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Fluorescent/magnetic nano-aggregation via electrostatic force between modified quantum dot and iron oxide nanoparticles for bimodal imaging of U87MG tumor cells.

Imaging technology based on novel nanomaterials is burgeoning as a potential tool for exploring various physiological processes. We herein report a fluorescent and magnetic nanoprobe (QMNP-RGD) for bimodal imaging of in vitro tumor cells. The preparation of this multifunctional nanomaterial is divided into three steps. First, commercial quantum dots (QDs) with high fluorescence intensity are covalently modified with an RGD peptide, which can facilitate the tumor cell uptake by αvβ3 integrin-induced active recognition. Superparamagnetic iron oxide (SPIO) nanoparticles (NPs) are then capped usin

RGD-Modified Titanium as an Improved Osteoinductive Biomaterial for Use in Dental and Orthopedic Implants.

This study describes the synthesis, surface analysis, and biological evaluation of bioactive titanium surfaces. The aim was to achieve an improved effect on osteoinduction in dental and orthopedic implants. For this purpose, a chemistry was developed, which allows to bind the bioactive cyclopeptide cRGDfK covalently to biomedically used titanium via polyethylene glycol linkers of different lengths. The chemical process is practicable, robust, and metal-free. The resulting chemically modified titanium plates show improved osteoinductive properties. The modification with cRGDfK targets the integ

Multimodal molecular imaging of atherosclerosis: Nanoparticles functionalized with scFv fragments of an anti-αIIbβ3 antibody.

Due to the wealth of actors involved in the development of atherosclerosis, molecular imaging based on the targeting of specific markers would substantiate the diagnosis of life-threatening atheroma plaques. To this end, TEG4 antibody is a promising candidate targeting the activated platelets (integrin αIIbβ3) highly represented within the plaque. In this study, scFv antibody fragments were used to functionalize multimodal imaging nanoparticles. This grafting was performed in a regio-selective way to preserve TEG4 activity and the avidity of the nanoparticles was studied with respect to the nu

Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells.

Phenotypic plasticity and subsequent generation of intratumoral heterogeneity underly key traits in malignant melanoma such as drug resistance and metastasis. Melanoma plasticity promotes a switch between proliferative and invasive phenotypes characterized by different transcriptional programs of which MITF is a critical regulator. Here, we show that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK

CD11b-deficient mice exhibit an increased severity in the late phase of antibody transfer-induced experimental epidermolysis bullosa acquisita.

CD11b, the α-chain of β2 integrin Mac-1, is involved in many activation processes of phagocytes. Depending on the respective autoimmune disorder, CD11b has been shown to exert pro-inflammatory functions or be dispensable in their pathogenesis. Here, we investigated the role of CD11b in the pathogenesis of experimental epidermolysis bullosa acquisita (EBA), an autoimmune skin blistering disease mediated by autoantibodies to type VII collagen. Unexpectedly, in an antibody transfer-induced model of EBA, CD11b-deficient mice developed more severe disease symptoms than wild-type mice in the late ph

Adenovirus sensing by the immune system.

The host immune system developed multiple ways for recognition of viral pathogens. Upon disseminated adenovirus infection, the immune system senses adenovirus invasion from the moment it enters the bloodstream. The soluble blood factors, FX, antibodies, and complement, can bind and activate plethora of host-protective immune responses. Adenovirus binding to the cellular β3 integrin and endosomal membrane rupture trigger activation of IL-1α/IL-1R1 proinflammatory cascade leading to attraction of cytotoxic immune cells to the site of infection. Upon cell entry, adenovirus exposes its DNA genome

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment.

Crohn's disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination the

Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucel

Requirement for core 2 O-glycans for optimal resistance to helminth infection.

The migration of lymphocytes to the small intestine is controlled by expression of the integrin α4β7 and the chemokine receptor CCR9. However, the molecules that specifically regulate migration to the large intestine remain unclear. Immunity to infection with the large intestinal helminth parasite Trichuris muris is dependent upon CD4(+) T cells that migrate to the large intestine. We examine the role of specific chemokine receptors, adhesion molecules and glycosyltransferases in the development of protective immunity to Trichuris. Mice deficient in expression of the chemokine receptors CCR2 o

Therapeutic targets for bone metastases in breast cancer.

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3

Совпадение в полном тексте источника
… There are several ongoing clinical trials evaluating the anticancer effect of integrin antagonists in advanced refractory and metastatic cancers [ 14 , 16 ]. Only a few integrin antagonists are being evaluated in breast cancer patients with bone metastasis (Table 1 ). … Syk, c-Src, the avb3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J Cell Biol. 2007;176:877–888. doi: 10.1083/jcb.200611083. Clézardin P. Integrins in bone metastasis formation and potential therapeutic implications. …

Pharmacological aspects of Vipera xantina palestinae venom.

