Avb3

BACKGROUND: Integrin αvβ3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)-when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction-may enhance cellular uptke of SARS-CoV-2 and its receptor...

BACKGROUND: Complete atrioventricular block (AVB3) may be an urgent potentially lifethreatening situation. Our objective was to describe the routine management of AVB 3, with emphasis on the organizational aspects. METHODS: From September 2019 to November 2019, a prospective national survey including 28 questions was electronically sent to 100 physicians (Google Form). RESULTS: The answers were collected from 93 physicians (response rate 93%)...

Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identification of non-RGD hit small-molecule αvβ1 inhibitors. We show that αvβ1 activity is embedded in a range of published α4β1 (VLA-4) ligands; we also demonstrate how a non-RGD integrin inhibitor (of α4β1 in this case) was converted into a potent non-zwitterionic RGD integrin inhibitor (of αvβ1 in this case)...

Implantation failure is a major problem in human assisted reproduction, which persists regardless the optimization of endometrial receptivity and selection of genetically and morphologically healthy embryos. Since embryo-endometrium interaction depends on cell junctional, cell adhesion and cell-substratum adhesion molecules, the present study inquired whether in vitro growing murine embryos display similar to the in vivo growing embryos patterns of adhesion molecules. To this extend aVb3 expression and distribution in zygotes and 2-cell stage embryos were studied...

Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels...

HPMA copolymer-RGDfK (HPMA-RGDfK) conjugates bearing either aminohexylgeldanamycin (AHGDM) or docetaxel (DOC) were synthesized and characterized. In vitro stability and binding were evaluated. Cytotoxicity toward ovarian cancer cells was evaluated and the ability of the conjugates to induce cell death was assessed by combination index analysis. Conjugates bearing AHGDM were more stable and exhibited slower drug release than those bearing DOC. Both conjugates demonstrated the ability to bind to avb3 integrins...

BACKGROUND: Intracoronary Abciximab administration during primary percutaneous coronary intervention (pPCI) could offer theoretical advantages over the intravenous route. Besides antiplatelet effects, Abciximab can modulate inflammation via cross-reactivity with GPIIb/IIIa, avb3, and aMb2 receptors. The aim of our study was to assess whether the Abciximab administration route could influence its anti-inflammatory effects. METHODS: Eighty-nine consecutive ST elevation myocardial infarction patient candidates for pPCI were randomized to intracoronary (Group A-47 patients) or intravenous (Group B-42 patients) Abciximab bolus administration...

TGFBI, a transforming growth factor β-induced extracellular matrix protein, circulates at a level of ~300ng/ml in humans and modulates several integrin-mediated cellular functions. The protein contains an N-terminal EMI domain, four consecutive FAS1 domains, and the RGD motif. Each FAS1 domain and the RGD motif have been known to interact with avb3 integrin. Here, we found that the binding affinity (Kd) of TGFBI for αvβ3 integrin was approximately 3.8×10(-8)M, a value ~2300-fold higher than that of a single FAS1 domain, and demonstrated that this greater affinity was due to the cooperative action of the four FAS1 domains and the RGD motif...

INTRODUCTION: Osteoarthritis (OA) is the most common degenerative joint disease that is involved in the degradation of articular cartilage. The exact etiology of OA is not completely understood. CCN4 is related to up-regulation in the cartilage of patients with osteoarthritis. Previous studies have shown that CCN4 might be associated with the pathogenesis of OA, but the exact signaling pathways in CCN4-mediated IL-6 expression in synovial fibroblasts (SF) are largely unknown. Therefore, we explored the intracellular signaling pathway involved in CCN4-induced IL-6 production in human synovial fibroblast cells...

INTRODUCTION: The RAS/RAF/MEK/ERK signaling pathway plays an important role in osteoclast (OC) differentiation and survival mediated by macrophage-colony stimulating factor (M-CSF). Also, vascular endothelial growth factor (VEGF) may greatly influence OC formation and resorption through VEGFR1 and VEGFR2. RAF265 is a novel, orally bioavailable dual inhibitor of RAF kinase and VEGFR2. METHODS: Effect of RAF265 on osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) and OC resorption on calcium-coated wells was assessed by appropriate in vitro assays...

Low level, antenatal exposure to dioxins is associated with low birth weight, which in turn is associated with long-term sequelae. We exposed the human extravillous cytotrophoblast (EVT) lines HTR-8/SV40 and TCL1 to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and assessed cell growth, invasion, and differentiation. TCDD had no effect on cell proliferation, invasion, or tube formation in Matrigel. The EVT-derived cells expressed a functional aryl hydrocarbon receptor protein; however, TCDD exposure did not alter expression levels of proteins involved in EVT differentiation in early pregnancy, including hypoxia-inducible factor 1A (HIF1A), vascular endothelial growth factor (VEGF), Integrin A1, A6, and AVB3...

