A5087916145- Telomeres, Telomerase, and Senescence
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nitric Oxide and Endothelin Effects
- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Adipose Tissue and Metabolism
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Cardiovascular Health and Disease Prevention
- Calcium signaling and nucleotide metabolism
- Exercise and Physiological Responses
- Occupational Health and Performance
- Advanced biosensing and bioanalysis techniques
- Sports injuries and prevention
- Antioxidant Activity and Oxidative Stress
- Metal-Catalyzed Oxygenation Mechanisms
- Injury Epidemiology and Prevention
- Click Chemistry and Applications
- PARP inhibition in cancer therapy
- Advanced Fluorescence Microscopy Techniques
- Single-cell and spatial transcriptomics
- Atherosclerosis and Cardiovascular Diseases
- Hormonal Regulation and Hypertension
- Sodium Intake and Health
- Blood transfusion and management
- Ergonomics and Musculoskeletal Disorders
University of Utah
2018-2024
Skidmore College
2017-2022
University of Illinois Chicago
2019
North Carolina Agricultural and Technical State University
2019
University of Memphis
2019
United States Department of Homeland Security
2019
Jefferson Hospital
1953
DNA-encoded chemical libraries are increasingly used in pharmaceutical research because they enable the rapid discovery of synthetic protein ligands. Here we explored whether target-class focused can be cost-effective tools to achieve robust screening productivity for a series proteins. The study revealed that library designed NAD+-binding pockets (NADEL) effectively sampled binder space enzymes with ADP-ribosyltransferase activity. extracted information directed synthesis inhibitors several...
Age-related microvascular dysfunction is well characterized in rodents and humans, but little known about the properties of endothelial glycocalyx advanced age. We examined microvessels young old male C57BL6 mice (young: 6.1 ± 0.1 mo vs. old: 24.6 0.2 mo) using intravital microscopy transmission electron human participants 29 1 yr 60 2 yr) microscopy. Glycocalyx thickness mesenteric skeletal muscle was 51-54% lower compared with mice. also observed 33% sublingual microcirculation humans The...
Abstract In advanced age, increases in oxidative stress and inflammation impair endothelial function, which contributes to the development of cardiovascular disease (CVD). One plausible source this is an increase abundance senescent cells. Cellular senescence a cell cycle arrest that occurs response various damaging stimuli. present study, we tested hypothesis age results telomere dysfunction induces senescence. both human mouse cells, resulted increased dysfunctional telomeres,...
Abstract Systemic inhibition of the mammalian target rapamycin (mTOR) delays aging and many age‐related conditions including arterial metabolic dysfunction. However, mechanisms tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation S6K, a downstream mTOR, is increased arteries with advancing age, this occurs preferentially endothelium compared vascular smooth muscle. Induced endothelial cell‐specific deletion mTOR reduced protein expression...
Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with advancing age being primary, nonmodifiable risk factor. Vascular dysfunction, namely arterial stiffening and endothelial is key antecedent to development clinical CVD aging. Fundamental aging macro-mechanistic processes that drive vascular include excess oxidative stress, chronic inflammation, declines in vasodilatory molecule nitric oxide. An important hallmark contributes cellular senescence - a stress response...
Background An acute bout of eccentric contractions (ECC) cause muscle fiber damage, inflammation, impaired function (MF) and soreness (MS). Individually, protein (PRO) antioxidant (AO) supplementation may improve some aspects recovery from ECC, though have yet to be combined. We sought determine if combined PRO AO (PRO + AO) improves MS MF following damaging ECC over alone.Methods Sixty sedentary college-aged males participated in a randomized, single–blind, parallel design study peak...
Increased large artery stiffness and impaired endothelium-dependent dilatation occur with advanced age. We sought to determine whether T cells mechanistically contribute age-related arterial dysfunction. found that old mice exhibited greater proinflammatory cell accumulation around both the aorta mesenteric arteries. Pharmacologic depletion or genetic deletion of in resulted ameliorated compared intact.
Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that vascular endothelium plays a crucial role in systemic resistance; however, underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) small GTPase critical endothelial cell function. Here, tested hypothesis deletion will result resistance.
