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https://www.readbyqxmd.com/read/29352205/2-5-hexanedione-induces-dopaminergic-neurodegeneration-through-integrin-%C3%AE-m%C3%AE-2-nadph-oxidase-axis-mediated-microglial-activation
#1
Cong Zhang, Liyan Hou, Jie Yang, Yuning Che, Fuqiang Sun, Huihua Li, Qingshan Wang
Recent study demonstrated that chronic exposure to solvents increases the risk of Parkinson's disease (PD), the second most common neurodegenerative disorder characterized by progressive dopaminergic neurodegeneration in the substantia nigra (SN). n-Hexane, a widely used organic solvent, displays central-peripheral neurotoxicity, which is mainly mediated by its active metabolite, 2,5-hexanedione (HD). However, whether HD exposure contributes to PD remains unclear. In this study, we found that rats exposed to HD displayed progressive dopaminergic neurodegeneration in the nigrostriatal system...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351412/expression-of-ctgf-ccn2-in-response-to-lpa-is-stimulated-by-fibrotic-extracellular-matrix-via-the-integrin-fak-axis
#2
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351058/development-and-characterization-of-an-in-vitro-model-for-radiation-induced-fibrosis
#3
Dhruv Kumar, Sreeya Yalamanchali, Jacob New, Sean Parsel, Natalie New, Andrew Holcomb, Sumedha Gunewardena, Ossama Tawfik, Chris Lominska, Bruce F Kimler, Shrikant Anant, Kiran Kakarala, Terance Tsue, Yelizaveta Shnayder, Kevin Sykes, Subhash Padhye, Sufi Mary Thomas
Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β)...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29350833/platelets-kill-bacteria-by-bridging-innate-and-adaptive-immunity-via-pf4-and-fc%C3%AE-riia
#4
R Palankar, T P Kohler, K Krauel, J Wesche, S Hammerschmidt, A Greinacher
BACKGROUND: Activated platelets release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds to polyanions (P) on bacteria, undergoes a conformational change and exposes neoepitopes. These neoepitopes induce production of anti-PF4/P antibodies. As PF4 binds to a variety of bacteria, anti-PF4/P IgG can bind and opsonize several bacterial species. OBJECTIVE: Here we investigated whether platelets are able to kill bacteria directly after recognizing anti-PF4/P IgG opsonized bacteria in the presence of PF4 via their FcγRIIA...
January 19, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29350679/proangiogenic-functions-of-an-rgd-slay-containing-osteopontin-icosamer-peptide-in-huvecs-and-in-the-postischemic-brain
#5
Hahnbie Lee, Yin-Chuan Jin, Seung-Woo Kim, Il-Doo Kim, Hye-Kyung Lee, Ja-Kyeong Lee
Osteopontin (OPN) is a phosphorylated glycoprotein secreted into body fluids by various cell types. OPN contains arginine-glycine-aspartate (RGD) and serine-leucine-alanine-tyrosine (SLAY) motifs that bind to several integrins and mediate a wide range of cellular processes. In the present study, the proangiogenic effects of a 20-amino-acid OPN peptide (OPNpt20) containing RGD and SLAY motifs were examined in human umbilical vein endothelial cells (HUVECs) and in a rat focal cerebral ischemia model. OPNpt20 exerted robust proangiogenic effects in HUVECs by promoting proliferation, migration and tube formation...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350564/role-of-madcam-1-expressing-high-endothelial-venule-like-vessels-in-colitis-induced-in-mice-lacking-sulfotransferases-catalyzing-l-selectin-ligand-biosynthesis
#6
Shulin Low, Jotaro Hirakawa, Hitomi Hoshino, Kenji Uchimura, Hiroto Kawashima, Motohiro Kobayashi
Ulcerative colitis (UC) is a chronic inflammatory disease histologically characterized by diffuse mononuclear cell infiltrates in colonic mucosa. These inflammatory cells are considered to be recruited via high endothelial venule (HEV)-like vessels displaying mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the ligand for α4β7 integrin, and/or peripheral lymph node addressin (PNAd), an L-selectin ligand. 6- O-sulfation of N-acetylglucosamine in the carbohydrate moiety of PNAd is catalyzed exclusively by N-acetylglucosamine-6- O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2...
January 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29349703/matrix-stiffness-the-conductor-of-organ-fibrosis
#7
REVIEW
Alba Santos, David Lagares
PURPOSE OF REVIEW: Organ fibrosis is a lethal component of scleroderma. The hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM) deposition by activated myofibroblasts, specialized hyper-contractile cells that promote ECM remodeling and matrix stiffening. The purpose of this review is to discuss novel mechanistic insight into myofibroblast activation in scleroderma. RECENT FINDINGS: Matrix stiffness, traditionally viewed as an end point of organ fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that hijacks the normal physiologic wound-healing program to promote organ fibrosis...
