but grew slowly and had chromosomal instability. Brca1 mutant cells proficient in DNA end resection were …
Molecular Diagnostics - Biomarker Based Diagnosis Of Human Papillomavirus (Hpv), 2023 Harrisburg University of Science and Technology
Molecular Diagnostics - Biomarker Based Diagnosis Of Human Papillomavirus (Hpv), Lilly Hivner
Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity
Research on how HPV-16 E6 identifies cervical cancer more often than others.
Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6, 2023 United Arab Emirates University
Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6, Reema Saleous
Theses
Pharmacogenomics (PGx) is a relatively new field of study. It links genetics to pharmacology since it deals with the influence of the genetic makeup of the individual on their ability to respond to specific medications. Some of the most important genes in this field, dubbed very important pharmacogenes (VIPs), belong to the cytochrome P450 (CYP) superfamily of drug metabolizing enzymes. The two members of this family that are the main focus of this thesis are CYP2C19 and CYP2D6. They play major roles in the metabolism of numerous medications, and it is therefore imperative that variations within those genes in various …
Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, 2023 The Gujarat Cancer & Research Institute
Natural Remedies To Combat Aberrant Hallmark Signatures Including Altered Glycosylation In Oral Carcinoma, Kruti A. Mehta, Jayendra B. Patel, Prabhudas S. Patel
Research Symposium
Background: Tobacco associated oral cancers remain a major concern in India with higher incidence and mortality making it an Indian-centric burning issue. To combat this dreadful disease, we investigated effects of certain natural compounds on the hallmark signatures including glycosylation transcripts levels in oral carcinoma.
Methods: The tongue carcinoma cells- SAS cells were treated with tobacco compounds, natural compounds and Cisplatin. RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed to evaluate expression levels of various genes.
Results: The treatment of tobacco compounds resulted in similar pattern of altered makers (ST3GAL1, NEU3, FUT5, FUT6, MMP2, BCL2) …
Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, 2023 The University of Texas Rio Grande Valley
Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang
Research Symposium
Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …
The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., 2023 Cork Institute of Technology
The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle
International Undergraduate Journal of Health Sciences
Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …
Identification Of A Β-Arrestin-Biased Negative Allosteric Modulator For The Β2-Adrenergic Receptor, 2023 Thomas Jefferson University
Identification Of A Β-Arrestin-Biased Negative Allosteric Modulator For The Β2-Adrenergic Receptor, Michael Ippolito, Francesco De Pascali, Nathan Hopfinger, Konstantin E. Komolov, Daniela Laurinavichyute, Poli Adi Narayana Reddy, Leon A. Sakkal, Kyle Z. Rajkowski, Ajay P. Nayak, Justin Lee, Jordan Lee, Gaoyuan Cao, Preston S. Donover, Melvin Reichman, Stevens. An, Joseph M. Salvino, Raymond B. Penn, Roger S S. Armen, Charles P. Scott, Jeffrey L. Benovic
Department of Biochemistry and Molecular Biology Faculty Papers
Catecholamine-stimulated β2-adrenergic receptor (β2AR) signaling via the canonical Gs–adenylyl cyclase–cAMP–PKA pathway regulates numerous physiological functions, including the therapeutic effects of exogenous β-agonists in the treatment of airway disease. β2AR signaling is tightly regulated by GRKs and β-arrestins, which together promote β2AR desensitization and internalization as well as downstream signaling, often antithetical to the canonical pathway. Thus, the ability to bias β2AR signaling toward the Gs pathway while avoiding β-arrestin-mediated effects may provide a strategy to improve the functional consequences of β2AR activation. Since attempts to develop Gs-biased agonists and allosteric modulators for the β2AR have been largely unsuccessful, here we …
Sindrom Respons Inflamasi Sistemik, 2023 Departemen Klinik Ilmu Bedah Fakultas Kedokteran Universitas Indonesia
Sindrom Respons Inflamasi Sistemik, Yefta Moenadjat
Department of Surgery Teaching Materials and Monographs
Materi perkuliahan memuat uraian respons inflamasi pascatrauma yang berkembang menjadi sindrom respons inflamasi sistemik, berakhir dengan kegagalan organ multipel ditinjau dari aspek biomolekuler.
Buku ini merupakan bagian pertama dari seri inflamasi yang disusun dalam bentuk digital dan dipublikasi menurut konsep lisensi Commons Attribution-NonCommercial 4.0 International License untuk tujuan diseminasi.
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, 2023 TYK Medicines Inc.
