Medical Biochemistry Commons^™

The Development Of A New Water-Soluble Zinc Porphyrin, Zntpp-2mp, As A Photodynamic Therapy Agent, Emily Payne

Scholars Day Conference

Photodynamic therapy is a new technique used in cancer treatment involving the use of a photosensitizer and light exposure to kill malignant cells. This research tested the use of ZnTPP-2MP as a photosensitizer using white light as a source of possible treatment of the A549 cancer cell line, with preliminary testing on MYC-22 and other G- quadruplex DNA samples. ZnTPP-2MP was synthesized by the reaction of the porphyrin, ZnTPPC, with 2-amino-2- methyl-1-propanol. Following synthesis, the new porphyrin was purified by column chromatography using Sephadex LH-20 and G-50. To confirm the identity and structure of the product, ZnTPP-2MP was analyzed through …

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

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 …

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, …

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 (UPR^mt), 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 …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Clinicopathological And Prognostic Significance Of Cxcr4 Expression In Osteosarcoma: A Meta-Analysis, I Gusti Ngurah Ananda Wira Kusuma, Grace Yulia Alphani Yapson, John Nolan, I Gede Eka Wiratnaya, I Gede Putu Supadmanaba

BioMedicine

Background: The C-X-C Motif Chemokine Receptor (CXCR4) is an oncogene that has been widely studied and associated with worse clinicopathological features and prognosis outcomes in many types of cancer. Besides that, significance of CXCR4 expression on clinicopathological features and prognostic factors in osteosarcoma (OS) requires further validation.

Aim: We conducted a meta-analysis to evaluate the association between positive CXCR4 expression with clinicopathological features and prognosis in OS.

Methods: Literature searches on Pubmed, Cochrane Library, and Web of Science were conducted systematically up to December 2021 to find relevant references. The effects of CXCR4 expression on clinicopathological characteristics and prognostic were …

Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib

Undergraduate Student Research Internships Conference

Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …

The Effect Of Type 1 Diabetes On The Metabolic Response To Exercise, Theres Tijo

Undergraduate Student Research Internships Conference

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder that results in insufficient endogenous insulin production. Regular exercise has numerous health benefits for individuals with T1DM, however, most insulin-dependent diabetics avoid physical activity due to the fear of exercise-induced hypoglycemia (low blood glucose/BG).

The risk of hypoglycemia in this population may be partly due to lower liver glycogen stores which is a major source of blood glucose during exercise. However, the mechanism that leads to lower glycogen stores in T1DM is unknown.

The purpose of this study was to determine the effect of an acute bout of moderate-intensity aerobic exercise …

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative …

Screening Tcf19 And Kif18b To Determine Co-Regulation With Mybl1 In Triple Negative Breast Cancer Patient Tissues, Tyra Sharda Ivory

Theses (2016-Present)

The aggressive behavior in triple-negative breast cancer (TNBC) is due to genetic signaling events, which call for the comprehensive analyses of genes differentially regulated in the cancers. Our laboratory previously found that MYBL1 was over-expressed in a fraction of the TNBC, compared to some luminal, and other breast cancer subtypes. The MYBL1 gene is a proto-oncogene that serves as a strong transcriptional activator. The gene is involved in signaling events related to cell cycle signaling, differentiation, proliferation, and apoptosis, all which are differentially regulated in cancers. Because MYBL1 is a transcription regulator, involved in cancer-related mechanisms and differentially expressed in …

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …

Current Epidemiological Status And Antibiotic Resistance Profile Of Urinary Tract Infection, Muddasir Khan, Syed Hussain Shah, M. Abdullah, Muhammad Salman, Fawad Hayat, Raheela Sarwar, Neelma Hassan, Sohail Ahmad Jan, M. Saddam, Ziaur Rahman, Imran Qazi

