A5089692286- Calcium signaling and nucleotide metabolism
- Nitric Oxide and Endothelin Effects
- Electron Spin Resonance Studies
- Adenosine and Purinergic Signaling
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Cardiovascular Function and Risk Factors
- SARS-CoV-2 and COVID-19 Research
- Ion channel regulation and function
- Ion Channels and Receptors
- Hemoglobin structure and function
- interferon and immune responses
- Cardiac Ischemia and Reperfusion
- Pharmacological Effects and Toxicity Studies
- Sirtuins and Resveratrol in Medicine
- Biocrusts and Microbial Ecology
- Animal Virus Infections Studies
- Eicosanoids and Hypertension Pharmacology
- Bioactive natural compounds
- COVID-19 Clinical Research Studies
- Redox biology and oxidative stress
- Cardiovascular and exercise physiology
Pfizer (United States)
2025
University of Pittsburgh
2020-2024
The Ohio State University
2014-2023
Pittsburg State University
2022
Lung Institute
2017
Peking University
2017
The Ohio State University Wexner Medical Center
2015
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), emerged at end and by mid-June 2020 virus had spread to least 215 countries, caused more than 8 000 confirmed infections over 450 deaths, overwhelmed healthcare systems worldwide. Like severe (SARS-CoV), which in 2002 a similar disease, SARS-CoV-2 is betacoronavirus. Both viruses use human angiotensin-converting enzyme (hACE2) as receptor enter cells. However, spike (S) glycoprotein...
Abstract The identity of the specific nitric oxide dioxygenase (NOD) that serves as main in vivo regulator O 2 -dependent NO degradation smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed fibroblasts and cells with unknown function. Cygb, coupled cellular reducing system, efficiently regulates rate consumption by metabolizing an manner decreased physiological hypoxia. Here we show Cygb major cardiovascular tone. Knockout greatly prolongs decay,...
In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although eNOS cofactor tetrahydrobiopterin (BH4) depleted, its repletion only partially restores eNOS-mediated vasodilation, indicating that other critical factors trigger dysfunction. Therefore, studies were performed characterize unidentified factor(s) dysfunction in heart. We observed depletion substrate NADPH occurs heart with near total from endothelium,...
We recently showed that ischemia/reperfusion (I/R) of the heart causes CD38 activation with resultant depletion cardiac NADP(H) pool, which is most marked in endothelium. This was shown to limit production nitric oxide by endothelial synthase (eNOS), requires NADPH for production, resulting greatly altered function. Therefore, intervention inhibitors could reverse postischemic eNOS-mediated dysfunction. Here, we evaluated potency inhibitor luteolinidin, an anthocyanidin, at blocking activity...
The NAD(P)+-hydrolyzing enzyme CD38 is activated in the heart during process of ischemia and reperfusion, triggering NAD(P)(H) depletion. However, presence role major cell types are unknown. Therefore, we characterize function cardiac myocytes, endothelial cells, fibroblasts. To comprehensively evaluate these measured gene transcription via mRNA, as well protein expression enzymatic activity. Endothelial cells strongly expressed CD38, while only low was present myocytes with intermediate...
The new era of messenger RNA (mRNA) vaccines has led to development a novel, state-of-the-art characterization method for this class molecules. Currently, flow cytometry-based assays with antigen-specific antibodies are utilized monitoring in-vitro expression (IVE) mRNA. Here we present development, optimization, and application an liquid chromatography tandem mass spectrometry (IVE-LC/MS/MS) assay as orthogonal IVE-flow cytometry that can be used in-depth the expressed protein antigens...
Inhibition of and genetic deletion the NAD(P)<sup>+</sup> hydrolase [NAD(P)ase] CD38 have been shown to protect against ischemia/reperfusion (I/R) injury in rat mouse hearts. has enhance salvage NADP(H), which turn prevents impairment endothelial nitric oxide synthase function, a hallmark dysfunction. Despite growing evidence for role postischemic injury, until recently there had lack potent inhibitors. Recently, new class thiazoloquin(az)olin(on)e compounds were identified as highly...
Abstract The reliability of plasma biomarkers Alzheimer's disease (AD) can be compromised by protease‐induced degradation. This limit the feasibility conducting biomarker studies in environments that lack capacity for immediate processing and appropriate storage blood samples. We hypothesized collection tube supplementation with protease inhibitors improve stability at room temperatures (RT). In this study, we conducted a comparative analysis traditional ethylenediaminetetraacetic acid...
Abstract SARS-CoV-2, the causative agent of COVID-19, emerged at end 2019 and by mid-June 2020, virus has spread to least 215 countries, caused more than 8,000,000 confirmed infections over 450,000 deaths, overwhelmed healthcare systems worldwide. Like SARS-CoV, which in 2002 a similar disease, SARS-CoV-2 is betacoronavirus. Both viruses use human angiotensin-converting enzyme 2 (hACE2) as receptor enter cells. However, spike (S) glycoprotein novel insertion that generates putative furin...