In Israel, Vipera xantina palestinae (V.x.p.) is the most common venomous snake, accounting for several hundred cases of envenomation in humans and domestic animals every year, with a mortality rate of 0.5 to 2%. In this review we will briefly address the research developments relevant to our present understanding of the structure and function of V.x.p. venom with emphasis on venom disintegrins. Venom proteomics indicated the presence of four families of pharmacologically active compounds: (i) neurotoxins; (ii) hemorrhagins; (iii) angioneurin growth factors; and (iv) different types of integri…

A role for cell adhesion in beryllium-mediated lung disease.

Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between in

Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccha

Intercellular calcium communication regulates platelet aggregation and thrombus growth.

The ability of platelets to form stable adhesion contacts with other activated platelets (platelet cohesion or aggregation) at sites of vascular injury is essential for hemostasis and thrombosis. In this study, we have examined the mechanisms regulating cytosolic calcium flux during the development of platelet-platelet adhesion contacts under the influence of flow. An examination of platelet calcium flux during platelet aggregate formation in vitro demonstrated a key role for intercellular calcium communication (ICC) in regulating the recruitment of translocating platelets into developing aggr

Identification of sites in the cysteine-rich domain of the class P-III snake venom metalloproteinases responsible for inhibition of platelet function.

Atrolysin A and jararhagin are class P-III snake venom metalloproteinases (SVMPs) with three distinct domains: a metalloproteinase, a disintegrin-like and a cysteine-rich. The metalloproteinase and the disintegrin-like domains of atrolysin A and jararhagin contain peptide sequences that interact with alpha2beta1 integrin and inhibit the platelet responses to collagen. Recently, the recombinant cysteine-rich domain of atrolysin A was shown to have similar effects, but the sequence(s) responsible for this is unknown. In this report, we demonstrate two complete peptide sequences from the homologo

Трансгенная модель мыши для эховирусного миокардита и паралича.

Эховирусы были замешаны в многочисленных синдромах заболеваний человека, включая асептический менингит, паралич и сердечные заболевания, однако для изучения патогенеза инфекции нет ни одной модели животных. Производство человека интегрина очень поздний антигена 2, рецептора эховируса типа 1 в трансгенных мышах, придало восприимчивость к вирусной инфекции. Прививка новорожденных трансгенных мышей эховирусом в результате инфракрасных прививок приводит к параличу и растрачиванию. У инфицированных нетрансгенных мышей не было зарегистрировано никаких заболеваний. В парализованных мышах было отмечен

Radiolabeled peptides in the diagnosis and therapy of oncological diseases.

There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in oncology. Peptides have fast clearance, rapid tissue penetration, low antigenicity and can be produced easily and inexpensively. However, peptides have problems with in vivo catabolism, unwanted physiological effects, and chelate attachment. The approved 111In-DTPA-OctreoScan, a somatostatin receptor binder, is well established for diagnosis of neuroendocrine tumors. NeoTect, an approved, 99mTc-labeled, somatostatin-receptor-binding analogue has good specificity for l

Enrichment and transplantation of spermatogonial stem cells.

Spermatogenesis is a complex, highly organized process originated from stem cell spermatogonia. Because there are very few stem cells and they can only be defined by their function, the identification and isolation of these cells has been very difficult. By using a spermatogonial transplantation assay system, we have identified alpha6-and beta1-integrin expression on stem cells, and cells isolated with these antigens were significantly enriched in stem cells. This is the first demonstration of spermatogonial stem cell-associated antigens. Analysis of two infertile mouse models, Steel/SteelDick

Hemidesmosomes and their unique transmembrane protein BP180.

Hemidesmosomes are adhesion complexes responsible for linking keratin intermediate filaments of stratified and complex epithelia to components of the extracellular matrix such as collagen fibrils. Over the past several years, it has become clear that there are at least five hemidesmosomal proteins, including HD1/plectin and BP230 as cytoplasmic plaque proteins and integrin alpha6beta4 and BP180 as transmembrane proteins. Among them, BP180 is unique as a transmembrane protein because of its collagenous extracellular domain. Recent biochemical and ultrastructural analyses have revealed its molec

Multinucleated giant cell formation of swine microglia induced by Mycobacterium bovis.

Multinucleated giant cells (MGC) have been long recognized as a histopathologic feature of tuberculosis, yet little is known about the underlying mechanism of tubercle bacillus-induced formation of these fused macrophages. The main purpose of this study was to characterize cellular mechanisms involved in MGC formation of swine microglia, the resident macrophages of the brain, in cultures containing nonopsonized Mycobacterium bovis. Within 2 h of incubation, MGC were readily detected in these cultures by light and transmission electron microscopy. MGC formation was blocked by anti-CD14 and anti