A5024661668- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Metabolomics and Mass Spectrometry Studies
- Gut microbiota and health
- Diet and metabolism studies
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Amyotrophic Lateral Sclerosis Research
- Electron Spin Resonance Studies
- Forensic Toxicology and Drug Analysis
- Analytical Chemistry and Chromatography
- Epigenetics and DNA Methylation
- Calpain Protease Function and Regulation
- Computational Drug Discovery Methods
- Birth, Development, and Health
- Cholinesterase and Neurodegenerative Diseases
- Redox biology and oxidative stress
- Phosphodiesterase function and regulation
- Eicosanoids and Hypertension Pharmacology
- Advancements in Transdermal Drug Delivery
- Respiratory and Cough-Related Research
- Williams Syndrome Research
University of Toledo
2016-2025
Northwestern University
2023
Texas Tech University
2014
Texas Tech University Health Sciences Center
2014
University of Illinois Chicago
2010-2013
Illinois College
2013
Furoxans (1,2,5-oxadiazole-N-oxides) are thiol-bioactivated NO-mimetics that have not hitherto been studied in the CNS. Incorporation of varied substituents adjacent to furoxan ring system led modulation reactivity toward bioactivation, by HPLC-MS/MS analysis reaction products. Attenuated unmasked cytoprotective actions NO contrast cytotoxic higher fluxes reported previously for furoxans. Neuroprotection was observed primary neuronal cell cultures following oxygen glucose deprivation (OGD)....
Abstract The rapid increase in use of electronic-cigarettes (e-cigarettes), especially among youth, raises the urgency for regulating bodies to make informed decisions, guidance, and policy on these products. This study evaluated cardiac function an experimental model following exposure e-cigarettes. We subjected C57BL/6 mice e-cigarette vaping 2-weeks, was assessed using echocardiography. Cardiac tissues were collected at end pathological analysis. data showed that (3 h/day 14 days) had no...
Despite the availability of various classes antihypertensive medications, a large proportion hypertensive individuals remain resistant to treatments. The reason for what contributes low efficacy medications in these is elusive. knowledge that gut microbiota involved pathophysiology hypertension and drug metabolism led us hypothesize catabolize compromised their blood pressure (BP)-lowering effects.To test this hypothesis, we examined BP responses representative ACE (angiotensin-converting...
The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with estrogens in protection of primary rat neurons against oxygen-glucose deprivation (OGD). Structure-activity relationships for neuroprotection were determined a family BT-SERMs displaying spectrum ERα and ERβ binding affinity agonist/antagonist activity, leading to discovery neuroprotective pharmacophore, present the clinically relevant SERMS, raloxifene desmethylarzoxifene (DMA), which submicromolar potency observed...
Amyotrophic lateral sclerosis (ALS) is a progressive and ultimately fatal neurodegenerative disease. Pyrazolone containing small molecules have shown significant disease attenuating efficacy in cellular murine models of ALS. based affinity probes were synthesized to identify high binding partners ascertain potential biological mode action. Probes confirmed be neuroprotective PC12-SOD1G93A cells. cell lysates used for protein pull-down, purification, subsequent proteomic analysis using...
Protein S-nitrosation has been argued to be the most important signaling pathway mediating bioactivity of NO. This post-translational modification protein thiols is result chemical nitrosation cysteine residues. The term NO-donors covers very different classes, from clinical therapeutics probes routine use in biology; their chemistry predicted distinctive biology regulated by S-nitrosation. To measure extent NO-donors, a proteomic mass spectrometry method was developed, which quantitates...
Abstract Use of synthetic psychoactive cathinones (SPCs) has been increasing worldwide over the past two decades, although true extent SPC use and abuse is probably underestimated. SPCs have similar structures to amphetamines mimic stimulant other effects depending on structural motifs that give them properties are methamphetamine (METH), methylenedioxymethamphetamine (MDMA), or cocaine. As 400 illicitly used, high throughput behavioral toxicological approaches being developed this diverse...
Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Cal1) is implicated as a primary or secondary pathological event in wide range illnesses and neurodegenerative states, including Alzheimer's disease (AD). E-64 an epoxide-containing natural product identified potent nonselective, inhibitor, with demonstrated efficacy animal models AD. By use lead, three successive generations inhibitors were developed using computationally assisted design to increase selectivity for Cal1....
Co-metabolism between a human host and the gastrointestinal microbiota generates many small phenolic molecules such as 3-hydroxy-3-(3-hydroxyphenyl)propanoic acid (3,3-HPHPA), which are reported to be elevated in schizophrenia autism. Characterization of these chemicals, however, has been limited by analytic challenges.We applied HPLC separate quantify over 50 analytes, including multiple structural isomers 3,3-HPHPA cerebrospinal fluid, serum urine. Confirmation identity was provided NMR,...
Alzheimer's disease, one of the most important brain pathologies associated with neurodegenerative processes, is related to overactivation calpain-mediated proteolysis. Previous data showed a compelling efficacy calpain inhibition against abnormal synaptic plasticity and memory produced by excess amyloid-β, distinctive marker disease. Moreover, beneficial effect inhibitors in disease predictable occurrence hyperactivation leading impairment memory-related pathways following calcium influxes...
Poor blood-brain barrier penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been blamed for the failure selective amyloid lowering agent (SALA) R-flurbiprofen in phase 3 clinical trials Alzheimer's disease (AD). NO-donor NSAIDs (NO-NSAIDs) provide an alternative, gastric-sparing approach to NSAID SALAs, which may improve bioavailability. analogues were studied activity and SALA N2a neuronal cells transfected with human precursor protein (APP). Flurbiprofen (1) obtained enhanced...
Abstract Allosteric modulation of muscarinic acetylcholine receptors (mAChR) has been identified as a potential strategy for regulating cholinergic signaling in the treatment various neurological disorders. Most positive allosteric modulators (PAMs) mAChR enhance agonist affinity and potency, while very few PAMs selectively G-protein coupling efficacy (e.g., amiodarone). The key structural features amiodarone responsible enhancement were examined CHO cells expressing M 1 receptors....
Nitric oxide (NO) mimetics and other agents capable of enhancing NO/cGMP signaling have demonstrated efficacy as potential therapies for Alzheimer's disease. A group thiol-dependent NO known furoxans may be designed to exhibit attenuated reactivity provide slow onset effects. The present study describes the design, synthesis, evaluation a furoxan library resulting in identification prototype furoxan, 5a, which was profiled use central nervous system. Furoxan 5a negligible toward generic...
Hybrid nitrate drugs have been reported to provide NO bioactivity ameliorate side effects or ancillary therapeutic activity. selective serotonin reuptake inhibitors (NO-SSRIs) were prepared improve the profile of this drug class. A synthetic strategy for use a thiocarbamate linker was developed, which in case NO-fluoxetine facilitated hydrolysis fluoxetine at pH 7.4 within 7 h. In cell culture, NO-SSRIs weak transporter; however, forced swimming task (FST) rats, demonstrated classical...
Short-chain fatty acids (SCFAs) produced by the gut bacteria have been associated with cardiovascular dysfunction in humans and rodents. However, studies exploring effects of SCFAs on parameters zebrafish, an increasingly popular model research, remain limited. Here, we performed fecal bacterial 16S sequencing gas chromatography/mass spectrometry (GC-MS) to determine composition abundance microbiota adult zebrafish. Following this, acute major heart rate vascular tone were measured...
Photoaffinity labeling (PAL) remains one of the most widely utilized methods determining protein targets drugs. Although useful, scope this technique has been limited to in vitro applications because inability UV light penetrate whole organisms. Herein, pigment-free Casper zebrafish were employed allow vivo PAL. A methamphetamine-related phenethylamine PAL probe, designated here as 2, demonstrated dose-dependent effects on behavior similar methamphetamine and permitted...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure, and current treatment options are very limited. Previously, we performed high-throughput screen to identify small molecules that inhibit protein aggregation caused by mutation in the gene encodes superoxide dismutase 1 (SOD1), which responsible for about 25% of familial ALS. This resulted three hit series compounds were optimized over several years give highly active mutant SOD1 ALS model. Here target two...
Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected sulfation by several zebrafish cytosolic sulfotransferases (SULTs).We were interested in finding out which human SULT(s) is(are) capable catalyzing dextrorphan, and verify whether dextrorphan may occur cultured cells organ cytosols.Data from enzymatic assays showed that, all thirteen known SULTs, SULT1A3 displayed strongest dextrorphansulfating activity.Cell culture experiments using HepG2...