A5043443074- Kruppel-like factors research
- X-ray Diffraction in Crystallography
- Glaucoma and retinal disorders
- Mesenchymal stem cell research
- Crystallization and Solubility Studies
- RNA Interference and Gene Delivery
- Corneal surgery and disorders
- Corneal Surgery and Treatments
- Advanced biosensing and bioanalysis techniques
- Transplantation: Methods and Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cardiac Ischemia and Reperfusion
- Proteoglycans and glycosaminoglycans research
- Organ Transplantation Techniques and Outcomes
- Dendrimers and Hyperbranched Polymers
- Peroxisome Proliferator-Activated Receptors
- Chronic Myeloid Leukemia Treatments
- Autophagy in Disease and Therapy
- Natural Compounds in Disease Treatment
- Epigenetics and DNA Methylation
- Sirtuins and Resveratrol in Medicine
- Cancer-related gene regulation
- Retinal Development and Disorders
- Protein Hydrolysis and Bioactive Peptides
- Retinal Diseases and Treatments
University of Pittsburgh
2013-2024
Post Graduate Institute of Medical Education and Research
2012-2024
Amity University
2024
Jaypee Institute of Information Technology
2024
Rama University
2021
University of Pittsburgh Medical Center
2009-2019
Himachal Pradesh University
2011-2018
Indo Soviet Friendship College of Pharmacy
2018
Institute of Post Graduate Medical Education and Research
2016
Chandigarh University
2016
The vascular endothelium is a critical regulator of function. Diverse stimuli such as proinflammatory cytokines and hemodynamic forces modulate endothelial phenotype thereby impact on the development disease states. Therefore, identification regulatory factors that mediate effects these function considerable interest. Transcriptional profiling studies identified Kruppel-like factor (KLF)2 being inhibited by inflammatory cytokine interleukin-1β induced laminar shear stress in cultured human...
The vascular endothelium maintains blood fluidity by inhibiting coagulation, platelet aggregation, and promoting fibrinolysis. Endothelial cells lose these nonthrombogenic properties on exposure to proinflammatory stimuli. We recently identified the Kruppel-like factor KLF2 as a novel regulator of endothelial activation. Here it is found that differentially regulates key factors involved in maintaining an antithrombotic surface. Overexpression strongly induced thrombomodulin (TM) nitric...
The vascular endothelium plays a critical role in homeostasis. Inflammatory cytokines and non-laminar blood flow induce endothelial dysfunction confer pro-adhesive pro-thrombotic phenotype. Therefore, identification of factors that mediate the effects these stimuli on function is considerable interest. Kruppel-like factor 4 expression has been documented cells, but not described. In this communication we describe vitro vivo human mouse cells. Furthermore, demonstrate induced by...
Background— Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known to modulate endothelial function, the transcriptional mechanisms underlying these effects incompletely understood. We hypothesized that Lung-Kruppel–like factor (LKLF/KLF2), a novel and potent regulator of gene expression, may mediate downstream statins. Here we report statin-induced expression NO synthase (eNOS) thrombomodulin is KLF2 dependent. Methods Results— mRNA was induced by treatment...
The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory monocytes. In vitro, KLF2 expression in is reduced by cytokine or differentiation. Consistent with this observation, circulating patients chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression the LPS-mediated induction factors, cytokines, and chemokines reduces phagocytosis. Conversely,...
Cardiac hypertrophy is a common response to injury and hemodynamic stress an important harbinger of heart failure death. Herein, we identify the Kruppel-like factor 15 (KLF15) as inhibitor cardiac hypertrophy. Myocardial expression KLF15 reduced in rodent models biopsy samples from patients with pressure-overload induced by chronic valvular aortic stenosis. Overexpression neonatal rat ventricular cardiomyocytes inhibits cell size, protein synthesis hypertrophic gene expression. KLF15-null...
Low-density lipoprotein (LDL) cholesterol induces endothelial dysfunction and is a major modifiable risk factor for coronary heart disease. Endothelial Kruppel-like Factor 2 (KLF2) transcription that vital to endothelium-dependent vascular homeostasis. The purpose of this study determine whether how LDL affects KLF2 expression.LDL downregulates expression promoter activity in cells. LDL-induced decrease parallels changes target genes thrombomodulin, NO synthase, plasminogen activator...
