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F Ravanetti, F Gazza, D D'Arrigo, G Graiani, A Zamuner, M Zedda, E Manfredi, M Dettin, A Cacchioli
Osteoblast cell adhesion to the extracellular matrix is established through two main pathways: one is mediated by the binding between integrin and a minimal adhesion sequence (RGD) on the extracellular protein, the other is based on the interactions between transmembrane proteoglycans and heparin-binding sequences found in many matrix proteins. The aim of this study is the evaluation in an in vivo endosseous implant model of the early osteogenic response of the peri-implant bone to a biomimetic titanium surface functionalized with the retro-inverso 2DHVP peptide, an analogue of Vitronectin heparin binding site...
April 18, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Lorenzo Sernissi, Luciano Ricci, Dina Scarpi, Francesca Bianchini, Daniela Arosio, Alessandro Contini, Ernesto G Occhiato
A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for binding with the isolated αVβ3 integrin was measured (IC50 = 4.2 ± 0.9 nM). A complete 1H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with cilengitide...
April 20, 2018: Organic & Biomolecular Chemistry
Saskia Roesch, Thomas Lindner, Max Sauter, Anastasia Loktev, Paul Flechsig, Martin Müller, Walter Mier, Rolf Warta, Gerhard Dyckhoff, Christel Herold-Mende, Uwe Haberkorn, Annette Altmann
Alpha v beta 6 (αvβ6) integrin is overexpressed by several carcinomas, and thus considered as target for diagnostic imaging and anti-cancer therapies. Recently, we presented SFITGv6 as a novel potential tracer for imaging and targeted therapy of αvβ6 integin-positive carcinomas. Here, we analyzed affinity and specificity of five native αvβ6 integrin-specific binders in comparison to SFITGv6. Methods: Sunflower trypsin inhibitor (SFTI)-1-based peptides containing arginine-glycine-aspartic acid (RGD) motif-spanning octamers of fibronectin (SFFN1), tenascin C (SFTNC), vitronectin (SFVTN), and latency-associated peptides (LAP) 1 (SFLAP1), and 3 (SFLAP3) were synthesized and their binding potential to αvβ6 integrin-expressing head and neck squamous cell carcinoma (HNSCC) cell lines was evaluated...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Tian-Le Shen, Mi-Na Liu, Qin Zhang, Wen Feng, Wen Yu, Xiao-Long Fu, Xu-Wei Cai
BACKGROUND: Radiation-induced lung toxicity (RILT) is a severe complication of radiotherapy in patients with thoracic tumors. Through proteomics, we have previously identified vitronectin (VTN) as a potential biomarker for patients with lung toxicity of grade ≥ 2 radiation. Herein, we explored the molecular mechanism of VTN in the process of RILT. METHODS: In this study, lentivirus encoding for VTN and VTN-specific siRNA were constructed and transfected into the cultured fibroblasts and C57BL mice...
April 16, 2018: Journal of Translational Medicine
Mengzhu Cheng, Lihong Wang, Qing Yang, Xiaohua Huang
The pollution of rare earth elements (REEs) in ecosystem is becoming more and more serious, so it is urgent to establish methods for monitoring the pollution of REEs. Monitoring environmental pollution via the response of plants to pollutants has become the most stable and accurate method compared with traditional methods, but scientists still need to find the primary response of plants to pollutants to improve the sensitivity and speed of this method. Based on the facts that the initiation of endocytosis is the primary cellular response of the plant leaf cells to REEs and the detection of endocytosis is complex and expensive, we constructed a detection method in living plant cells for rapidly monitoring the response of plants to exogenous lanthanum [La(III), a representative of REEs] by designing a new immuno-electrochemical method for detecting the content change in extracellular vitronectin-like protein (VN) that are closely related to endocytosis...
April 13, 2018: Ecotoxicology and Environmental Safety
Julius Mueller, Johanna Simon, Philipp Rohne, Claudia Koch-Brandt, Volker Mailaender, Svenja Morsbach, Katharina Landfester
The use of nanocarriers as drug delivery vehicles brings them into contact with blood plasma proteins. Polymeric nanocarriers require some sort of surfactant to ensure colloidal stability. Formation of the protein corona is therefore not only determined by the intrinsic properties of the nanocarrier itself, but also by the accompanying surfactant. Although it is well known that surfactants have an impact on protein structure, only few studies were conducted on the specific effect of surfactants on the composition of protein corona of nanocarriers...