Insulin-like growth factor 1 (IGF-1)-dependent signalling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here, we test benefits on function using an model chronic catecholamine-induced cardiomyopathy.Rats were perfused with isoproterenol via osmotic pump (1 mg kg(-1) per day) and treated 2 (2 day, 6 days a week) or 4 weeks. Echocardiography, ECG, blood pressure assessed. In...
Cytoglobin (Cygb), like other members of the globin family, is a nitric oxide (NO) dioxygenase, metabolizing NO in an oxygen (O2)-dependent manner. We examined effect modification cysteine sulfhydryl groups Cygb on its O2 binding and dioxygenase activity. The two sulfhydryls were modified to form either intramolecular disulfide bond (Cygb_SS), thioether bonds N-ethylmaleimide (NEM; Cygb_SC), or maintained as free SH (Cygb_SH). It was observed that activity only slightly changed (~ 25%) while...
ABSTRACT INTRODUCTION The reliability of plasma Alzheimer’s disease (AD) biomarkers can be compromised by protease-induced degradation. This limits the feasibility conducting biomarker studies in environments that lack capacity for immediate processing and appropriate storage blood samples. We hypothesized collection tube supplementation with protease inhibitors improve stability at room temperatures (RT). study conducted a comparative analysis traditional ethylenediaminetetraacetic acid...
Purpose In continuous wave EPR imaging, the acquisition of high‐quality images was previously limited by requisite long times each image projection that typically greater than 1 second. To accelerate process facilitating numbers projections and higher resolution, instrumentation developed to greatly magnetic field scan is used obtain projection. Methods A low‐inductance solenoidal coil for scanning along with a spherical solenoid air core magnet, scans were driven triangular symmetric waves,...
Abstract Background The detection and monitoring of Alzheimer's disease (AD) biomarkers in plasma are crucial for early diagnosis prognosis. However, the stability AD can be compromised by degradation caused endogenous proteases present blood. efficacy protease inhibitors mitigating this is yet to established. This study evaluated five (GFAP, NFL, Aβ1‐40, Aβ1‐42, pTau181) over time under room temperature (RT) conditions. Samples were collected concurrently into either standard K2EDTA or...
Background: Vascular endothelial dysfunction (VED) is associated with increased oxidative stress due to eNOS uncoupling superoxide (•O2-) production and has important prognostic clinical implications for subsequent cardiovascular events. Our recent studies in hypertensive rats revealed a novel redox-regulated pathway through which uncoupled S-glutathionylation. However, its role human vascular disease remains unclear. Hence, we studied S-glutathionylation aortic tissue from patients...
Many studies have shown that cardiac overexpression of NOS enzymes can lead to myocardial protection against ischemia/reperfusion (I/R) injury. However, none these experiment with modulating BH 4 levels. Because adequate levels iNOS produce nitric oxide and inadequate damaging superoxide, we hypothesized depletion in a model constitutive expression would loss function diminished recovery post‐ischemic contractility. The study involved two groups TG mice: untreated mice treated mice. Treated...
CD38, a consumer of NAD+ and NADP+, is activated in I/R, leading to depletion myocardial NADP(H) consequently, lower eNOS function due low levels cofactor NADPH. Isolated hearts were subjected two treatments: pre‐ischemic luteolinidin (25μM) infusion or vehicle control (empty liposomes). In vehicle‐treated at 30’ ischemia reperfusion, NADPH BH 4 depleted by 67% 64% respectively. With 3’ (25μM), these numbers changed 23% 32% for , respectively, representing an impressive 44% salvage NADPH,...
Introduction: Cardiac ischemia/reperfusion (I/R) injury causes dysfunction in the coronary endothelium, resulting loss of vascular relaxation and decreased tissue perfusion. Prior data with pharmacological inhibitors suggests that CD38 plays a role I/R-induced endothelial (VED) through consumption NADPH precursor NADP, limiting supply for nitric oxide (NO) production from NO synthase (eNOS) decreasing NOS-dependent flow (NDCF). In order to definitively determine cardiac I/R dysfunction, we...
The “block and lock” strategy is one approach that might elicit a sterilizing cure for HIV-1 infection. “block” refers to compound’s ability inhibit latent proviral transcription, while the “lock” its capacity induce permanent silencing. We previously identified PF-3758309, pan-isoform inhibitor of p21-activated kinases (PAKs), as potent latency reversal. goal this study was define mechanism(s) involved. found both 24ST1NLESG cells (a cell line model latency) purified CD4+ naïve central...
Introduction Recently, we showed that CD38 activation in myocardial ischemia/reperfusion (I/R) injury causes depletion of the NADP(H) pool heart with near total from cardiac endothelium (1). This turn decreased NO production eNOS, limiting endothelial‐dependent vasodilation. Inhibiting protected higher recovery endothelial vasodilatory function, left ventricular contractile function and infarction. To test importance eNOS this protection, hearts WT eNOS‐deficient (eNOS −/− ) mice were...