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Full-Text Articles in Medical Biochemistry

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi Mar 2024

Unraveling Sorafenib Resistance In Hepatocellular Carcinoma: Exploring Key Facets, Dennis Kwabiah, Kyle Doxtater, Yamile Abuchard, Sophia Leslie, Ricardo Pequeno Bracho, Shaibir Hussain, Manish K. Tripathi

Research Symposium

Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated …


The Effects Of Curcumin On Erα, P53, And P21 In The Mcf-7 Breast Cancer Cell Line, Samantha E. Pfiffner, Mia Morse, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D. Mar 2024

The Effects Of Curcumin On Erα, P53, And P21 In The Mcf-7 Breast Cancer Cell Line, Samantha E. Pfiffner, Mia Morse, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D.

Medical Student Research Symposium

Curcumin is a golden-yellow flavonoid compound derived from the turmeric plant root that has been used in Chinese and Indian medicine for centuries. Curcumin has been shown to have antioxidant and anti-inflammatory properties, and because of this, has been gaining traction in the field of cancer research. Breast cancer is the most commonly diagnosed cancer in women, and is the second leading cause of cancer death in women, next to lung cancer. Because of the prevalence and mortality of breast cancer, possible therapeutics must be investigated. Due to the beneficial properties of curcumin and pervasiveness of breast cancer, we have …


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 Mar 2024

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 …


Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie Jan 2024

Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie

School of Medicine Faculty Publications

Background; Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. Methods; The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and …


Jak2 And Ptprc Mrna Expression Levels In Ankylosing Spondylitis And Systemic Lupus Erythematosus Patients, Yasser As El Ghobashy, Ibrahim Elmadbouh, Dina Salem Fotoh, Enas Subhi Zahran, Asmaa Mahmoud Shukry, Sherin Sobhy El Naidany Jan 2024

Jak2 And Ptprc Mrna Expression Levels In Ankylosing Spondylitis And Systemic Lupus Erythematosus Patients, Yasser As El Ghobashy, Ibrahim Elmadbouh, Dina Salem Fotoh, Enas Subhi Zahran, Asmaa Mahmoud Shukry, Sherin Sobhy El Naidany

Menoufia Medical Journal

Objectives: to evaluate RNA expression levels of Janus Kinase 2 (JAK 2) and protein tyrosine phosphatase receptor type C (PTPRC) genes in SLE and AS and correlate them with the severity of the two diseases. Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of clinical symptoms. Ankylosing spondylitis (AS) is an autoimmune inflammatory disease of young adult, affecting the axial skeleton and articular joints. Methods: A case-control study included 96 subjects: (32 SLE patients, 32 AS patients, and 32 healthy control subjects). Differences in the expression levels of JAK2 and PTPRC in the blood of …


On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski Dec 2023

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 …


Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser Dec 2023

Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Human sirtuin isoform 2 (SIRT2) is an NAD+-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking. Dimerized SIRT2 dissociates into monomers upon binding long fatty acylated substrates (decanoyl-, dodecanoyl-, and myristoyl-lysine). However, we did not observe dissociation of dimeric SIRT2 in the presence of acetyl-lysine. Analysis of X-ray crystal structures led us to discover a SIRT2 double mutant (Q142A/E340A) that …


“Cost-Effective Markers To Identify Metabolically Healthy/Unhealthy Individuals And Their Future Risk For Cardiovascular Disorders”, Shobha C Ramachandra, Akila Prashant, Akshitha Shivanna, Ananth Koushik Bhujanga, Syeda Meherunnisa, Prashant Vishwanath Nov 2023

“Cost-Effective Markers To Identify Metabolically Healthy/Unhealthy Individuals And Their Future Risk For Cardiovascular Disorders”, Shobha C Ramachandra, Akila Prashant, Akshitha Shivanna, Ananth Koushik Bhujanga, Syeda Meherunnisa, Prashant Vishwanath

International Journal of Health and Allied Sciences

Background: With the rising prevalence of metabolically healthy obese, it becomes essential to identify markers to differentiate them from metabolically unhealthy obese and their future risk for cardiovascular disorders (CVD). The study aims to identify suitable markers for risk stratification of metabolically healthy/unhealthy individuals and their risk for CVD. Method: Total 84 individuals aged 18-60 years of age without any comorbidities were enrolled. Their demographic details along with anthropometric measurements were noted. The biochemical parameters like fasting glucose, insulin, lipid profile, and serum adipokines were estimated. Insulin resistance (IR) markers and atherogenic indices were calculated. The data were analyzed on …