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
School of Graduate Studies Faculty Publications
Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …
Increased Sirt3 Combined With Parp Inhibition Rescues Motor Function Of Sbma Mice, 2023 Thomas Jefferson University
Increased Sirt3 Combined With Parp Inhibition Rescues Motor Function Of Sbma Mice, David R. Garcia Castro, Joseph R. Mazuk, Erin M. Heine, Daniel Simpson, R. Seth Pinches, Caroline Lozzi, Kathryn Hoffman, Phillip Morrin, Dylan Mathis, Maria V. Lebedev, Elyse Nissley, Kang Hoo Han, Tyler Farmer, Diane E. Merry, Qiang Tong, Maria Pennuto, Heather L. Montie
Department of Biochemistry and Molecular Biology Faculty Papers
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity …
Advantage Of Precision Metagenomics For Urinary Tract Infection Diagnostics, 2023 Advanta Genetics
Advantage Of Precision Metagenomics For Urinary Tract Infection Diagnostics, Sadia Almas, Rob E. Carpenter, Chase Rowan, Vaibhav Tamrakar, Rahul Sharma
Human Resource Development Faculty Publications and Presentations
Background: Urinary tract infections (UTIs) remain a diagnostic challenge and often promote antibiotic overuse. Despite urine culture being the gold standard for UTI diagnosis, some uropathogens may lead to false-negative or inconclusive results. Although PCR testing is fast and highly sensitive, its diagnostic yield is limited to targeted microorganisms. Metagenomic next-generation sequencing (mNGS) is a hypothesis-free approach with potential of deciphering the urobiome. However, clinically relevant information is often buried in the enormous amount of sequencing data.
Methods: Precision metagenomics (PM) is a hybridization capture-based method with potential of enhanced discovery power and better diagnostic yield without diluting clinically relevant …
Peran Penting Inflamasom Nlrp3 Pada Aterosklerosis, 2023 Department of Histology Faculty of Medicine Universitas Indonesia
Peran Penting Inflamasom Nlrp3 Pada Aterosklerosis, Dewi Sukmawati
Jurnal Penyakit Dalam Indonesia
Cardiovascular diseases (CVDs) still contribute as the main cause of mortality and premature mortality worldwide. In Indonesia, CVDs contribute to 35% of the main cause of death in non-communicable diseases followed by diabetes at 6%. The ischemic heart disease and acute ischemic stroke is the main cause of death in Indonesia due to atherosclerosis. Atherosclerosis is a multifactorial cause, with chronic inflammation which causes myocardial infarction and acute ischemic stroke. Research demonstrated that one of the underlying mechanisms of atherosclerosis is inflammation. The current research suggested that inflammation could activate a complex of cytosol proteins, namely nucleotide-binding oligomerization domain-like receptor …
The Impact Of Essential Trace Elements On Ovarian Response And Reproductive Outcomes Following Single Euploid Embryo Transfer, 2023 Thomas Jefferson University
The Impact Of Essential Trace Elements On Ovarian Response And Reproductive Outcomes Following Single Euploid Embryo Transfer, Roberto Gonzalez-Martin, Andrea Palomar, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Estefania Conde-Vilda, Alberto J Quejido, Christine Whitehead, Richard T. Scott, Francisco Dominguez
Department of Medicine Faculty Papers
Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the …
Targeting Brd4 In The Treatment Of Pleural Fibrosis, 2023 University of Texas at Tyler
Targeting Brd4 In The Treatment Of Pleural Fibrosis, Joy Adewumi
Biotechnology Theses
Pleural fibrosis (PF) is a respiratory disorder that refers to the thickening and scarring of the pleura. Currently, there is a lack of pharmaceutic treatment options for PF. Pleural mesothelial to mesenchymal transition (MesoMT) is a critical process that contributes to the development of PF. Bromodomain-containing protein 4 (BRD4), a transcriptional and epigenetic regulator, has recently been implicated in a wide range of lung injuries. However, whether BRD4 is involved in regulating MesoMT and the development of PF remains unclear and was explored in this study. Primary human pleural mesothelial cells (HPMCs) were used to test the role of BRD4 …
Bone Growth Induction In Mucopolysaccharidosis Iva Mouse, 2023 Thomas Jefferson University
Bone Growth Induction In Mucopolysaccharidosis Iva Mouse, Estera Rintz, Angélica María Herreño-Pachón, Betul Celik, Fnu Nidhi, Shaukat Khan, Eliana Benincore-Flórez, Shunji Tomatsu
Department of Pediatrics Faculty Papers
Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting …