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https://www.readbyqxmd.com/read/28819560/a-novel-peptide-blocking-cancer-cell-invasion-by-structure-based-drug-design
#1
Yuki Yamada, Seiji Kanayama, Fuminori Ito, Noriyuki Kurita, Hiroshi Kobayashi
The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28814715/mast-cells-decrease-efficacy-of-anti-angiogenic-therapy-by-secreting-matrix-degrading-granzyme-b
#2
M Wroblewski, R Bauer, M Cubas Córdova, F Udonta, I Ben-Batalla, K Legler, C Hauser, J Egberts, M Janning, J Velthaus, C Schulze, K Pantel, C Bokemeyer, S Loges
Resistance towards VEGF-centered anti-angiogenic therapy still represents a substantial clinical challenge. We report here that mast cells alter the proliferative and organizational state of endothelial cells which reduces the efficacy of anti-angiogenic therapy. Consequently, absence of mast cells sensitizes tumor vessels for anti-angiogenic therapy in different tumor models. Mechanistically, anti-angiogenic therapy only initially reduces tumor vessel proliferation, however, this treatment effect was abrogated over time as a result of mast cell-mediated restimulation of angiogenesis...
August 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28790378/hypoxia-impairs-agonist-induced-integrin-%C3%AE-iib%C3%AE-3-activation-and-platelet-aggregation
#3
Klytaimnistra Kiouptsi, Stepan Gambaryan, Elena Walter, Ulrich Walter, Kerstin Jurk, Christoph Reinhardt
Under ischemic conditions, tissues are exposed to hypoxia. Although human physiology, to a certain extent, can adapt to hypoxic conditions, the impact of low oxygen levels on platelet function is unresolved. Therefore, we explored how reduction of atmospheric oxygen levels to 1% might affect agonist-induced aggregation and static adhesion of isolated human platelets. We uncovered that isolated, washed human platelets exposed to hypoxic conditions show reduced thrombin receptor-activating peptide-6 (TRAP-6) and convulxin-induced aggregation...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28776905/expression-of-cytokine-and-extracellular-matrix-mrnas-in-fetal-hepatic-stellate-cells
#4
Keai Sinn Tan, Kasem Kulkeaw, Yoichi Nakanishi, Daisuke Sugiyama
In mouse fetal liver, hepatoblasts, sinusoidal endothelial cells and macrophages (or erythroblastic islands) promote differentiation and proliferation of hematopoietic cells through cell-cell interactions and secretion of cytokines and extracellular matrix factors. Until now, we have had little knowledge of the hematopoietic cytokines or extracellular matrix mRNAs expressed in hepatic stellate cells. Using p75 neurotrophin receptor (p75NTR) to mark this cell population, we sorted 12.5, 14.5 and 16.5 dpc hepatic stellate cells and analyzed expression of cytokines and extracellular matrix mRNAs...
August 4, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28773852/design-of-decorated-self-assembling-peptide-hydrogels-as-architecture-for-mesenchymal-stem-cells
#5
Annj Zamuner, Marta Cavo, Silvia Scaglione, Grazia Maria Lucia Messina, Teresa Russo, Antonio Gloria, Giovanni Marletta, Monica Dettin
Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D "architecture" for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK) and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP) motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1)...
August 26, 2016: Materials
https://www.readbyqxmd.com/read/28763481/osteoclastic-differentiation-and-resorption-is-modulated-by-bioactive-metal-ions-co2-cu2-and-cr3-incorporated-into-calcium-phosphate-bone-cements
#6
Anne Bernhardt, Martha Schamel, Uwe Gbureck, Michael Gelinsky
Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined. Human osteoclasts were differentiated from human peripheral blood mononuclear cells (PBMC) both on the surface and in indirect contact to the materials on dentin discs...
2017: PloS One
https://www.readbyqxmd.com/read/28754556/kidney-function-is-associated-with-an-altered-protein-composition-of-high-density-lipoprotein
#7
Katya B Rubinow, Clark M Henderson, Cassianne Robinson-Cohen, Jonathan Himmelfarb, Ian H de Boer, Tomas Vaisar, Bryan Kestenbaum, Andrew N Hoofnagle
Patients with chronic kidney disease (CKD) exhibit a myriad of metabolic derangements, including dyslipidemia characterized by low plasma concentrations of high-density lipoprotein (HDL)-associated cholesterol. However, the effects of kidney disease on HDL composition have not been comprehensively determined. Here we used a targeted mass spectrometric approach to quantify 38 proteins contained in the HDL particles within a CKD cohort of 509 participants with a broad range of estimated glomerular filtration rates (eGFRs) (CKD stages I-V, and a mean eGFR of 45...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28743114/cervical-alpha-actinin-4-is-upregulated-in-women-with-threatened-preterm-labor-and-microbial-invasion-of-the-amniotic-cavity
#8
Teresa Cobo, Montse Palacio, Maribel Grande, Ana B Sánchez-García, Josep M Estanyol, Marta López, Jordi Bosch, Cristina Martí, Eduard Gratacós
OBJECTIVE: To characterize the proteome profile of women with threatened preterm labor (PTL) below 34;0 weeks with and without microbial invasion of the amniotic cavity (MIAC) using mass spectrometry in the amniotic fluid (AF) and Western blot analysis in the cervical mucus and the vaginal fluid. SUBJECTS AND METHODS: In the discovery phase, a case-control study including 8 women with MIAC and 7 without matched for gestational age at sampling was performed. Proteomic profile characterization was done using the LTQ VELOS Orbitrap mass spectrometer in the AF...