On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato Oct 2023

On A Sugar High: Role Of O-Glcnacylation In Cancer, Giang Le Minh, Emily M. Esquea, Riley G. Young, Jessie Huang, Mauricio J. Reginato

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Recent advances in the understanding of the molecular mechanisms underlying cancer progression have led to the development of novel therapeutic targeting strategies. Aberrant glycosylation patterns and their implication in cancer have gained increasing attention as potential targets due to the critical role of glycosylation in regulating tumor-specific pathways that contribute to cancer cell survival, proliferation, and progression. A special type of glycosylation that has been gaining momentum in cancer research is the modification of nuclear, cytoplasmic, and mitochondrial proteins, termed O-GlcNAcylation. This protein modification is catalyzed by an enzyme called O-GlcNAc transferase (OGT), which uses the final product of the …


Novel Therapy Targeting Mutant-Krasg12d And Galectin-1 In Pancreatic Cancer, Ana I. Martinez Bulnes, Nirnoy Dan, Poornima Devi Shaji, Swathi Holla, Murali M. Yallapu, Sheema Khan Oct 2023

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

Research Colloquium

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 …


Molecular And Biochemical Analysis Of Cytochrome P450 2c19 And 2d6, Reema Saleous Oct 2023

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 …


Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio Sep 2023

Oral Dosages Of The Nsaid Aspirin Decreased The Growth Rate Of Species Found In The Human Gut Microbiome Including Akkermansia Muciniphila, Bacteroides Fragilis, Clostridium Sordellii, And Clostridium Difficile, Wyatt H. Greenbaum, Garrett J. Greenbaum, Anna Spiezio

PANDION: The Osprey Journal of Research and Ideas

Over past few decades, new insight has been revealed in the scientific community about the importance of the human gut microbiome relating to general health. It is known that imbalances in the species that reside in the human gut can cause organism-wide problems in humans. When prescribing or injecting oral medications, the thought of the downstream effects on the gut microbiome are not always considered. By exposing known healthy members of the gut; Akkermansia muciniphila, Bacteroides fragilis, Clostridium sordellii, and Clostridium difficile to the Aspirin, this study attempted to provide insight into the effects of the drug on bacterial growth. …


Evaluation Of Oxidative Status, Potassium, Magnesium, And Lipid Profile In Serum Of Patients With Β-Thalassemia Major, Thi-Qar, Iraq., Ahmed Jaber Ibrahim, Arwa H. M. Al–Saeed Sep 2023

Evaluation Of Oxidative Status, Potassium, Magnesium, And Lipid Profile In Serum Of Patients With Β-Thalassemia Major, Thi-Qar, Iraq., Ahmed Jaber Ibrahim, Arwa H. M. Al–Saeed

Maaen Journal for Medical Sciences

Beta thalassemia major () is one of the more prevalent hereditary diseases in the globe due to a deficiency of globin chains. It is associated with lipid abnormalities, electrolytes, and oxidative stress that can lead to potentially fatal complications. The current study included 100 patients diagnosed with in an age group of 2-18 years compared to 80 healthy subjects. The current study included evaluating Complete blood count (CBC), iron status, lipid profile, potassium, and magnesium. Also, Oxidative status represented by Superoxide dismutase (SOD), Catalase (CAT), and Nitric oxide (NO) were investigated. The finding of this study included a significant increase …


Development Of A Sensitive Microplate Assay For Characterizing Rna Methyltransferase Activity: Implications For Epitranscriptomics And Drug Development, Isaiah K. Mensah, Allison B. Norvil, Ming He, Emma Lendy, Nicole Hjortland, Hern Tan, Richard T. Pomerantz, Andrew Mesecar, Humaira Gowher Sep 2023

Development Of A Sensitive Microplate Assay For Characterizing Rna Methyltransferase Activity: Implications For Epitranscriptomics And Drug Development, Isaiah K. Mensah, Allison B. Norvil, Ming He, Emma Lendy, Nicole Hjortland, Hern Tan, Richard T. Pomerantz, Andrew Mesecar, Humaira Gowher

