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αvβ3 integrin

Haoyu Wang, Renee-Tyler Tan Morales, Xin Cui, Jiongxian Huang, Weiyi Qian, Jie Tong, Weiqiang Chen
Macrophages are a predominant immune cell population that drive inflammatory responses and exhibit transitions in phenotype and function during tissue remodeling in disease and repair. Thus, engineering an immunomodulatory biomaterial has significant implications for resolving inflammation. Here, a biomimetic and photoresponsive hyaluronan (HA) hydrogel nanocomposite with tunable 3D extracellular matrix (ECM) adhesion sites for dynamic macrophage immunomodulation is engineered. Photodegradative alkoxylphenacyl-based polycarbonate (APP) nanocomposites are exploited to permit user-controlled Arg-Gly-Asp (RGD) adhesive peptide release and conjugation to a HA-based ECM for real-time integrin activation of macrophages encapsulated in 3D HA-APP nanocomposite hydrogels...
December 7, 2018: Advanced Healthcare Materials
Seung-Woo Han, Jeong Min Kim, Yunmee Lho, Hyun Jung Cho, Youn-Kwan Jung, Jung-Ae Kim, Hoyul Lee, Yu-Jeong Lee, Eun Soo Kim
Background: Adhesion molecules maintain the intestinal barrier function that is crucial to prevent intestinal inflammation. Dual immunoglobulin domain-containing adhesion molecule (DICAM) has been recently identified and known for the involvement in cell-cell adhesion through homophilic interaction and heterophilic interaction with integrin αVβ3. We tested whether the change of DICAM expression affects the severity of colonic inflammation. Methods: Colitis was induced with oral administration of 2...
December 9, 2018: Inflammatory Bowel Diseases
Takafumi Kawamura, Masayoshi Yamamoto, Katsunori Suzuki, Yuhi Suzuki, Megumu Kamishima, Mayu Sakata, Kiyotaka Kurachi, Mitsutoshi Setoh, Hiroyuki Konno, Hiroya Takeuchi
Background: Colitis-associated cancer (CAC) is one of the prognostic factors in inflammatory bowel disease (IBD), and prevention of CAC is a critical concern for patients with IBD. Component cells of the microenvironment, especially myofibroblasts, are known to affect tumor development, but the role of intestinal myofibroblasts (IMFs) in CAC has not been clarified. Here, we explored the role of IMFs in CAC and sought to identify candidate genes as novel therapeutic targets for the prevention of CAC...
December 4, 2018: Inflammatory Bowel Diseases
Saeed Balalaie, Fatima Hamdan, Zahra Bigdeli, S Mohsen Asghari, Afsaneh Sadremomtaz
RGD peptides represent the most outstanding recognition motif involved in cell adhesion and binds to αvβ3 integrin that has been targeted for cancer therapy. Various RGD-containing peptides and peptidomimetics have been designed and synthesized to selectively inhibit this integrin.In this study, the synthesis of RGD based peptides through the incorporation of the short bioactive peptide FAKLF at the C- and N- terminus of RGD has been achieved using solid phase peptide synthesis approach. The peptides were purified using preparative RP-HPLC and their structures were confirmed using HR-MS (ESI)...
December 1, 2018: ChemMedChem
Yin Song, Wei Li, Shuyan Meng, Wei Zhou, Bo Su, Liang Tang, Yinmin Zhao, Xiaoyan Wu, Dazhi Yin, Mingxia Fan, Caicun Zhou
Enhanced MRI (magnetic resonance imaging) plays a vital role in the early detection of tumor but with low specificity. Molecular imaging of angiogenesis could efficiently deliver contrast agents to the tumor site by specific targeted carriers. We designed and synthesized dual-targeted paramagnetic liposomes functionalized with two angiogenesis-targeting ligands, the αVβ3 integrin-specific RGD (Arg-Gly-Asp) and the neuropilin-1 (NRP-1) receptor-specific ATWLPPR (Ala-Thr-Trp-Leu-Pro-Pro-Arg) (A7R). These liposomes were proved to be in the nanoparticle range and demonstrated to effectively encapsulate paramagnetic MRI contrast agents Gd-DTPA (gadolinium-diethylenetriamine pentaacetic acid)...
November 27, 2018: Nanoscale Research Letters
Inna Szekacs, Eniko Farkas, Borbala Leticia Gemes, Eszter Takacs, Andras Szekacs, Robert Horvath
This study is a discovery of interesting and far reaching properties of the world leading herbicide active ingredient glyphosate. Here we demonstrate the cell adhesion-modifying characteristics of glyphosate affecting cellular interactions via Arg-Gly-Asp (RGD)-dependent integrins. This conclusion was supported by the observations that a glyphosate surface coating induced integrin-specific cell adhesion, while glyphosate in solution inhibited cell adhesion on an RGD-displaying surface. A sensitive, real-time, label-free, whole cell approach was used to monitor the cell adhesion kinetic processes with excellent data quality...