April 16, 2018: Biomacromolecules
Caroline Amalie Brunbjerg Hey, Katarina Beata Saltoõkova, Hanne Cathrine Bisgaard, Lisbeth Birk Møller
Different culture-systems for derivation of induced pluripotent stem cells (iPSC) in vitro from human fibroblasts have been established. Here we compared the efficacy of two different feeder-free culture-systems; Matrigel-coated surfaces in combination with mTeSR1 medium versus Vitronectin-coated surfaces in combination with Essential 8 (E8) medium. The comparison was performed by counting the number of emerging iPSC-looking colonies of re-programmed fibroblasts. The fibroblasts were re-programmed using episomal plasmids expressing OCT3/4, SOX2, KLF4, L-MYC, LIN28 and a p53 knock down shP53...
March 30, 2018: Cell Biology International
Andrew Smith, Manuel Galli, Isabella Piga, Vanna Denti, Martina Stella, Clizia Chinello, Nicola Fusco, Davide Leni, Marco Manzoni, Gaia Roversi, Mattia Garancini, Angela Ida Pincelli, Vincenzo Cimino, Giulia Capitoli, Fulvio Magni, Fabio Pagni
The main aim of the study was to assess the feasibility of matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in the pathological investigation of Medullary Thyroid Carcinoma (MTC). Formalin-fixed paraffin-embedded (FFPE) samples from seven MTC patients were analysed by MALDI-MSI in order to detect proteomic alterations within tumour lesions and to define the molecular profiles of specific findings, such as amyloid deposition and C cell hyperplasia (CCH). nLC-ESI MS/MS was employed for the identification of amyloid components and to select alternative proteomic markers of MTC pathogenesis...
March 24, 2018: Journal of Proteomics
Raj Poovindran Anada, Kum Thong Wong, Jaime Jacqueline Jayapalan, Onn Haji Hashim, Dharmendra Ganesan
The Glasgow Coma Scale (GCS), which classifies patients into mild, moderate or severe traumatic brain injury (TBI), is a system used to prioritize treatment and prognosticate the severity of head injury. In this study, sera of patients with various stages of TBI, as well as control subjects, were analyzed to screen for proteins that may be used to complement the GCS system. By subjecting pooled serum samples to iTRAQ analysis for quantitative comparison of protein abundance, and attesting their altered levels using ELISA, we have detected increased levels of serum amyloid A, C-reactive protein, leucine-rich alpha-2-glycoprotein, lipopolysaccharide-binding protein, fibronectin, vitronectin and alpha-1-antichymotrypsin in patients across all strata of TBI relative to the controls...
March 23, 2018: Electrophoresis
Takahiro Tougan, Jyotheeswara R Edula, Eizo Takashima, Masayuki Morita, Miki Shinohara, Akira Shinohara, Takafumi Tsuboi, Toshihiro Horii
The malaria parasite Plasmodium falciparum proliferates in the blood stream where the host immune system is most active. To escape from host immunity, P. falciparum has developed a number of evasion mechanisms. Serine repeat antigen 5 (SERA5) is a blood stage antigen highly expressed at late trophozoite and schizont stages. The P47 N-terminal domain of SERA5, the basis of SE36 antigen of the blood stage vaccine candidate under clinical trials, covers the merozoite surface. Exploring the role of the P47 domain, screening of serum proteins showed that vitronectin (VTN) directly binds to 20 residues in the C-terminal region of SE36...
March 22, 2018: Scientific Reports
Kai Yu, Paula Andruschak, Han Hung Yeh, Dana Grecov, Jayachandran N Kizhakkedathu
The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich plasma and whole blood on three highly hydrophilic antifouling polymer brushes, (poly(N, N-dimethylacrylamide) (PDMA), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) using an in vitro blood loop model at comparable arterial and venous flow, and static conditions...
March 8, 2018: Biomaterials
Lizeth Bodero, Paula López Rivas, Barbara Korsak, Torsten Hechler, Andreas Pahl, Christoph Müller, Daniela Arosio, Luca Pignataro, Cesare Gennari, Umberto Piarulli
RGD-α-amanitin and isoDGR-α-amanitin conjugates were synthesized by joining integrin ligands to α-amanitin via various linkers and spacers. The conjugates were evaluated for their ability to inhibit biotinylated vitronectin binding to the purified αV β3 receptor, retaining good binding affinity, in the same nanomolar range as the free ligands. The antiproliferative activity of the conjugates was evaluated in three cell lines possessing different levels of αV β3 integrin expression: human glioblastoma U87 (αV β3 +), human lung carcinoma A549 (αV β3 -) and breast adenocarcinoma MDA-MB-468 (αV β3 -)...
