Chemicals and Drugs Commons^™

Impact Of Fads Genotype On Polyunsaturated Fatty Acid Content In Human Milk Extracellular Vesicles: A Genetic Association Study, John J. Miklavcic, Natalie Paterson, Jennifer Hahn-Holbrook, Laura M. Glynn

Food Science Faculty Articles and Research

Background

Extracellular vesicles in human milk are critical in supporting newborn growth and development. Bioavailability of dietary extracellular vesicles may depend on the composition of membrane lipids. Single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase gene cluster impact the content of long-chain polyunsaturated fatty acids in human milk phospholipids. This study investigated the relation between variation in FADS1 and FADS2 with the content of polyunsaturated fatty acids in extracellular vesicles from human milk.

Methods

Milk was obtained from a cohort of mothers (N = 70) at 2–4 weeks of lactation. SNPs in the FADS gene locus were determined using …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

The Effect Of Ethanol Treatment On The Protein Content Of Difi Exosomes, Kenzie Rushing

Belmont University Research Symposium (BURS)

Colorectal cancer (CRC) is the second most common cause of cancer death in the United States in both men and women combined, second only to lung cancer.1 CRC metastasis is the primary cause of mortality largely due to therapy resistant cancer cells.2 Therefore, detection before metastasis is of great importance and could potentially lead to earlier detection and decreased mortality. Extracellular vesicles (EVs), including exosomes, are lipid bound vesicles secreted by cells3 that are involved in cell-cell communication and have been found to promote CRC progression and metastasis.4 The proteome of exosomes is thought to reflect that of the originating …

Β-Sheets Mediate The Conformational Change And Allosteric Signal Transmission Between The Aslov2 Termini, Sian Xiao, Mayar Terek Ibrahim, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ …

Measurement And Imaging Of Intra Matrix Igg Diffusion, Riya Debbarma, Antonio C. F. Dos Santos, Diana Milena Ramiez Gutierrez, Fernanda M. Da Cunha, Michael Ladisch

Graduate Industrial Research Symposium

Bovine IgG diffusion measurement by tracking the movement of the protein over time in an in-vitro matrix is motivated by the large number of protein/peptide therapeutics currently under various stages of development in the pharmaceutical industry. Many of these therapeutics are monoclonal antibodies (IgG type proteins) that are candidates for subcutaneous, intra-vitreous and intra-articular administration depending on the target of the therapeutic. Hyaluronic acid (HA) is a major constituent and determines the key attributes of the subcutaneous environment, vitreous humor of the eye and synovial fluid of the knee joint. HA exhibits varying molecular weight at these anatomic locations thereby …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Evaluation Of Novel Therapeutic Agents For The Treatment Of Chronic Dry Eyes, Lilian Huynh, Evonie Villarete, Surajit Dey

Annual Research Symposium

Dry eye disease (DED) is a multifactorial ocular condition, where disrupted tear film stability and ocular surface inflammation affected between 5% to 34% of the worldwide population in 2015 and posed a challenge to conventional ophthalmic treatments. Recent advances have led to potential novel therapeutics aiming to alleviate symptoms and improve patient outcomes.

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Variables Affecting The Extraction Of Antioxidants In Cold And Hot Brew Coffee: A Review, Brian Yust, Frank Wilkinson, Niny Rao

College of Life Sciences Faculty Papers

Coffee beans are a readily available, abundant source of antioxidants used worldwide. With the increasing interest in and consumption of coffee beverages globally, research into the production, preparation, and chemical profile of coffee has also increased in recent years. A wide range of variables such as roasting temperature, coffee grind size, brewing temperature, and brewing duration can have a significant impact on the extractable antioxidant content of coffee products. While there is no single standard method for measuring all of the antioxidants found in coffee, multiple methods which introduce the coffee product to a target molecule or reagent can be …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Tiny But Mighty, An Exploration Of Microbes And Plants As Sources Of Small Novel Bioactive Compounds Against Invasive Mycoses., Hannah Mai Peacock, James Anthony O'Connor

SURE Journal: Science Undergraduate Research Experience Journal

Despite the high mortality rate involved with invasive cerebral mycoses, there is a relative lack of research available around antifungals capable of crossing the blood brain barrier.

In this study the metabolites of four plants (Crocus vernus, Miniature Narcissus (daffodil), Osmanthus delavayi and Taraxacum officinale (common dandelion)) and two bacteria (Lacticaseibacillus paracasei and Staphylococcus epidermidis) were extracted and assayed for antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thin layer chromatography and bioautography were then employed to assess the activity of the constituent components of sources showing antifungal activity.