November 27, 2018: Scientific Reports
Hua-Ying Cai, Ke-Wei Tian, Yuan-Yuan Zhang, Hong Jiang, Shu Han
Amyotrophic lateral sclerosis (ALS) is an adult disorder of neurodegeneration that manifests as the destruction of upper and lower motor neurons. Beta-N-methylamino-L-alanine (L-BMAA), an amino acid not present in proteins, was found to cause intraneuronal protein misfolding and to induce ALS/Parkinsonism dementia complex (PDC), which presents symptoms analogous to those of Alzheimer's-like dementia and Parkinsonism. L-serine suppresses the erroneous incorporation of L-BMAA into proteins in the human nervous system...
November 25, 2018: Aging
Zhiguo Sheng, Cong Wang, Furong Ren, Yuxiang Liu, Benzhan Zhu
Bisphenol A (BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins. Inevitably, general population has been widely exposed to BPA due to extensive use of BPA-containing products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors (ERs) by directly regulating the genomic transcription...
January 2019: Journal of Environmental Sciences (China)
André Raposo Moreira Dias, Arianna Pina, Amelia Dean, Hans-Georg Lerchen, Michele Caruso, Fabio Gasparri, Ivan Fraietta, Sonia Troiani, Daniela Arosio, Laura Belvisi, Luca Pignataro, Alberto Dal Corso, Cesare Gennari
We took advantage of one of the hallmarks of cancers, i.e. the presence of tumor infiltrating cells of the immune system and leukocyte-secreted enzymes, to promote the activation of an anticancer drug at the tumor site. The peptidomimetic integrin ligand cyclo(DKP-RGD) was found to accumulate on the surface of αvβ3 integrin-expressing human renal cell carcinoma 786-O cells. The ligand was conjugated to the anticancer drug paclitaxel through a Asn-Pro-Val (NPV) tripeptide linker, which is a substrate of neutrophil-secreted elastase...
November 19, 2018: Chemistry: a European Journal
Janine Schniering, Martina Benešová, Matthias Brunner, Stephanie Haller, Susan Cohrs, Thomas Frauenfelder, Bart Vrugt, Carol A Feghali-Bostwick, Roger Schibli, Oliver Distler, Cristina Mueller, Britta Maurer
OBJECTIVE: To evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD). METHODS: The pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting 177 Lu-DOTA-RGD and the SSTR2-targeting 177 Lu-DOTA-NOC radiotracer...
November 17, 2018: Annals of the Rheumatic Diseases
Massimo Dal Monte, Maurizio Cammalleri, Valeria Pecci, Monica Carmosino, Giuseppe Procino, Alessandro Pini, Mario De Rosa, Vincenzo Pavone, Maria Svelto, Paola Bagnoli
The urokinase-type plasminogen activator (uPA) receptor (uPAR) participates to the mechanisms causing renal damage in response to hyperglycaemia. The main function of uPAR in podocytes (as well as soluble uPAR -(s)uPAR- from circulation) is to regulate podocyte function through αvβ3 integrin/Rac-1. We addressed the question of whether blocking the uPAR pathway with the small peptide UPARANT, which inhibits uPAR binding to the formyl peptide receptors (FPRs) can improve kidney lesions in a rat model of streptozotocin (STZ)-induced diabetes...
November 13, 2018: Journal of Cellular and Molecular Medicine
Zheyu Shen, Ting Liu, Yan Li, Joseph Lau, Zhen Yang, Wenpei Fan, Zijian Zhou, Changrong Shi, Chaomin Ke, Vladimir I Bregadze, Swadhin K Mandal, Yijing Liu, Zihou Li, Ting Xue, Guizhi Zhu, Jeeva Munasinghe, Gang Niu, Aiguo Wu, Xiaoyuan Chen
Cancer is one of the leading causes of morbidity and mortality in the world, but more cancer therapies are needed to complement existing regimens due to problems of existing cancer therapies. Herein, we term ferroptosis therapy (FT) as a form of cancer therapy and hypothesize that the FT efficacy can be significantly improved via accelerating the Fenton reaction by simultaneously increasing the local concentrations of all reactants (Fe2+ , Fe3+ , and H2 O2 ) in cancer cells. Thus, Fenton-reaction-acceleratable magnetic nanoparticles, i...
November 27, 2018: ACS Nano
Stefanie R Guenther, Ricarda G Schumann, Felix Hagenau, Armin Wolf, Siegfried G Priglinger, Denise Vogt
PURPOSE: To describe and compare characteristics of premacular membranes in idiopathic macular pucker (iMP) and proliferative vitreoretinopathy (PVR) using immunofluorescence and transmission electron microscopy. MATERIALS AND METHODS: For immunocytochemical and ultrastructural analyses, premacular membranes were harvested during vitrectomy from 16 eyes with iMP and 12 eyes with PVR. All specimens were processed as flat mounts for phase-contrast and fluorescence microscopy...
October 29, 2018: Current Eye Research
Junyu Cao, Jie Li, Liankang Sun, Tao Qin, Ying Xiao, Ke Chen, Weikun Qian, Wanxing Duan, Jianjun Lei, Jiguang Ma, Qingyong Ma, Liang Han
Pancreatic stellate cells (PSCs), a key component of the tumor microenvironment, contribute to tumor invasion, metastasis, and chemoresistance. Osteopontin (OPN), a phosphorylated glycoprotein, is overexpressed in pancreatic cancer. However, OPN expression in PSCs and its potential roles in tumor-stroma interactions remain unclear. The present study first showed that OPN is highly expressed and secreted in activated PSCs driven by hypoxia, and this process is in a ROS-dependent manner; in addition, OPN was shown to be involved in the PSC-induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of pancreatic cancer cells (PCCs)...
October 27, 2018: Molecular Oncology
Arantxa Blázquez-Prunera, Catarina R Almeida, Mario A Barbosa
Human mesenchymal stem cells (MSC) are being explored for cell therapies targeting varied human diseases. For that, cells are being expanded in vitro, many times with fetal bovine serum (FBS) as the main source of growth factors. However, animal-derived components should not be used, to avoid immune rejection from the patient that receives the MSC. To solve this issue, different xeno-free media are being developed and an industrial-grade human plasma fraction (SCC) is a promising candidate to substitute FBS...
October 26, 2018: Journal of Tissue Engineering and Regenerative Medicine
Manuela Moriggi, Marta Giussani, Enrica Torretta, Daniele Capitanio, Marco Sandri, Roberta Leone, Sara De Palma, Michele Vasso, Giovanni Vozzi, Elda Tagliabue, Cecilia Gelfi
Tumor extracellular matrix (ECM) plays a pivotal role in outcome of breast cancer (BC) patients. Overespression of 58 genes, encoding 43 structural ECM proteins, has been identified to determine a specific cluster of BC with accelerated metastatic potential only in the undifferentiated (grade III) phenotype. The scope of this study was to characterize protein repertoire able to predict patient outcome in BC according to ECM gene expression pattern and histological grade. The differential proteomic analysis has been based on 2D-DIGE, MALDI-MS, bioinformatics and immunoblotting...
October 24, 2018: Proteomics
Hung-Yun Lin, Yu-Tang Chin, Ya-Jung Shih, Yi-Ru Chen, Matthew Leinung, Kelly A Keating, Shaker A Mousa, Paul J Davis
The PD-1/PD-L1 immune checkpoint involving tumor cells and host immune defense lymphocytes is a well-studied therapeutic target in oncology. That PD-1 and PD-L1 may have additional functions within tumor cells that are independent of the checkpoint is indicated by actions of a thyroid hormone analogue, L-thyroxine (T4 ), on these checkpoint components. Acting at a cell surface receptor on plasma membrane integrin αvβ3, T4 stimulates intracellular accumulation of PD-L1 in cancer cells. In these thyroid hormone-treated cells, T4 -induced PD-L1 is non-immunologically anti-apoptotic, blocking activation of p53...
September 25, 2018: Oncotarget
Vincent F Fiore, Simon S Wong, Coleen Tran, Chunting Tan, Wenwei Xu, Todd Sulchek, Eric S White, James S Hagood, Thomas H Barker
Fibrosis is characterized by persistent deposition of extracellular matrix (ECM) by fibroblasts. Fibroblast mechanosensing of a stiffened ECM is hypothesized to drive the fibrotic program; however, the spatial distribution of ECM mechanics and their derangements in progressive fibrosis are poorly characterized. Importantly, fibrosis presents with significant histopathological heterogeneity at the microscale. Here, we report that fibroblastic foci (FF), the regions of active fibrogenesis in idiopathic pulmonary fibrosis (IPF), are surprisingly of similar modulus as normal lung parenchyma and are nonlinearly elastic...
October 18, 2018: JCI Insight
Davor Nestić, Taco G Uil, Jiangtao Ma, Soumitra Roy, Jort Vellinga, Andrew H Baker, Jerome Custers, Dragomira Majhen
Human adenoviruses (HAdVs) are being explored as vectors for gene transfer and vaccination. Human adenovirus type 26 (HAdV26), which belongs to the largest subgroup of adenoviruses, species D, has a short fiber and a so far unknown natural tropism. Due to its low seroprevalence, HAdV26 has been considered a promising vector for the development of vaccines. Despite the fact that the in vivo safety and immunogenicity of HAdV26 has been extensively studied, the basic biology of this virus, with regard to receptor use, cell attachment, internalization and intracellular trafficking is poorly understood...
October 17, 2018: Journal of Virology
Yanping Lu, Shunping Han, Hongyue Zheng, Rui Ma, Yuting Ping, Jiafeng Zou, Hongxia Tang, Yongping Zhang, Xiuling Xu, Fanzhu Li
Background: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2 O3 ) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. Purpose: The objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment...
2018: International Journal of Nanomedicine
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