Significance Many oxidative stimuli engage the 66-kDa Src homology 2 domain-containing protein (p66Shc) to induce reactive oxygen species (ROS). ROS regulated by p66Shc promotes aging and contributes cancer, diabetes, obesity, cardiomyopathy, atherosclerosis. Here we identify a fundamental mechanism that controls p66Shc-regulated ROS. We show is lysine acetylated when cells are faced with an stimulus (diabetes), acetylation of obligatory for p66Shc-induced In addition, lysine-acetylated...
Biological age, distinct from an individual's chronological has been studied extensively through predictive aging clocks. However, these clocks have limited accuracy in short time-scales. Here we trained deep learning models on fundus images the EyePACS dataset to predict individuals' age. Our retinal clocking, 'eyeAge', predicted age more accurately than other (mean absolute error of 2.86 and 3.30 years quality-filtered data UK Biobank, respectively). Additionally, eyeAge was independent...
Activation of the endothelium by inflammatory cytokines is a key event in pathogenesis vascular disease states. Proinflammatory repress expression KLF2, recently identified transcriptional inhibitor cytokine-mediated activation endothelial cells. In this study molecular basis for inhibition KLF2 elucidated. Tumor necrosis factor alpha (TNF-alpha) potently inhibited expression. This effect was completely abrogated constitutively active form IkappaBalpha, as well treatment with trichostatin A,...
Hyperhomocysteinaemia is an independent risk factor for atherosclerotic vascular disease and associated with endothelial dysfunction. Homocysteine modulates cellular methylation reactions. P66shc a protein that promotes oxidative stress whose expression governed by promoter methylation. We asked if homocysteine induces p66shc via hypomethylation of CpG dinucleotides in the promoter, whether mediates homocysteine-stimulated cell dysfunction.Homocysteine stimulates transcription human cells...
Low-dose acetylsalicylic acid (aspirin) is widely used in the treatment and prevention of vascular atherothrombosis. Cardiovascular doses aspirin also reduce systemic blood pressure improve endothelium-dependent vasorelaxation patients with atherosclerosis or risk factors for atherosclerosis. Aspirin can acetylate proteins, other than its pharmacological target cyclooxygenase, at lysine residues. The role acetylation mediating effects low-dose on endothelium not known.To determine...
To evaluate if p53 decreases Kruppel-Like Factor 2 (KLF2) expression and determine whether p53-mediated suppression of KLF2 plays a role in p53-induced endothelial dysfunction.Endothelial mediates endothelium-dependent vascular homeostasis by differentially regulating genes, leading to an anti-inflammatory antithrombotic surface with normal vasodilatory function. In contrast, the tumor suppressor leads inflammatory gene impairs vasodilatation, thus promoting dysfunction. The effect on was...
Objective— Reactive oxygen species regulate canonical Wnt signaling. However, the role of redox regulatory protein p66 Shc in pathway is not known. We investigated whether essential for signaling endothelium and determined induces vascular endothelial dysfunction via -mediated oxidative stress. Approach Results— The ligand Wnt3a induced phosphorylation (activation) cells. Wnt3a-stimulated dephosphorylation β-catenin, β-catenin–dependent transcription, was inhibited by knockdown . Exogenous H...
Liver regeneration is a spontaneous process that occurs after liver injury, but acute failure complex and fatal disease which difficult to treat. Cell-based therapies are promising alternative therapeutic approach for different cell sources have been tested in this regard. We investigated the comparative hepatogenic potential of human bone marrow stem cells (BMSC) with derived from dental pulp (DPSC), apical papilla (SCAP) follicle (DFSC) during study. Hepatogenic was assessed by functional...
Glaucoma is a leading cause of irreversible blindness. In this study, we investigated if transplanted stem cells are able to rescue glaucoma mouse model with transgenic myocilin Y437H mutation and explored the possible mechanisms. Human trabecular meshwork (TMSCs) were intracamerally which reduced intraocular pressure, increased outflow facility, protected retinal ganglion preserved their function. TMSC transplantation also significantly TM cellularity, promoted secretion from into aqueous...