BACKGROUND: Bisphosphonates are therapeutics of bone diseases, such as Paget's disease, multiple myeloma or osteoclastic metastases. As a severe side effect the bisphosphonate induced osteonecrosis of the jaw (BONJ) often requires surgical treatment and is accompanied with a disturbed wound healing.Therefore, the influence on adhesion and migration of human osteoblasts (hOB) after bisphosphonate therapy has been investigated by morphologic as well as gene expression methods. METHODS: By a scratch wound experiment, which measures the reduction of defined cell layer gap, the morphology and migration ability of hOB was evaluated...

Angiogenesis, a course that new blood vessels grow from the existing vasculature, plays important roles both physiologically and pathologically. Angiogenesis can be switched on by growth factors secreted by tumor cells, and in turn supplies more oxygen and nutrition to the tumor. More and more preclinical studies and clinical trials have shown that inhibition of angiogenesis is an effective way to inhibit tumor growth, substantiating the development of anti-angiogenesis therapeutics. Imaging technologies accelerate the translation of preclinical research to the clinic...

Angiogenesis, the formation of new blood vessels, is a key process in the growth of solid tumors. Thus this process could potentially be utilized for diagnosis of malignancies by molecular imaging on the one hand and for tumor treatment on the other hand. Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies, like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting e.g. for response assessment of such targeted antiangiogenic therapies...

The World Health Organization (WHO) declared osteoporosis "social disease". The present revision of the literature will focus on the recent acquisitions in bone pathophysiology and the efforts in the formulation of new molecules able to change successfully the course of the disease. Osteocyte cell is now thought to be the main biomechanical transducer of bones, able to release sclerostin that produces inhibition on osteosynthesis and on the other hand to release substances like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis through direct or indirect activation of osteoblasts...

Stimulatiion of coronary angiogenesis in patients with IHD appears to be one of perspective directions in contemporary cardiology. Therefore objective assessment of results with the help of instrumental methods of investigation is important. For assessment of the state of coronary vascular bed and myocardial perfusion in the clinic one can use coronarography, single photon emission computer tomography, positron emission tomography, magnetic resonance tomography, and contrast echocardiography. Novel techniques of visualization are elaborated at present with consideration of peculiarities of mechanisms and use of molecular markers of angiogenesis: visualization of integrin avb3, VEGF-receptors, visualization of activity of matrix metalloproteinases...

Living organisms, from bacteria to vertebrates, are well known to generate sophisticated multicellular patterns. Numerous recent interdisciplinary studies have focused on the formation and regulation of these structures. Advances in automatized microscopy allow the time-resolved tracking of embryonic development at cellular resolution over an extended area covering most of the embryo. The resulting images yield simultaneous information on the motion of multiple tissue components-both cells and extracellular matrix (ECM) fibers...

The platelet glycoprotein (GP) IIb/IIIa inhibitors differ markedly in their pharmacokinetics, pharmacodynamics, and differential receptor affinities. Abciximab and the small-molecule GP IIb/IIIa inhibitors (eptifibatide, tirofiban) have separate, distinct binding sites on the GP IIb/IIIa receptor complex. The affinity of abciximab for the platelet GP IIb/IIIa integrin receptor, together with non-platelet-receptor mediated effects achieved through its affinity for the aVb3 and CD11b/18 receptors, most likely contribute to the clinical benefit associated with the use of abciximab as adjunctive pharmacotherapy during primary percutaneous coronary intervention for the treatment of ST-elevation acute myocardial infarction...

AIM: Our laboratory has recently demonstrated the pro-angiogenesis effects of thyroid hormone in the chick chorioallantoic membrane model. METHODS: Generation of new blood vessels from existing vessels was promoted two- to three-fold by either L-thyroxine (T4) or 3,5,3'-triiodo-L-thyronine (T3) at total hormone concentrations of T7-T9 M. RESULTS: T4-agarose, a formulation of thyroid hormone that does not cross the cell membrane, produced a potent pro-angiogenesis effect comparable to that obtained with T3 or T4...

OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic despite drug-eluting stents (DES), especially in diabetic patients and in those with small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both thrombosis and proliferation. The aim of the present studies was to examine the absorption and elution characteristics of eptifibatide on polymer-coated stents and investigated their effect on SMC proliferation, platelet deposition and platelet aggregation in vitro...