July 26, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28738206/a-preliminary-study-on-the-effects-of-lanthanum-iii-on-plant-vitronectin-like-protein-and-its-toxicological-basis
#9
Lihong Wang, Jingfang He, Qing Yang, Xiaodong Li, Haiyan Wei, David D Y Chen, Xiaohua Huang
Vitronectin-like protein (VN) is widely found outside plant plasma membranes. The VN molecular surface contains a large number of active groups that combine strongly with rare earth elements (REEs), which means that VN is a preferential binding target for REEs exhibiting their toxic effects, but the toxicological mechanism remains unknown. This study used transmission electron microscopy, circular dichroism, fluorescence spectrometry, ultraviolet-visible spectroscopy, X-ray photoelectron spectroscopy, and calculational chemistry (homology modeling, molecular dynamics simulation and quantum chemical calculation) to preliminarily investigate the effect of lanthanum [La(III)] as an REE, on the structure of VN and its toxicological mechanism...
July 21, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28720870/monocyte-adhesion-to-atherosclerotic-matrix-proteins-is-enhanced-by-asn-gly-arg-deamidation
#10
Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683586/vitronectin-regulates-the-fibrinolytic-system-during-the-repair-of-cerebral-cortex-in-stab-wounded-mice
#11
Kei Hashimoto, Natsumi Ikeda, Mari Nakashima, Hiroko Ikeshima-Kataoka, Yasunori Miyamoto
Vitronectin (VN), one of the serum proteins, is known to be involved in the regulation of blood coagulation, fibrinolysis, and cell migration. It has been proposed that the regulation of fibrinolysis by VN promotes the blood-brain barrier (BBB) recovery from brain injuries such as traumatic injury and subarachnoid hemorrhage. The effects of VN on fibrinolysis in the injured brain remain unclear, however. We examined the effects of VN on the fibrinolytic system in the stab-wounded cerebral cortex of VN-knockout (KO) mice...
August 7, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28679987/analysis-of-deposited-peptides-in-amyloid-lesions-of-al-amyloidosis-by-mass-spectrometry
#12
Toshiya Sugimoto, Masayoshi Tasaki, Taro Yamashita, Mitsuharu Ueda, Yukio Ando, Konen Obayashi, Yutaka Okuno, Hiroyuki Hata
Although immunoglobulin light chain (LC) plays a critical role in AL amyloidosis, detailed characteristics of deposited LC are not well known. In this study, LC peptides were analyzed by a combination of laser microdissection, liquid chromatography, and mass spectrometry (LC-MS/MS) in 65 patients with AL amyloidosis. Constant regions of LC were detected in all patients. Kappa- or lambda-types were detected in 20 and 45 patients, respectively. Various types of constant regions of LC were found; however, IGLC3 and IGKC4 were the most frequently detected...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28679024/multi-pronged-proteomic-analysis-to-study-the-glioma-pathobiology-using-cerebrospinal-fluid-samples
#13
Nikita Gahoi, Darpan Malhotra, Aliasgar Moiyadi, Santosh G Varma, Mayuri N Gandhi, Sanjeeva Srivastava
PURPOSE: Gliomas are one of the most aggressive and lethal brain tumors arising from neoplastic transformation of astrocytes and oligodendrocytes. In this study, we have carried out a comprehensive quantitative analysis of proteome level differences in cerebrospinal fluid (CSF) across different grades of gliomas for a better understanding of glioma pathobiology. EXPERIMENTAL DESIGN: Glioma patients were diagnosed by radiology and histochemistry- based analyses. Differential proteomic analysis of high (n = 12) and low (n = 8) grade gliomas, and control (n = 3) samples was performed by using two complementary quantitative proteomic approaches; 2D-DIGE and iTRAQ...