Journal of Bioresource Management

With a longitudinal (2020–2021) completion, a set of 300 urine samples of individuals suspected of UTI was characterized based on the biochemical analysis and Kirby Bauer's disc diffusion method. Throughout, a total of 167 samples revealed UTI positivity by obtaining bacterial growth. Reporting that E. coli (69.4 %) was the most dominant when compared with Klebsiella (14.3 %), Proteus (5.9 %), S. aureus (4.7 %), P. aeruginosa (3.5 %), and Enterobacter (1.7 %), respectively. Gender-wise discrimination showed that E. coli was highly distributed among female (50.2 %) patients. A prominent percentage of E. coli (41.9 %) was found in the …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gα_s so it was long assumed that all ACs are activated by Gα_s-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …

Targeting The Cdk6 Dependence Of Ph+ Acute Lymphoblastic Leukemia, Patrizia Porazzi, Marco De Dominici, Joseph Salvino, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Ph+ ALL is a poor-prognosis leukemia subtype driven by the BCR-ABL1 oncogene, either the p190-or the p210-BCR/ABL isoform in a 70:30 ratio. Tyrosine Kinase inhibitors (TKIs) are the drugs of choice in the therapy of Ph+ ALL. In combination with standard chemotherapy, TKIs have markedly improved the outcome of Ph+ ALL, in particular if this treatment is followed by bone marrow transplantation. However, resistance to TKIs develops with high frequency, causing leukemia relapse that results in

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

MSU Graduate Theses

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …

The Effect Of Diazepam On Early Neural Stem Cells Proliferative Activity And Hippocampal-Dependent Memory After Traumatic Brain Injury, Van Khanh Doan

University Honors Theses

Traumatic brain injury (TBI) induces an upregulation of neurogenesis in the brain specifically in the hippocampus, an area pertaining to learning and memory formation. Although this upregulated response is intuitively thought to be restorative, previous studies show that the nascent neurons generated after TBI exhibit abnormalities, such as aberrant morphologies and early migrations, which could suggest to be maladaptive. The GABA-A agonist diazepam has been shown to inhibit this upregulation in neurogenesis and normalizes dendrites after TBI. To determine whether this modulation of neurogenesis is ultimately beneficial or detrimental to cognitive recovery, diazepam was administered to C57BI/6J wild-type mice following …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Polymorphisms Of Vascular Endothelial Growth Factor -2578c/A Rs699947 Are Risk Factors For Diabetic Retinopathy In Type-2 Diabetes Mellitus Patients In Bali, Indonesia, Audrey Rachel Wijaya, I Wayan Surudarma, Desak Made Wihandani, I Wayan Ardyan Sudharta Putra

BioMedicine

Background: Diabetic retinopathy (DR) is one of the complications in diabetes mellitus (DM) which caused by microvascular damage in the retina due to long term metabolic changes in diabetes. To date, there has been much research targeted on the determinant of genetic identification in DR patients. In DR, Vascular Endothelial Growth Factor (VEGF) gene is accountable for breaking down the blood-retinal barrier and implicated in the role of neovascularization. It is thought that the polymorphism of VEGF -2578C/A (rs699947) contributed to the development of diabetic retinopathy in type 2 DM.

Aim: To determine whether the polymorphisms of VEGF-2578C/A are the …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis that …

Ketogenic Diet As A Preventative Measure Or Treatment Option For Osteoarthritistargeting Nfl Athletes As A High-Risk Group, Kelsi J. Smith

Selected Honors Theses

Osteoarthritis (OA) is a prevalent joint disease that results from the degradation of articular cartilage, leading to inflammation, pain, and eventual joint failure. At one time, it was thought that OA was only the result of the natural decline experienced in old age; however, various risk factors have now been identified that may contribute to an increased risk for developing OA. Risk factors may include joint loading, altered biomechanics, obesity, and joint injury, to which athletes are exposed at a high rate. NFL athletes are one group of athletes that have continued to show a high prevalence of arthritis in …