2018: Beilstein Journal of Organic Chemistry
Marco Cantini, Karina Gomide, Vladimira Moulisova, Cristina González-García, Manuel Salmerón-Sánchez
Surface functionalization strategies of synthetic materials for regenerative medicine applications comprise the development of microenvironments that recapitulate the physical and biochemical cues of physiological extracellular matrices. In this context, material-driven fibronectin (FN) nanonetworks obtained from the adsorption of the protein on poly(ethyl acrylate) provide a robust system to control cell behavior, particularly to enhance differentiation. This study aims at augmenting the complexity of these fibrillar matrices by introducing vitronectin, a lower-molecular-weight multifunctional glycoprotein and main adhesive component of serum...
September 2017: Advanced Biosystems
Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight
Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis...
February 20, 2018: International Journal of Biochemistry & Cell Biology
Maria Del Ben, Diletta Overi, Licia Polimeni, Guido Carpino, Giancarlo Labbadia, Francesco Baratta, Daniele Pastori, Valeria Noce, Eugenio Gaudio, Francesco Angelico, Carmine Mancone
Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients...
February 18, 2018: International Journal of Molecular Sciences
Junfeng Ma, Miloslav Sanda, Renhuizi Wei, Lihua Zhang, Radoslav Goldman
Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow...
February 7, 2018: Journal of Proteomics
Xuefeng Yuan, Alexandre Caron, Hua Wu, Laurent Gautron
Past studies have suggested that non-neuronal brain cells express the leptin receptor. However, the identity and distribution of these leptin receptor-expressing non-neuronal brain cells remain debated. This study assessed the distribution of the long form of the leptin receptor (LepRb) in non-neuronal brain cells using a reporter mouse model in which LepRb-expressing cells are permanently marked by tdTomato fluorescent protein (LepRb-CretdTomato ). Double immunohistochemistry revealed that, in agreement with the literature, the vast majority of tdTomato-tagged cells across the mouse brain were neurons (i...
2018: Frontiers in Neuroanatomy
Eric S Orwoll, Jack Wiedrick, Jon Jacobs, Erin S Baker, Paul Piehowski, Vladislav Petyuk, Yuqian Gao, Tujin Shi, Richard D Smith, Douglas C Bauer, Steven R Cummings, Carrie M Nielson, Jodi Lapidus
The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire...
February 5, 2018: Aging Cell
Chandni Porayath, Maneesha K Suresh, Raja Biswas, Bipin G Nair, Nandita Mishra, Sanjay Pal
Major autolysin (Atl) of Staphylococcus aureusis a cell surface associated peptidoglycan hydrolase with amidase and glucosaminidase domains. Atl enzymes (amidase and glucosaminidase) are known to participate in biofilm formation and also can bind with host matrices. Earlier studies demonstrated the binding of Atlwithfibronectin, thrombospondin 1, vitronectin and heat shock cognate protein Hsc70. Here, we have shown, Atl mediates attachment of S.aureus to heparin and gelatine as well. The atl mutant strain demonstrated around 2...
February 2, 2018: International Journal of Biological Macromolecules
Matthew G Annis, Veronique Ouellet, Jonathan P Rennhack, Sylvain L'Esperance, Claudine Rancourt, Anne-Marie Mes-Masson, Eran R Andrechek, Peter M Siegel
BACKGROUND: The Fos-related antigen 1 (FRA-1) transcription factor promotes tumor cell growth, invasion and metastasis. Phosphorylation of FRA-1 increases protein stability and function. We identify a novel signaling axis that leads to increased phosphorylation of FRA-1, increased extracellular matrix (ECM)-induced breast cancer cell invasion and is prognostic of poor outcome in patients with breast cancer. METHODS: While characterizing five breast cancer cell lines derived from primary human breast tumors, we identified BRC-31 as a novel basal-like cell model that expresses elevated FRA-1 levels...
January 30, 2018: Breast Cancer Research: BCR
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