Metabolites of S.epidermidis, and extracts …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle

School of Graduate Studies Faculty Publications

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Chemical Modification And Evaluation Of Cells Towards Use As Delivery Tools, Bishnu Prasad Joshi

Doctoral Dissertations

CHEMICAL MODIFICATION AND EVALUATION OF CELLS TOWARDS USE AS DELIVERY TOOLS SEPTEMBER 2023 BISHNU PRASAD JOSHI M.S., SRI SATHYA SAI INSTITUTE OF HIGHER LEARNING Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Michelle E. Farkas Endogenous cells are being studied for use in various applications, such as next generation therapeutics and drug delivery vehicles. This is on account of their biocompatibility, amenable distribution profiles, and in many instances, recruitment to and localization of diseased tissues. Multiple cell types have been employed, including macrophages, stem cells, red blood cells, and T cells. Most examples of cell-based delivery utilize phagocytosed entities as …

Monitoring The Leaching Of Bisphenol-A From Feminine Hygiene Products Using Fluorescence Spectroscopy, Madison Easley

Honors Theses

Bisphenol-A (BPA) is a compound commonly used as a stabilizer in plastic products, including food storage containers and thermal paper receipts. Because BPA can bind to and activate estrogen receptors, it is linked to reduced fertility, altered development, and hormone-related cancers. A recent study at NYU Medical School confirmed the presence of BPA in pantyliners, pads, tampons, feminine washes and deodorants. This is concerning due to the high absorption capacity of the vulvar skin.

For the research performed in our lab this summer, the goal was to determine if fluorescence spectrophotometry could be used to determine the presence of BPA …

Determining The Ideal Concentrations Of Ethanol And Propylene Glycol In Ethosomes For Transdermal Delivery Of Vitamin D3, Rebecca Conner

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Vitamin D₃ is an important chemical in the human body, however, many Americans have low levels of this vitamin. There are plenty of oral supplementations for Vitamin D₃ deficiency, but those of older age and busy schedules may struggle to meet the minimum requirement. A recently developed ethosomal transmembrane delivery system (Touitou, 2000), similar to liposomes but also containing ethanol, allows users to apply a gel dermally and have the desired drug or active ingredient reach the bloodstream faster. However, there is considerable variation in the concentration of ethanol and permeation enhancers used. Using an affordable method to …

Understanding An Inflammatory Pathway In Diabetic Retinopathy, Reanna R. Rodriguez

Research Symposium

Diabetic Retinopathy (DR) is the leading cause of blindness in the U.S. However, not much is known of its molecular pathway and how it attributes to increases in inflammatory response in the eye. One avenue we will investigate is the transforming growth factor beta (TGFB) signaling pathway and its effect of vascular endothelial growth factor (VEGF) secretion and cell viability. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concern that have arisen are the underlying effects of oxidants and antioxidants in elevating VEGF secretion in diabetes. In attempt to learn more, we evaluated how an …

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …

Identification Of Tectorigenin As A Natural Pro-Hypoxia Compound: Implications In Modulation Of Cellular Differentiation And Senescence, Mallika Khurana, Renu Wadhwa, Sunil Kaul

Research Symposium

Background: Hypoxia, a suboptimal level of oxygen, evokes stress response in cells and activated hypoxia signaling has been largely established as a pro-metastasis and pro-angiogenic factor for tumor cells. On the other hand, age-related neurodegenerative disorders are characterized by hypoxic environment, accumulation of molecular garbage and induction of premature senescence. Several recent studies have reported anti-stress impact of the intermittent induction of hypoxia signaling in these cells.

Methods: Screening of a phytochemical library using Hypoxia Responsive Element (HRE) driven luciferase as a reporter was carried out to identify hypoxia-modulating phytochemicals. Activation of HIF-1a (master regulator of hypoxia signaling) was validated …

Differential Cortical Monoamines Release During Exercise In Rats Chronically Implanted With Microdialysis Probes, Christine G. Gerin

Research Symposium

Physical exercise is known to positively influence mood, to reduce anxiety and to improve reaction to stress. Cerebral monoaminergic systems are thought to underly the neurochemical influence of exercise on mood and behavior. We hypothesized that beneficial effects of exercise can be shown by variations of neurotransmitters release in the cerebral cortex. We aimed at demonstrating that there is a temporal relationship between release of plasma and cerebral monoamines (A, NA, 5-HT, DA) and spontaneous running exercise in rats. Ten Spague Dawley rats (250 g) were chronically implanted (for up to 39 days) with a left common carotid cannula and …

Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

No abstract provided.

All-Cause And Opioid-Related Mortality Compared Between Traumatic Spinal Cord Injury And The Us General Population, Jaden Whitehead, Beatrice Ugiliweneza

The Cardinal Edge

Individuals with spinal cord injury (SCI) are susceptible to the misuse of opioids due to the introduction of these substances for pain management. There are very few studies examining the relationship between unintentional deaths caused by opioid usage following spinal cord injury. The objective of this study was to evaluate the trend of opioid-related mortality of individuals with spinal cord injury (SCI) over the years and compare these findings to the mortality rates due to opioid misuse in the general population. In this study, we used data provided by the National Spinal Cord Injury Model Systems (NSCIMS) for SCI 1999-2016 …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …