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Jeong In Kim, Cheol Sang Kim
The cells respond to their microenvironment which is comparable size to the cells. The macroscale features of three dimensional (3D) printing struts (PS) typically result in whole cell contact guidance (CCG). In contrast, at the nanoscale, where features are similar size to receptors of the cells, the response of cells is more complex. In detail, integrin that is one of the cellular receptors involved with cell adhesion is recognized as communication channels through that the cells interact with adjacent surface features...
March 21, 2018: ACS Applied Materials & Interfaces
Fang-Yu Liu, Te-Cheng Hsu, Patrick Choong, Min-Hsuan Lin, Yung-Jen Chuang, Bor-Sen Chen, Che Lin
BACKGROUND: Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike's Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina...
March 19, 2018: BMC Systems Biology
Takuro Kobori, Shinichi Hamasaki, Atsuhiro Kitaura, Yui Yamazaki, Takashi Nishinaka, Atsuko Niwa, Shinichi Nakao, Hidenori Wake, Shuji Mori, Tadashi Yoshino, Masahiro Nishibori, Hideo Takahashi
M2 macrophage (Mφ) promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell-cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL)-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 Mφs in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse Mφ-like cell line, RAW264...
2018: Frontiers in Immunology
Yunus E Demiray, Kati Rehberg, Stefanie Kliche, Oliver Stork
The serine/threonine kinase Ndr2 has been shown to control the inside-out activation of the β1 subunit of integrins and the formation of neurites in both primary neurons and neurally differentiated pheochromacytoma (PC12) cells. In this study, we demonstrate that Ndr2 kinase furthermore determines the substrate specificity of neurite extension in PC12 cells via expression of α1 β1 integrins. We show that stable overexpression of Ndr2 in PC12 cells increases neurite growth and extension on poly-D-lysine substrate, likely involving an increased expression of active β1 integrin in the growth tips of these cells...
2018: Frontiers in Molecular Neuroscience
Biao Zeng, Min Zhou, Huan Wu, Zhengai Xiong
Objectives: Ovarian cancer is one of the most lethal malignant tumors in women. Secreted phosphoprotein 1 (SPP1) plays an important role in some cancer types. Therefore, the role of SPP1 in ovarian cancer was determined and the potential mechanism was elucidated. Materials and methods: The expression of SPP1 in ovarian cancer was determined by immunohistochemistry in ovarian cancer tissues and normal ovarian tissues. Cellular proliferation, migration, and invasion were determined by cell counting kit-8 assay, wound healing assay, and Matrigel invasion assay in SKOV3 and A2780 cells...
2018: OncoTargets and Therapy
Kristina Busygina, Janina Jamasbi, Till Seiler, Hans Deckmyn, Christian Weber, Richard Brandl, Reinhard Lorenz, Wolfgang Siess
Interaction of Von Willebrand factor (VWF) with platelet glycoprotein (GP) Ib and of collagen with GPVI is essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk) which can irreversibly be blocked by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long term safety. We found that ibrutinib and the novel Btk-inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid...
March 20, 2018: Blood
Xinhua Yu, Reza Akbarzadeh, Mario Pieper, Thomas Scholzen, Stefanie Gehrig, Carsten Schultz, Detlef Zillikens, Peter König, Frank Petersen
Although uncontrolled proteolytic activity mediated by activated neutrophils is a major reason for tissue damage, therapeutic approaches using protease inhibitors are inefficient. Here, we investigated the role of the immune complex-induced neutrophil adhesion and protease release in tissue damage. We show both in vitro and in vivo that immune complex-mediated neutrophil adhesion to the target tissue depends on β2 integrins. Without affecting elastase or ROS release, blocking of adhesion drastically inhibited tissue damage in an experimental model of autoantibody-mediated skin blistering disease...
March 17, 2018: Journal of Investigative Dermatology
Erhao Zhang, Jieyi Gu, Jianpeng Xue, Chenyu Lin, Chen Liu, Mengwei Li, Jingchao Hao, Sarra Setrerrahmane, Xiaowei Chi, Weiyan Qi, Jialiang Hu, Hanmei Xu
BACKGROUND: Chimeric antigen receptors (CARs) presented on T cell surfaces enable redirection of T cell specificity, which has enormous promise in antitumor therapy. However, excessive activity and poor control over such engineered T cells cause significant safety challenges, such as cytokine release syndrome and organ toxicities. To enhance the specificity and controllable activity of CAR-T cells, we report a novel switchable dual-receptor CAR-engineered T (sdCAR-T) cell and a new switch molecule of FITC-HM-3 bifunctional molecule (FHBM) in this study...
March 20, 2018: Journal of Hematology & Oncology
Celina Yang, Kyle Bromma, Devika Chithrani
Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo models. A diameter of 10 nm sized GNP was selected for this study for sufficient penetration through tumor tissue...
March 20, 2018: Cancers
M Di Giulio, V Di Valerio, D Bosco, E Marsich, A Cataldi, L Cellini, S Sancilio
The molecular mechanisms leading to Streptococcus mitis capability of entering oral cells were investigated in a co-culture of S. mitis and Human Gingival Fibroblasts (HGFs) in the presence of saliva. An innovative colloidal solution based on silver nanoparticles (Chitlac-nAg), a promising device for daily oral care, was added to the experimental system in order to study the effects of silver on the bacterial overgrowth and ability to enter non-phagocytic eukaryotic cells. The entry of bacteria into the eukaryotic cells is mediated by a signalling pathway involving FAK, integrin β1, and the two cytoskeleton proteins vinculin and F-actin, and down-regulated by the presence of saliva both at 3 and 48 h of culture, whereas Chitlac-n Ag exposure seems to influence, by incrementing it, the number of bacteria entering the fibroblasts only at 48 h...
March 19, 2018: Journal of Materials Science. Materials in Medicine
Bram Verstockt, Marc Ferrante, Séverine Vermeire, Gert Van Assche
The advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD in the last 15 years, but primarily and more importantly secondary loss of response is often observed. Fortunately , new treatment options have been actively explored and some have already entered our clinical practice. In the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have entered clinical practice with the anti-p40 mAb ustekinumab in Crohn's disease (CD). Also, more selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream which have failed in clinical trials despite their clear efficacy in psoriasis (Verstockt et al...
March 19, 2018: Journal of Gastroenterology
Boju Pan, Junchao Guo, Quan Liao, Yupei Zhao
Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical...
April 2018: Oncology Letters
Yu-Tang Chin, Po-Li Wei, Yih Ho, André Wendindondé Nana, Chun A Changou, Yi-Ru Chen, Yu-Chen Sh Yang, Meng-Ti Hsieh, Aleck Hercbergs, Paul J Davis, Ya-Jung Shih, Hung-Yun Lin
Thyroid hormone as L-thyroxine (T4 ), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2...
March 19, 2018: Endocrine-related Cancer
Yonglin Yu, Xinkun Shen, Zhong Luo, Yan Hu, Menghuan Li, Pingping Ma, Qichun Ran, Liangliang Dai, Ye He, Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc.) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro. Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment, small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation...
March 13, 2018: Biomaterials
K Imakawa, R Bai, K Kusama
During the peri-implantation period, ruminant conceptuses go through rapid elongation, followed by their attachment to the uterine endometrial epithelial cells, during which interferon-tau (IFNT), a trophectodermal cytokine required for the process of maternal recognition of pregnancy, is expressed in a temporal and spatial manner. On d 22 (d 0 = day of estrus), 2 to 3 d after the initiation of bovine conceptus attachment to the uterine epithelium, when IFNT production begins to subside, the expression of molecules related to epithelial-mesenchymal transition, zinc finger E-box binding homeobox 1, snail family transcriptional repressor 2, N-cadherin and vimentin was found in the trophectoderm...
March 15, 2018: Journal of Animal Science
Johannes A Eble
The dissociation constant describes the interaction between two partners in the binding equilibrium and is a measure of their affinity. It is a crucial parameter to compare different ligands, e.g., competitive inhibitors, protein isoforms and mutants, for their binding strength to a binding partner. Dissociation constants are determined by plotting concentrations of bound versus free ligand as binding curves. In contrast, titration curves, in which a signal that is proportional to the concentration of bound ligand is plotted against the total concentration of added ligand, are much easier to record...
February 15, 2018: Journal of Visualized Experiments: JoVE
Michelle E Maxson, Xenia Naj, Teresa R O'Meara, Jonathan D Plumb, Leah E Cowen, Sergio Grinstein
Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane...
March 19, 2018: ELife
Victor O Oria, Paul Lopatta, Oliver Schilling
A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, proliferation, and cell-cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation...
March 17, 2018: Cellular and Molecular Life Sciences: CMLS
Yukiko Kariya, Midori Oyama, Yasuhiro Hashimoto, Jianguo Gu, Yoshinobu Kariya
Malignant transformation is associated with aberrant N-glycosylation, but the role of protein N-glycosylation in cancer progression remains poorly defined. β4-integrin is a major carrier of N-glycans and is associated with poor prognosis, tumorigenesis, and metastasis. Here, N-glycosylation of β4-integrin contributes to the activation of signaling pathways that promote β4-dependent tumor development and progression. Increased expression of β1,6GlcNAc-branched N-glycans was found to be co-localized with β4-integrin in human cutaneous squamous cell carcinoma tissues, and that the β1,6GlcNAc residue was abundant on β4-integrin in transformed keratinocytes...
March 16, 2018: Molecular Cancer Research: MCR
Anton G Kutikhin, Maxim Yu Sinitsky, Arseniy E Yuzhalin, Elena A Velikanova
The blood flow through vessels produces a tangential, or shear, stress sensed by their innermost layer (i.e., endothelium) and representing a major hemodynamic force. In humans, endothelial repair and blood vessel formation are mainly performed by circulating endothelial progenitor cells (EPCs) characterized by a considerable expression of vascular endothelial growth factor receptor 2 (VEGFR2), CD34, and CD133, pronounced tube formation activity in vitro, and strong reendothelialization or neovascularization capacity in vivo...
March 13, 2018: Journal of Molecular and Cellular Cardiology
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