Chemical Actions and Uses Commons^™

Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson

School of Medicine Faculty Publications

Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3–12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they …

Induction Of Antimicrobial Protein S100a15 Expression By Oral Microbial Pathogens Is Toll-Like Receptors-Dependent Activation Of C-Jun-N-Terminal Kinase (Jnk), P38, And Nf-Κb Pathways, Denis Selimovic, Naji Kharouf, Florence Carrouel, Sofie Yasmin Hassan, Thomas W. Flanagan, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli

Pharmacy Faculty Articles and Research

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system …

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B₃and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B₃are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD⁺decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD⁺levels. BHB is naturally produced by the body when individuals fast …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Chemical Composition And Behavioural Responses Of Male And Female Bactrocera Dorsalis To Their Volatile Emissions, Fikira Kimbokota

Journal of Humanities and Social Sciences

Bactrocera dorsalis, (Tephritidae) presented a grave threat to a broad range of fruit and vegetables in the tropics, including Tanzania. Bactrocera dorsalis is among the most destructive tephritid fruit fly, causing devastating loss of fruits especially mango. Insects use olfactory cues to locate hosts, oviposition sites and mating, in which pheromones are believed to be a strong cue used by insect to locate their mates. However, due to their high ability to adapt and occupy different ecological niches into various agroecological zones, there is a need to evaluate pheromonal composition from time to time to improve their control strategies. Therefore, …

The Evaluation Of Mefloquine Drug Repurposing On Acute Myeloid Leukemia, Jessica L. Phan, Bhavuk Garg, Hrishikesh Mehta, Seth Corey

Undergraduate Research Posters

The aim of this study is to observe cell proliferation, cell viability, apoptosis, and autophagy on acute myeloid leukemia (AML) cell lines, NB4 and U937, with the drug repurposing of mefloquine (MQ). Methods such as the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and trypan blue staining have shown a decrease in live cells with high concentrations of mefloquine. Using their average perspective IC50 values of MQ concentration, Western blotting was applied by means of apoptosis and autophagy markers to determine if the induction of apoptosis and inhibition of autophagy was present in MQ-treated AML cells. The experiment will be continued with more …

Chemical Modulation Of Cancer Cells To Enhance Tumor Immunity, Florisela Herrejon Chavez

PSU McNair Scholars Online Journal

Breakthroughs in immunotherapy have led to cancer therapeutics that activate the immune system by blocking inhibitory mechanisms. This class of therapeutics has resulted in longer survival rates for cancer patients, some living over 10 years after being diagnosed as terminally ill. However, only a small fraction of patients who receive immunotherapy drugs respond favorably.Recent studies suggest that certain anticancer agents (both cytotoxic chemotherapeutics and targeted drugs) stimulate immune recognition of cancers. Identification of such immunomodulatory anticancer agents would make ideal partners for current immunotherapy treatments, thus increasing the proportion of the treated patients who benefit from immunotherapy. This study aimed …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

Effects Of (R)-(-)-5-Methyl-1-Nicotinoyl-2-Pyrazoline On Glutamate Transporter 1 And Cysteine/Glutamate Exchanger As Well As Ethanol Drinking Behavior In Male, Alcohol-Preferring Rats, Munaf Aal-Aaboda, Hasan Alhaddad, Francis Osowik, Surya M. Nauli, Youssef Sari

Pharmacy Faculty Articles and Research

Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We recently showed that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. This study examines the effect of a synthetic compound, (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expressions of …

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Development Of Affinity Microcolumns For Drug–Protein Binding Studies In Personalized Medicine: Interactions Of Sulfonylurea Drugs With In Vivo Glycated Human Serum Albumin, Jeanethe Anguizola, K. S. Joseph, Omar S. Barnaby, Ryan Matsuda, Guadalupe Alvarado, William Clarke, Ronald Cerny, David S. Hage

David Hage Publications

This report used high-performance affinity microcolumns to examine the changes in binding by sulfonylurea drugs to in vivo glycated HSA that had been isolated from individual patients with diabetes. An immunoextraction approach was developed to isolate HSA and glycated HSA from clinical samples, using only 20 μL of plasma or serum and 6–12 nmol of protein to prepare each affinity microcolumn. It was found that the affinity microcolumns could be used in either frontal analysis or zonal elution studies, which typically required only 4–8 min per run. The microcolumns had good stability and allowed data to be obtained for multiple …

Regulation Of Alpha Synuclein Following Chronic Methamphetamine Administration In Guinea Pigs: Correlation With Memory And Synaptic Plasticity, Adnouse Blanc

PCOM Biomedical Studies Student Scholarship

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were …

Environmental Friendly Synthesis, Characterization Of Surface Modifiable Starch Encapsulated Gold Nanoparticles With Bactericidal And Catalytic Activity, Dillon Pender

Mahurin Honors College Capstone Experience/Thesis Projects

In the present study, we report the green synthesis of gold nanoparticles (GNPs), using potato starch as a reducing as well as a stabilizing agent in an aqueous buffer medium. The resulting starch-GNPs (St-GNPs) were near spherical in shape with an average diameter of 15 ± 5 nm. In this approach, St-GNPs were characterized and investigated for their antibacterial properties against both gram negative (Escherichia coli) and gram positive (Staphylococcus epidermidis) bacteria. These St-GNPs were found to possess significant dose dependent antibacterial activity against bacteria. Also, St-GNPs showed a significant catalytic activity and can easily be …