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Amino Acids, Peptides, and Proteins

2022

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Full-Text Articles in Medicine and Health Sciences

Structure-Based Rational Design Of Small Α-Helical Peptides With Broad-Spectrum Activity Against Multidrug-Resistant Pathogens, Sandeep Lohan, Anastasia G. Konshina, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang Dec 2022

Structure-Based Rational Design Of Small Α-Helical Peptides With Broad-Spectrum Activity Against Multidrug-Resistant Pathogens, Sandeep Lohan, Anastasia G. Konshina, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of small (7–12 mer) amphipathic cationic peptides were designed and synthesized to create short helical peptides with broad-range bactericidal activity and selectivity toward the bacterial cells. The analysis identified a lead 12-mer peptide 8b with broad-spectrum activity against Gram-positive (MIC = 3.1–6.2 μg/mL) and Gram-negative (MIC = 6.2–12.5 μg/mL) bacteria and selectivity toward prokaryotic versus eukaryotic cells (HC50 = 280 μg/mL, >75% cell viability at 150 μg/mL). The rapid membranolytic action of 8b was demonstrated by a calcein dye leakage assay and confirmed using scanning electron microscopy. According to circular dichroism and NMR spectroscopy, the peptides have an …


Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …


Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez Dec 2022

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …


Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore Dec 2022

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …


Identification Of The Type Eleven Secretion System (T11ss) And Characterization Of T11ss-Dependent Effector Proteins, Alex S. Grossman Dec 2022

Identification Of The Type Eleven Secretion System (T11ss) And Characterization Of T11ss-Dependent Effector Proteins, Alex S. Grossman

Doctoral Dissertations

Host-associated microbes live in dangerous environments as a result of host immune killing, nutrient provisioning, and physiological conditions. Bacteria have evolved a host of surface and secreted proteins to help interact with this host environment and overcome nutrient limitation. The studies included within this dissertation describe the identification of a novel bacterial secretion system which has evolved to transport these symbiosis mediating proteins. This system, termed the type eleven secretion system (T11SS), is present throughout the Gram negative phylum Proteobacteria, including many human pathogens such as Neisseria meningitidis, Acinetobacter baumanii, Haemophilus haemolyticus, and Proteus vulgaris. Furthermore, …


Oxidative Stress Strongly Restricts The Effect Of Codon Choice On The Efficiency Of Protein Synthesis In Escherichia Coli, Lorenzo Eugenio Leiva, Sara Elgamal, Sebastian A. Leidel, Omar Orellana, Michael Ibba, Assaf Katz Nov 2022

Oxidative Stress Strongly Restricts The Effect Of Codon Choice On The Efficiency Of Protein Synthesis In Escherichia Coli, Lorenzo Eugenio Leiva, Sara Elgamal, Sebastian A. Leidel, Omar Orellana, Michael Ibba, Assaf Katz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Introduction

The response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition.

Methods

In order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons.

Results

Using these reporters, we observed that …


Membrane-Active Cyclic Amphiphilic Peptides: Broad-Spectrum Antibacterial Activity Alone And In Combination With Antibiotics, Eman H. M. Mohammed, Sandeep Lohan, Tarra Ghaffari, Shilpi Gupta, Rakesh K. Tiwari, Keykavous Parang Nov 2022

Membrane-Active Cyclic Amphiphilic Peptides: Broad-Spectrum Antibacterial Activity Alone And In Combination With Antibiotics, Eman H. M. Mohammed, Sandeep Lohan, Tarra Ghaffari, Shilpi Gupta, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We designed a library of 24 cyclic peptides containing arginine (R) and tryptophan (W) residues in a sequential manner [RnWn] (n = 2–7) to study the impact of the hydrophilic/hydrophobic ratio, charge, and ring size on the antibacterial activity against Gram-positive and Gram-negative strains. Among peptides, 5a and 6a demonstrated the highest antimicrobial activity. In combination with 11 commercially available antibiotics, 5a and 6a showed remarkable synergism against a large panel of resistant pathogens. Hemolysis (HC50 = 340 μg/mL) and cell viability against mammalian cells demonstrated the selective lethal action of 5a against bacteria over …


The Glycemic, Cholesterol, And Weight Effects Of L-Carnitine In Diabetes: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Jennifer Ko, Eva Y. Wong, Huyentran N. Tran, Rebecca J.C. Tran, Diana X. Cao Nov 2022

The Glycemic, Cholesterol, And Weight Effects Of L-Carnitine In Diabetes: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Jennifer Ko, Eva Y. Wong, Huyentran N. Tran, Rebecca J.C. Tran, Diana X. Cao

Pharmacy Faculty Articles and Research

Introduction

L-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood.