July 5, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28676664/itraq-based-quantitative-proteomic-analysis-of-the-inhibitory-effects-of-polysaccharides-from-viscum-coloratum-kom-nakai-on-hepg2-cells
#14
Yangyang Chai, Min Zhao
Viscum coloratum (Kom.) Nakai is one of active medicinal plants, and its active components, especially polysaccharides, have been shown to exhibit bioactivity. In this study, we examined the effects of three polysaccharide fractions from Viscum coloratum (Kom.) Nakai on HepG2 cell growth in a dose-dependent manner by using a CCK-8 assay kit. Flow cytometry analysis showed that VCP2 treatment delayed the cell cycle in the G1 phase and induced apoptosis in HepG2 cells, a result possibly due to the increased expression of p21(Wafl/Cip1) and Cyclin D and the decreased expression of Cyclin E and CDK4...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28666984/the-nuclear-receptor-nor-1-nr4a3-regulates-the-multifunctional-glycoprotein-vitronectin-in-human-vascular-smooth-muscle-cells
#15
Ingrid Martí-Pàmies, Laia Cañes, Judith Alonso, Cristina Rodríguez, José Martínez-González
The nuclear receptor NOR-1 (NR4A3) has recently been involved in the regulation of extracellular matrix (ECM) proteins associated with neointimal thickening and the vascular control of hemostasis. We sought to find as-yet unidentified NOR-1 target genes in human vascular smooth muscle cells (VSMCs). An in silico analysis identified putative NOR-1 response elements in the proximal promoter region of several genes encoding for ECM proteins including vitronectin (VTN). Lentiviral overexpression of NOR-1 strongly increased VTN mRNA and protein levels, whereas NOR-1 silencing significantly reduced VTN expression...
June 30, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28662039/expression-of-rickettsia-adr2-protein-in-e-coli-is-sufficient-to-promote-resistance-to-complement-mediated-killing-but-not-adherence-to-mammalian-cells
#16
Daniel A Garza, Sean P Riley, Juan J Martinez
Bacteria exposed to host serum are subject to the antibacterial effects to the complement system. However, pathogenic microorganisms have evolved mechanisms of evading this immune attack. We have previously demonstrated that at least two R. conorii antigens, RC1281/Adr1 and OmpB β-peptide, contribute to the evasion of complement-mediated killing by binding the complement regulatory proteins vitronectin and factor H. RC1282/Adr2, a protein related to Adr1, is predicted to share similar structural features, suggesting that this protein may also contribute to evasion of complement-mediated killing...
2017: PloS One
https://www.readbyqxmd.com/read/28659710/fluid-shear-stress-and-fibroblast-growth-factor-2-increase-endothelial-cell-associated-vitronectin
#17
Justin G Mathew, Sarah Basehore, Alisa Morss Clyne
Vitronectin is a matricellular protein that plays an important role in both coagulation and angiogenesis through its effects on cell adhesion and the plasminogen system. Vitronectin is known to bind to endothelial cells upon integrin activation. However, the effect of integrin activation by shear stress and growth factors on cell-associated vitronectin and plasminogen system activity has not yet been studied. We therefore exposed human umbilical vein endothelial cells to steady laminar flow, oscillating disturbed flow, or fibroblast growth factor-2 (FGF-2) for 24 hours...
2017: Applied Bionics and Biomechanics
https://www.readbyqxmd.com/read/28640945/production-of-human-vitronectin-in-nicotiana-benthamiana-using-the-inpact-hyper-expression-platform
#18
Benjamin Dugdale, Maiko Kato, Pradeep Deo, Manuel Plan, Mark Harrison, Robyn Lloyd, Terry Walsh, Robert Harding, James Dale
Human vitronectin (hVN) is a glycoprotein that functions as a cell adhesion molecule and a regulator of coagulation in blood plasma and the extracellular matrix. In vitro, hVN is added to serum-free media in order to promote the adhesion of animal cells to tissue culture surfaces and the proliferation of undifferentiated stem cells. Here, we report the production of hVN in Nicotiana benthamiana using the inducible In Plant Activation (INPACT) hyper-expression platform. N. benthamiana plants were transformed with an INPACT expression cassette encoding hVN, and both the Tobacco yellow dwarf virus Rep/RepA activator and Tomato bushy stunt virus p19 gene under the transcriptional control of the ethanol-inducible AlcR:alcA gene switch...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28621746/biocompatibility-analyses-of-al%C3%A2-o%C3%A2-treated-titanium-plates-tested-with-osteocyte-and-fibroblast-cell-lines
#19
Alberto Smargiassi, Jessika Bertacchini, Marta Checchi, Francesco Cavani, Marzia Ferretti, Carla Palumbo
Osseointegration of a titanium implant is still an issue in dental/orthopedic implants durable over time. The good integration of these implants is mainly due to their surface and topography. We obtained an innovative titanium surface by shooting different-in-size particles of Al₂O₃ against the titanium scaffolds which seems to be ideal for bone integration. To corroborate that, we used two different cell lines: MLO-Y4 (murine osteocytes) and 293 (human fibroblasts) and tested the titanium scaffolds untreated and treated (i...
June 16, 2017: Biomedicines
https://www.readbyqxmd.com/read/28580316/interactome-mapping-guided-by-tissue-specific-phosphorylation-in-age-related-macular-degeneration
#20
Srinivas R Sripathi, Weilue He, Cameron L Prigge, O'Donnell Sylvester, Ji-Yeon Um, Folami L Powell, Musa Neksumi, Paul S Bernstein, Dong-Won Choo, Manuela Bartoli, Diana R Gutsaeva, Wan Jin Jahng
The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs...
February 2017: International Journal of Scientific and Engineering Research
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