Obesity and aging are linked to inflammation increased risk of chronic disease. Telomeres the endcaps chromosomes that regulated by telomerase, enzyme elongates telomeres, as well a protein complex known shelterin. Telomere dysfunction is associated with inflammation, aging, However, effect high-fat diet (HFD) induced obesity advancing age on shelterin telomerase in adipose tissue unknown. The present study investigated effects C57BL/6J mice mRNA expression genes. Young (YG) (3 mo) were...
Objective: Sudden cardiac events account for 40% to 50% of firefighter line-of-duty deaths. Inflammatory proteins are strong biomarkers cardiovascular inflammation. The present study investigated the effects aspirin supplementation on inflammatory following firefighting. Methods: Using a randomized, placebo-controlled, double-blind crossover design, 24 male firefighters (48.2 ± 5.9 years) were allocated into four conditions: acute (81 mg; single-dose) and placebo supplementation, chronic 14...
Advanced age is the greatest risk factor for cardiovascular disease (CVD), leading cause of death. Arterial function impaired in advanced which contributes to development CVD. One underexplored hypothesis that DNA damage within arteries leads this dysfunction, yet evidence demonstrating incidence and physiological consequences arteries, particular, microvasculature, limited. In present study, we began by assessing abundance human mouse lung microvascular endothelial cells found aging...
While the fire service has long been a male-dominated occupation, women's participation in this strenuous, high risk, performance activity increased recent years. Firefighting induces significant cardiovascular strain, including hemostatic disruption; however, effect of sex on responses not investigated despite evidence that there are sex-related differences variables at rest and following exercise. Thus, we age- BMI-matched male female firefighters who performed 3-4 evolutions firefighting...
Abstract Background Much of what we know about insulin resistance is based on studies from metabolically active tissues such as liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic resistance, however, underlying mechanisms remain incompletely understood. ADP ribosylation factor 6 (Arf6) small GTPase critical endothelial cell (EC) function. Here, tested hypothesis deletion Arf6 will result resistance. Methods We...
Aging results in an accumulation of cellular damage that activates tumor suppressor pathways leading to permanent cell cycle arrest known as senescence. Damage DNA is a robust inducer Furthermore, repeat sequences at the ends chromosomes telomeres are particularly susceptible leads Senescent cells adopt pro-oxidative, pro-inflammatory phenotype often adversely impacts local tissue milieu. Senolytics drugs specifically induce death senescent cells. Senolytic have been shown delay or reduce...
Cardiovascular toxicity is one of the adverse consequences chemotherapy that limits treatment. Specifically, chemotherapeutics such as doxorubicin (DOXO) can lead to endothelial dysfunction through induction reactive oxygen species (ROS) and mitochondrial ROS (mtROS) production. MtROS are chemically molecules generated byproducts oxidative phosphorylation during respiration. DOXO exacerbates its cardiotoxic effects by amplifying mtROS production, leading an increase in DNA damage cell...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to "A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors NAD+-Dependent Enzymes"Lik Hang YuenLik YuenMore by Lik Yuen, Srikanta DanaSrikanta DanaMore Danahttps://orcid.org/0000-0003-0503-3082, Yu LiuYu LiuMore Liu, Samuel I. BloomSamuel BloomMore Bloom, Ann-Gerd ThorsellAnn-Gerd ThorsellMore Thorsell, Dario NeriDario NeriMore Neri, Anthony J. DonatoAnthony...
Advancing age leads to an accumulation of senescent endothelial cells (ECs) within arteries. Senescent have undergone permanent cell cycle arrest, are pro-oxidative and pro-inflammatory, therefore represent a likely cause age-related EC dysfunction. Yet, the molecular mechanisms physiological consequences senescence remain incompletely understood. Telomeres repeat DNA sequences that cap chromosomes. shorten with each division highly susceptible oxidative damage. When telomeres become...
Aging results in cellular damage that can induce cell cycle arrest known as senescence. Endothelial cells are one of the first types to become senescent advancing age and contribute age-related cardiovascular diseases. Drugs senolytics reduce endothelial senescence culture. From a translational perspective, key question is whether this occurs vivo if remaining appear healthier display fewer hallmarks aging. In study, we treated old mice with senolytic cocktail dasatinib quercetin (D+Q) or...