- Protease and Inhibitor Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Angiogenesis and VEGF in Cancer
- Tissue Engineering and Regenerative Medicine
- Pulmonary Hypertension Research and Treatments
- Connective tissue disorders research
- Cerebrovascular and Carotid Artery Diseases
- Muscle Physiology and Disorders
- Bone and Dental Protein Studies
- Adipose Tissue and Metabolism
- Tuberous Sclerosis Complex Research
- Venous Thromboembolism Diagnosis and Management
- Cardiovascular Function and Risk Factors
- Heparin-Induced Thrombocytopenia and Thrombosis
- Blood properties and coagulation
- Cancer Cells and Metastasis
- Electrospun Nanofibers in Biomedical Applications
- Muscle and Compartmental Disorders
- Herpesvirus Infections and Treatments
- Ion channel regulation and function
- Cytomegalovirus and herpesvirus research
University of Pennsylvania
2012-2024
City Hospital No. 40
2021-2023
St. Petersburg State Medical Academy "City Hospital No. 26"
2021
National Medical Research Center of Cardiology
2019
Philadelphia University
2017
Faculty (United Kingdom)
2016
Lomonosov Moscow State University
2016
United States National Library of Medicine
2015
University of Rochester
2015
National Institutes of Health
2015
Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder initiated by antibodies to complexes between platelet factor 4 (PF4) and heparin. The risk of recurrent thromboembolism persists after heparin cleared activation leading release PF4 has dissipated. We asked whether antigenic polyphosphates released from activated platelets might intensify or sustain the prothrombotic phenotype HIT. forms stable, ultralarge with various sizes, including those platelets, which are recognized...
Urokinase plasminogen activator (uPA) is thought to exert its effects on cell growth, adhesion, and migration by mechanisms involving proteolysis interaction with surface receptor (uPAR). The functional properties of uPA the significance various domains for chemotactic activity were analyzed using human airway smooth muscle cells (hAWSMC). wild-type (r-uPAwt), inactive urokinase single mutation (His204 Gln) (r-uPAH/Q), His204to Gln together a deletion growth factor-like domain...
Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality believed to be presence cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but mechanisms responsible are unclear. Recently poor prognosis PDAC has been correlated with increased expression urokinase plasminogen activator (uPA). In present study we examine role uPA in generation CSC. We observe a subset identifiable as side population (SP) when sorted...
This article is dedicated to analyzing the approaches evaluating impact of digitalization on quality life population. The relevance topic due fact that digital transformation has a complex im-pact various spheres society, including standard and people. study examines theoretical foundations this concept its primary components. It analyzes existing methodologies for as-sessing life, such as Digital Development Index, Com-petitiveness Networked Readiness Index. strengths limitations these are...
Chemical coupling to carrier red blood cells (RBCs) converts tissue type plasminogen activator (tPA) from a problematic therapeutic into safe agent for thromboprophylaxis. The goal of this study was develop more clinically relevant recombinant biotherapeutic by fusing mutant tPA with single-chain antibody fragment (scFv) specificity glycophorin A (GPA) on mouse RBCs. fusion construct (anti-GPA scFv/PA) bound specifically but not human RBCs and activated plasminogen; led rapid stable...
Urokinase plasminogen activator (uPA) is required for both endogenous and vascular endothelial growth factor (VEGF)–augmented angiogenesis in normal tissues, leading us to hypothesize that uPA augmentation by gene transfer might promote ischemic tissues. Overexpression of was studied rat myocardial infarction (MI) mouse hind limb ischemia models compared with VEGF overexpression effects. Animals were divided into control three experimental groups (n = 6), receiving intramuscular injections...
We have explored intracellular pathways involved in the urokinase type plasminogen activator (urokinase or uPA)stimulated migration of human airway smooth muscle cells (hAWSMC). Using a set uPA mutants we found that protease activity, growth factorlike and kringle domains differentially contribute to activation p42/p44erk1,2 p38 MAPkinases. Consistent with our earlier data [Mukhina et al., J. Biol. Chem. 275 (2000), 16450 16458], domain was sufficient required stimulate cell motility. Here...
The article discusses the life of Danish Dr. Halfdan Mahler who also served as Secretary-General World Health Organization (WHO), and it mentions Mahler's work involving Declaration Alma-Ata in September 1978 which WHO, United Nations Children's Fund, 134 signatory nations declared for All by 2000 goal. Social justice global public health history are examined, along with care accessibility attitudes activists.
The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk bleeding due lysis hemostatic clots that hemorrhage in damaged blood vessels. We sought develop agent provides thromboprophylaxis without carrying a significant causing systemic fibrinolysis or disrupting clots. previously showed platelet (PLT) α granule-delivered urokinase plasminogen activator (uPA) highly effective preventing thrombosis, while being associated with little bleeding. Here, we...
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs). Central to the process switch vascular cells proliferative, apoptosis-resistant phenotype. Plasminogen activator inhibitors-1 -2 (PAI-1 PAI-2) are primary physiological inhibitors urokinase-type tissue-type plasminogen activators (uPA tPA), but their roles in PAH unsettled. Here, we report that:
Urokinase (uPA)- and urokinase receptor (uPAR)-dependent cell adhesion to the extracellular matrix protein vitronectin (Vn) is an important event in wound healing, tissue remodeling, immune response, cancer. We recently demonstrated that human vascular smooth muscle cells (VSMC) uPA/uPAR are functionally associated with ectoprotein kinase casein kinase-2 (CK2). now asked whether CK2 regulates uPA-dependent Vn, since latter a natural substrate. found Vn indeed selectively phosphorylated by...
uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, binding to the uPAR (uPA receptor; also known as CD87), integrins LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In present paper we report that uPA-mediated requires an interaction with fibulin-5. wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no...
N-methyl-D-aspartate (NMDA) receptors are widely expressed in the central nervous system. However, their presence and function at extraneuronal sites is less well characterized. In present study, we examined expression of NMDA receptor subunit mRNA protein human pulmonary artery (HPA) by quantitative polymerase chain reaction (PCR), immunohistochemistry immunoblotting. We demonstrate that both GluN1 GluN2 mRNAs HPA. addition, (A-D) proteins smooth muscle cells (HPASMCs) vitro vivo. These...
We defined the role of urokinase plasminogen activator (uPA) and its growth factor‐like domain (GFD) in stimulating smooth muscle cell (SMC) migration. Recombinant uPA (r‐uPA) stimulated migration approximately 3‐fold whilst recombinant mutant containing an altered GFD (r‐uPAmut) was ineffective. Both variants bound to same high affinity receptor a competitive manner. FGF‐2‐ PDGF‐BB‐induced also dependent on uPA, their effects being antagonized by addition uPA‐neutralizing antibody or...