Biological Activity And Solubility Of 5-Methoxy-1,4-Benzoquinone Having Bromoheptyl And Bromodecyl Substituents In The N-Octanol/Water System, Siti Mariyah Ulfa, Fath Dwisari, Laras Pangesti, Mohammad Farid Rahman

Makara Journal of Science

The biological activity and solubility of compounds are influenced by its chemical structure. These properties can be improved by substituting alkyl, alkoxy, and/or haloalkane in the parent skeleton. In this research, the synthesis of 3-(7-bromoheptyl)-2-methyl-5-methoxy-1,4-benzoquinone (3a) and 3-(10-bromodecyl)-2-methyl-5-methoxy-1,4-benzoquinone (3b) was achieved through the decarboxylation reaction. The solubility and biological activity of 3a and 3b were compared with that of thymoquinone (TQ), which acts as an anti-inflammatory agent. Compounds 3a and 3b were successfully synthesized and analyzed using Fourier Transform Infra-Red (FTIR) and Nuclear Magnetic Resonance (NMR). The FTIR spectrum showed the increasing intensity of …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Characterization Of Cucurbitacin-Inspired Estrone Analogues As Novel Inhibitors Of Human Atp- Binding Cassette Proteins (Abcb1 And Abcc1), Jennifer Kyeremateng

Electronic Theses and Dissertations

ATP-binding cassette (ABC) transporters are a large class of integral membrane proteins that contribute to key physiological functions in all organisms by utilizing ATP binding and hydrolysis to transport diverse substrates across membrane barriers. P-glycoprotein (P-gp/ ABCB1) and Multidrug Resistance protein 1 (MRP1/ABCC1) are widely reported ABC transporters associated with multidrug resistance in cancer. Multidrug resistance (MDR) mediated by P-gp and MRP1 is responsible for treatment failures of many metastatic cancers as a result of reduced accumulation, bioavailability and diminished potency of anticancer drugs. Currently, known P-gp and MRP1 inhibitors are limited due to toxicity, lack of selectivity and low …

Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel

Honors Projects

Building on field research in Costa Rica and Belize, this honors project analyzes environmental and endangered animal protection policies, rights, and practices in Central America and the Caribbean, and assesses the impact of veterinary science and biological research and practice, particularly conservation biology, on animal welfare concerns. Informed by the recent surge in awareness regarding zoonoses and zoonotic disease transmission, prevention and control, resulting from the current global pandemic of SARS-CoV-2, the project assesses the need for new and innovative types of collaboration, particularly involving conservation biologists, environmental scientists, public health experts, law and policy makers, and global trade and …

Design Of Hfgf1 Variant(S) With Increased Stability And Enhanced Bioactivity, Shilpi P. Agrawal

Graduate Theses and Dissertations

Fibroblast growth factors (FGFs) are involved in various cellular processes such as cell growth,proliferation, differentiation, migration, angiogenesis, wound healing and embryonic development. Human acidic fibroblast growth factor (hFGF1) binds non-selectively to all the four FGF-receptors and is therefore considered as a powerful mitogen with broadest specificity. However, pharmacological applications of hFGF1 are restricted due to the low thermal stability of the growth factor. hFGF1 has low thermodynamic stability under physiological temperatures which leads to impairment of cellular signaling process thereby preventing its potential mitogenic properties. hFGF1 has a heparin binding pocket at the C-terminus which comprises of positively charges residues. …

The Role Of Liver Sinusoidal Endothelial Cells In Liver Malady Homeostasis, Fatima Cabral

Department of Biochemistry: Dissertations, Theses, and Student Research

Current literature described techniques for the purification of liver cell types through text alone. The techniques described for the isolation of liver sinusoidal endothelial cells as well as hepatocytes described here are modified from a published article in the Journal of Visualized experiments. The video protocol allows for the user to successfully isolate cells as the most difficult parts of the procedure are demonstrated visually. The detection of liver maladies such as the non-alcoholic fatty liver disease, the stage if this disease and differentiation between non-alcoholic and alcoholic fatty liver disease is demonstrated in the development of a unique panel …