Methods

A systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model.

Results

Seventeen studies …


Protein Phosphatase 2a Regulates Xanthine Oxidase-Derived Ros Production In Macrophages And Influx Of Inflammatory Monocytes In A Murine Gout Model, Sandy Elsayed, Khaled A. Elsaid Nov 2022

Protein Phosphatase 2a Regulates Xanthine Oxidase-Derived Ros Production In Macrophages And Influx Of Inflammatory Monocytes In A Murine Gout Model, Sandy Elsayed, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Gout is a common arthritis, due to deposition of monosodium urate (MSU) crystals which results in IL-1β secretion by tissue-resident macrophages. Xanthine oxidase (XO) catalyzes uric acid (UA) production and in the process, reactive oxygen species (ROS) are generated which contributes to NLRP3 inflammasome activation. Protein phosphatase 2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. The objective of this study was to investigate whether PP2A regulates gout inflammation, mediated by XO activity modulation. We studied UA and ROS generations in MSU stimulated murine bone marrow derived macrophages (BMDMs) in response to fingolimod phosphate, a PP2A activator, …


Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar Nov 2022

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …


Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq Oct 2022

Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Community Health Sciences

Background: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan.
Material and methods: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food …


Identification And Characterization Of Epicuticular Proteins Of Nematodes Sharing Motifs With Cuticular Proteins Of Arthropods, Bruno Betschart, Marco Bisoffi, Ferial Alaeddine Oct 2022

Identification And Characterization Of Epicuticular Proteins Of Nematodes Sharing Motifs With Cuticular Proteins Of Arthropods, Bruno Betschart, Marco Bisoffi, Ferial Alaeddine

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Specific collagens and insoluble proteins called cuticlins are major constituents of the nematode cuticles. The epicuticle, which forms the outermost electron-dense layer of the cuticle, is composed of another category of insoluble proteins called epicuticlins. It is distinct from the insoluble cuticlins localized in the cortical layer and the fibrous ribbon underneath lateral alae. Our objective was to identify and characterize genes and their encoded proteins forming the epicuticle. The combination between previously obtained laboratory results and recently made available data through the whole-genome shotgun contigs (WGS) and the transcriptome Shotgun Assembly (TSA) sequencing projects of Ascaris suum allowed us …


Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan Oct 2022

Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan

Doctoral Dissertations

Biomaterials are widely applied for the diagnosis and treatment of numerous diseases. In addition to fulfilling specific biological functions, biomaterials must also be non-toxic, biocompatible, and sterilizable to be regarded as safe-for-use. Polymers are excellent candidates for fabricating functional biomaterials due to their wide availability and varied properties and may be natural or synthetic. Polymer precursors are fabricated into coatings, foams, scaffolds, gels, composites, and nanomaterials for several biomedical applications. This dissertation focuses on two types of polymeric biomaterials – protein-based materials and synthetic polymeric nanoparticles. Proteins are biopolymers that naturally occur with a variety of structural and functional properties. …


Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter Oct 2022

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …


Interpretable Machine Learning Models For Molecular Design Of Tyrosine Kinase Inhibitors Using Variational Autoencoders And Perturbation-Based Approach Of Chemical Space Exploration, Keerthi Krishnan, Ryan Kassab, Steve Agajanian, Gennady M. Verkhivker Sep 2022

Interpretable Machine Learning Models For Molecular Design Of Tyrosine Kinase Inhibitors Using Variational Autoencoders And Perturbation-Based Approach Of Chemical Space Exploration, Keerthi Krishnan, Ryan Kassab, Steve Agajanian, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, we introduce an integrative machine learning strategy for the autonomous molecular design of protein kinase inhibitors using variational autoencoders and a novel cluster-based perturbation approach for exploration of the chemical latent space. The proposed strategy combines autoencoder-based embedding of small molecules with a cluster-based perturbation approach for efficient navigation of the latent space and a feature-based kinase inhibition likelihood classifier that guides optimization of the molecular properties and targeted molecular design. In the proposed generative approach, molecules sharing similar structures tend to cluster in the latent space, and interpolating between two molecules in the latent space …


Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward Sep 2022

Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward

Doctoral Dissertations

Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …


Protein-Protein Interaction Prediction From Language Of Biological Coding, Nayan Howladar Aug 2022

Protein-Protein Interaction Prediction From Language Of Biological Coding, Nayan Howladar

University of New Orleans Theses and Dissertations

Protein-protein interactions in a cell are essential to the characterization and performance of various fundamental biological processes. Due to the tedious, resource-expensive, and time-consuming experimental processes, computational techniques to solve protein pair interaction difficulties have emerged as an active research area in bioinformatics. This research seeks to develop an innovative machine learning-based technique that predicts the interaction of a protein pair based on carefully selected input features and exploits information-rich evolutionary information. We developed a protein-protein interaction predictor, PPILS, that leverages the evolutionary knowledge from the protein language model. We examined several distinct neural network architectures: CNN+LSTM, Transformer, Encoder-Decoder, and …


Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan Aug 2022

Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan

Medical College Documents

No abstract provided.


In-Silico Analysis Of Interacting Pathways Through Kim-1 Protein Interaction In Diabetic Nephropathy, Fatima Abid, Z Rubab, Syeda Sadia Fatima, A Qureshi, Arfa Azhar, A Jafri Jul 2022

In-Silico Analysis Of Interacting Pathways Through Kim-1 Protein Interaction In Diabetic Nephropathy, Fatima Abid, Z Rubab, Syeda Sadia Fatima, A Qureshi, Arfa Azhar, A Jafri

Department of Biological & Biomedical Sciences

Background: Human Kidney Injury Molecule-1, also known as HAVCR-1 (Hepatitis A virus cellular receptor 1), belongs to the cell-surface protein of immunoglobulin superfamily involved in the phagocytosis by acting as scavenger receptor epithelial cells. The study focused on pinpointing the mechanisms and genes that interact with KIM-1.
Methods: This in-silico study was done from March 2019 to December 2019. The Enrichment and protein-protein interaction (PPI) network carefully choose proteins. In addition, the diagramed gene data sets were accomplished using FunRich version 3.1.3. It was done to unveil the proteins that may affect the regulation of HAVCR1 or may be regulated …


Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang Jul 2022

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …


Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan Jul 2022

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …


Emicizumab-Kxwh: A Critical Review, Kiera O'Leary Jun 2022

Emicizumab-Kxwh: A Critical Review, Kiera O'Leary

International Undergraduate Journal of Health Sciences

The first descriptions of haemophilia A were reported in the second century AD, with the first modern description by John Conrad Otto in 1803. Historically, the natural history of haemophilia A was associated with very high rates morbidity and mortality, often following trivial accidents. Although treatment options for haemophilia A have been revolutionised in recent decades, haemophilia A remains a hereditary disease of concern and factor replacement products remain the mainstay of treatment.

As such, patients with haemophilia can carry huge burdens, particularly when a complication such as a FVIII inhibitor is present. A recently approved novel therapeutic, Emicizumab-kxwh, has …


Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell Jun 2022

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …


Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan May 2022

Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …


Flippase Inhibitors As Antimicrobial Agents, Robert Tancer May 2022

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …


Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria May 2022

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …


Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed May 2022

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …


A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang May 2022

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …


Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani May 2022

Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani

Mathematics, Physics, and Computer Science Faculty Articles and Research

At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection …


A Case Report On Causes Of Covid-19 Induced Psychosis And Treatments, Jennifer Pires, Steven Sarner May 2022

A Case Report On Causes Of Covid-19 Induced Psychosis And Treatments, Jennifer Pires, Steven Sarner

Rowan-Virtua Research Day

COVID-19 is a viral infection that is caused by an RNA virus in a subfamily of Coronaviridae named severe acute respiratory syndrome (SARS CoV 2). The family also includes severe acute respiratory syndrome coronavirus (SARS CoV) and middle east respiratory syndrome coronavirus (MERS CoV) which have previously been shown to cause respiratory symptoms and psychosis with immunoreactivity to IgG.