Department of Biochemistry and Molecular Biology Faculty Papers

RNA methylation is a ubiquitous post-transcriptional modification found in diverse RNA classes and is a critical regulator of gene expression. In this study, we used Zika virus RNA methyltransferase (MTase) to develop a highly sensitive microplate assay that uses a biotinylated RNA substrate and radiolabeled AdoMet coenzyme. The assay is fast, highly reproducible, exhibits linear progress-curve kinetics under multiple turnover conditions, has high sensitivity in competitive inhibition assays, and significantly lower background levels compared with the currently used method. Using our newly developed microplate assay, we observed no significant difference in the catalytic constants of the full-length nonstructural protein 5 …


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 Sep 2023

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, …


Fan1 Removes Triplet Repeat Extrusions Via A Pcna- And Rfc-Dependent Mechanism, Ashutosh S. Phadte, Mayuri Bhatia, Hope Ebert, Haaris Abdullah, Essam Abed Elrazaq, Konstantin E. Komolov, Anna Pluciennik Aug 2023

Fan1 Removes Triplet Repeat Extrusions Via A Pcna- And Rfc-Dependent Mechanism, Ashutosh S. Phadte, Mayuri Bhatia, Hope Ebert, Haaris Abdullah, Essam Abed Elrazaq, Konstantin E. Komolov, Anna Pluciennik

Department of Biochemistry and Molecular Biology Faculty Papers

Human genome-wide association studies have identified FAN1 and several DNA mismatch repair (MMR) genes as modifiers of Huntington’s disease age of onset. In animal models, FAN1 prevents somatic expansion of CAG triplet repeats, whereas MMR proteins promote this process. To understand the molecular basis of these opposing effects, we evaluated FAN1 nuclease function on DNA extrahelical extrusions that represent key intermediates in triplet repeat expansion. Here, we describe a strand-directed, extrusion-provoked nuclease function of FAN1 that is activated by RFC, PCNA, and ATP at physiological ionic strength. Activation of FAN1 in this manner results in DNA cleavage in the vicinity …


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 Jul 2023

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 …


Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …


Changes In Nascent Chromatin Structure Regulate Activation Of The Pro-Fibrotic Transcriptome And Myofibroblast Emergence In Organ Fibrosis, Morgan D. Basta, Svetlana Petruk, Ross Summer, Joel Rosenbloom, Peter J. Wermuth, Edward J. Macarak, Alex V. Levin, Alexander Mazo, Janice L. Walker May 2023

Changes In Nascent Chromatin Structure Regulate Activation Of The Pro-Fibrotic Transcriptome And Myofibroblast Emergence In Organ Fibrosis, Morgan D. Basta, Svetlana Petruk, Ross Summer, Joel Rosenbloom, Peter J. Wermuth, Edward J. Macarak, Alex V. Levin, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. …


A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam May 2023

A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam

SKMC Student Presentations and Publications

SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a 'decoy' to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range …


Cardiac Biomarkers Differentiate Kawasaki Disease From Multisystem Inflammatory Syndrome In Children Associated With Covid-19, Mollie Walton May 2023

Cardiac Biomarkers Differentiate Kawasaki Disease From Multisystem Inflammatory Syndrome In Children Associated With Covid-19, Mollie Walton

Research Days

Background: Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show considerable clinical overlap. The goal of this study was to determine if cardiac biomarkers can differentiate KD from MIS-C.

Objectives/Goal: The goal of this study was to determine if cardiac biomarkers differentiate KD from MIS-C.

Methods/Design: The International Kawasaki Disease Registry enrolled (n=2903) contemporaneous KD and MIS-C patients1st, 2020, through June 30th, 2022. The study population was confined to KD patients meeting American Heart Association KD criteria with no prior COVID-19 infection and MIS-C patients meeting Centers for Disease Control and Prevention criteria with confirmed …


The Correlation Between Serum C-Reactive Protein Level And Risk Of Future Cardiovascular Disease: A Neurodivergent Population Dilemma, Brandon Cunha, Andrea Iannuzzelli, Venkateswar Venkataraman May 2023

The Correlation Between Serum C-Reactive Protein Level And Risk Of Future Cardiovascular Disease: A Neurodivergent Population Dilemma, Brandon Cunha, Andrea Iannuzzelli, Venkateswar Venkataraman

Rowan-Virtua Research Day

Extensive research on neurotypical (NT) populations has demonstrated that a chronically elevated level of serum C Reactive Protein (CRP) is a strong predictor of future cardiovascular disease (CVD). Interestingly, many neurodivergent (ND) populations experience chronically elevated CRP levels higher than NT controls. Current research is concerned with establishing the significance of this relationship to accurately predict CVD risk for potentially at risk ND patients. To contribute to this gap in knowledge, the Rowan-Virtua Regional Integrated Special Needs (RISN) Center patient population will be studied to identify trends in baseline serum CRP levels across a multitude of ND conditions. A clinical …


Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper May 2023

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …


Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters May 2023

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD+) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD+ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPRmt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD+ and through increasing levels …


An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba May 2023

An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba

Chemistry & Biochemistry Undergraduate Honors Theses

Hemagglutinin is a protein on the surface of Human Influenza Viruses.1 It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.4 In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.4 These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and …


Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications, Kezia Reji Thomas May 2023

Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications, Kezia Reji Thomas

Senior Honors Theses

Peripherally selective compounds have been found to stimulate endocannabinoid receptor activity, which has been observed to have positive physiological effects such as ocular wound healing and inflammation control. The activation of the cannabinoid 1 receptor via binding of the endogenous ligands, anandamide and 2-arachidonoylglycerol, has been indicated to elicit these effects. Both ligands are controlled by two hydrolase enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which can be targeted for therapeutic inhibition. Sulfonamide derivatives of JZL195 containing carbamate functionalities in the southern region of the inhibitor compounds were produced using novel carbamate exchange reactions. Polar functionalities were …


Candidate Variants In Dna Replication And Repair Genes In Early-Onset Renal Cell Carcinoma Patients Referred For Germline Testing, Elena V. Demidova, Ilya G. Serebriiskii, Ramilia Vlasenkova, Simon Kelow, Mark D. Andrake, Tiffiney R. Hartman, Tatiana Kent, James Virtucio, Gail L. Rosen, Richard T. Pomerantz, Roland L. Dunbrack, Erica A. Golemis, Michael J. Hall, David Y.T. Chen, Mary B. Daly, Sanjeevani Arora Apr 2023

Candidate Variants In Dna Replication And Repair Genes In Early-Onset Renal Cell Carcinoma Patients Referred For Germline Testing, Elena V. Demidova, Ilya G. Serebriiskii, Ramilia Vlasenkova, Simon Kelow, Mark D. Andrake, Tiffiney R. Hartman, Tatiana Kent, James Virtucio, Gail L. Rosen, Richard T. Pomerantz, Roland L. Dunbrack, Erica A. Golemis, Michael J. Hall, David Y.T. Chen, Mary B. Daly, Sanjeevani Arora

Department of Biochemistry and Molecular Biology Faculty Papers

Background: Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined.

Methods: Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes.

Results: Analysis of whole-exome sequencing (WES) data found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of …


Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner Apr 2023

Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6–6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to …


Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo Apr 2023

Biophysical Changes Of Leukocyte Activation (And Netosis) In The Cellular Host Response To Sepsis, Matt G. Sorrells, Yurim Seo, Melia Magnen, Bliss Broussard, Roya Sheybani, Ajay M. Shah, Hollis R. O’Neal, Henry T.K. Tse, Mark R. Looney, Dino Di Carlo

School of Medicine Faculty Publications

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a …


Facile Green Synthesis Of Cinnamomum Tamala Extract Capped Silver Nanoparticles And Its Biological Applications, Sajina Narath, S. Sharath Shankar, Saranya Kothaplamoottil Sivan, Bini George, T. Dennis Thomas, Sankarannair Sabarinath, Sajithkumar K. Jayaprakash, Stanisław Wacławek, Vinod V.T. Padil Apr 2023

Facile Green Synthesis Of Cinnamomum Tamala Extract Capped Silver Nanoparticles And Its Biological Applications, Sajina Narath, S. Sharath Shankar, Saranya Kothaplamoottil Sivan, Bini George, T. Dennis Thomas, Sankarannair Sabarinath, Sajithkumar K. Jayaprakash, Stanisław Wacławek, Vinod V.T. Padil

Department of Medicine Faculty Papers

The plant mediated biogenic synthesis of nanoparticles is of magnificent concern due to its eco-benign and single pot nature. Here, Cinnamomum tamala (C. tamala) aqueous leaf extract was utilised for the silver nanoparticles’ (Ag NPs) synthesis. The phytoconstituents in the leaf extract were analysed by standard methods. These metabolites, especially carbohydrate polymers reduce Ag ions to Ag NPs accompanied by a reddish-brown coloration of the reaction mixture. The visual observation of intense brown colour is the first indication of the formation of Ag NPs. Various spectro-analytical techniques further characterise the Ag NPs. The green synthesised spherical Ag NPs were crystalline …