January 19, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29348803/synthesis-of-a-chloroalkene-dipeptide-isostere-containing-peptidomimetic-and-its-biological-application
#8
Takuya Kobayakawa, Yudai Matsuzaki, Kentaro Hozumi, Wataru Nomura, Motoyoshi Nomizu, Hirokazu Tamamura
The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD) peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained utilizing diastereoselective allylic alkylation as a key reaction. This CADI was also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI-containing cyclic RGD peptide was successful, and the synthesized CADI-containing peptidomimetic was found to be a more potent inhibitor against integrin-mediated cell attachment than the parent cyclic peptide...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#9
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348458/hic-5-regulates-fibrillar-adhesion-formation-to-control-tumor-extracellular-matrix-remodeling-through-interaction-with-tensin1
#10
Gregory J Goreczny, Ian J Forsythe, Christopher E Turner
The linearization of the stromal extracellular matrix (ECM) by cancer-associated fibroblasts (CAFs) facilitates tumor cell growth and metastasis. However, the mechanism by which the ECM is remodeled is not fully understood. Hic-5 (TGFβ1i1), a focal adhesion scaffold protein, has previously been reported to be crucial for stromal ECM deposition and remodeling in vivo. Herein we show that CAFs lacking Hic-5 exhibit a significant reduction in the ability to form fibrillar adhesions, a specialized form of focal adhesion that promote fibronectin fibrillogenesis...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29346935/chase-and-run-dynamics-in-cell-motility-and-the-molecular-rupture-of-interacting-active-elastic-dimers
#11
David Mayett, Nicholas Bitten, Moumita Das, J M Schwarz
Cell migration in morphogenesis and cancer metastasis typically involves interplay between different cell types. We construct and study a minimal, one-dimensional model composed of two different motile cells with each cell represented as an active elastic dimer. The interaction between the two cells via cadherins is modeled as a spring that can rupture beyond a threshold force as it undergoes dynamic loading from the interacting motile cells. We obtain a phase diagram consisting of chase-and-run dynamics and clumping dynamics as a function of the stiffness of the interaction spring and the threshold force and, therefore, posit that active rupture, or rupture via active forces, is a mechanosensitive means to regulate dynamics between cells...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346560/aggregation-and-travelling-wave-dynamics-in-a-two-population-model-of-cancer-cell-growth-and-invasion
#12
Vasiliki Bitsouni, Dumitru Trucu, Mark A J Chaplain, Raluca Eftimie
Cells adhere to each other and to the extracellular matrix (ECM) through protein molecules on the surface of the cells. The breaking and forming of adhesive bonds, a process critical in cancer invasion and metastasis, can be influenced by the mutation of cancer cells. In this paper, we develop a nonlocal mathematical model describing cancer cell invasion and movement as a result of integrin-controlled cell-cell adhesion and cell-matrix adhesion, for two cancer cell populations with different levels of mutation...
January 15, 2018: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#13
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29345322/effect-of-substrate-stiffness-on-hepatocyte-migration-and-cellular-young-s-modulus
#14
Tingting Xia, Runze Zhao, Wanqian Liu, Qiping Huang, Peixing Chen, Yasinta Ningsih Waju, Mohanad Kh Al-Ani, Yonggang Lv, Li Yang
Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver...
January 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29344719/phosphorylation-of-vasodilator-stimulated-phosphoprotein-contributes-to-myocardial-ischemic-preconditioning
#15
David Köhler, Sofia-Iris Bibli, Lothar P Klammer, Judith M Roth, Rainer Lehmann, Ingrid Fleming, Tiago F Granja, Andreas Straub, Peter M Benz, Peter Rosenberger
Ischemic preconditioning (IP) is a well-known strategy to protect organs against cell death following ischemia. The previous work has shown that vasodilator-stimulated phosphoprotein (VASP) is involved in cytoskeletal reorganization and that it holds significant importance for the extent of myocardial ischemia reperfusion injury. Yet, the role of VASP during myocardial IP is, to date, not known. We report here that VASP phosphorylation at serine157 and serine239 is induced during hypoxia in vitro and during IP in vivo...
January 17, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29344222/herbal-compound-teng-long-bu-zhong-tang-inhibits-metastasis-in-human-rko-colon-carcinoma
#16
Meng-Meng Wei, Shuang-Shuang Wang, Jia-Lu Zheng, Jin-Jun Chen, Xia Yan, Hong-Mei An, Bing Hu
Metastasis is one of the primary obstacles to the successful treatment of colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal formula that may be useful in the treatment of metastatic colorectal cancer. The present study evaluated the effects of TLBZT on lung metastasis in human RKO colon carcinoma cells injected into mice via the tail vein. The results demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia-inducible factor 1α...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343555/antagonism-of-integrin-cd11b-affords-protection-against-endotoxin-shock-and-polymicrobial-sepsis-via-attenuation-of-hmgb1-nucleocytoplasmic-translocation-and-extracellular-release
#17
Huiting Zhou, Yanhong Li, Huan Gui, He Zhao, Ming Wu, Gang Li, Yiping Li, Zhenjiang Bai, Zhimin Yin, H Paul Redmond, Jian Wang, Jiang Huai Wang, Zhihui Zhao
High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against LPS- and microbial sepsis-related lethality, which is associated with significantly diminished serum HMGB1 levels...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343182/fibronectin-enhances-cartilage-repair-by-activating-progenitor-cells-through-integrin-%C3%A9-5%C3%AE-1-receptor
#18
Tianqi Tao, Yang Li, Chang Gui, Yong Ma, Yingbin Ge, Hanhao Dai, Kaibin Zhang, Jing Du, Yang Guo, Yiqiu Jiang, Jianchao Gui
This study aimed to determine the effect of fibronectin (FN) on cartilage regeneration through the activation of chondrogenic progenitor cells (CPCs). Cells were isolated from the knee cartilage of mice and cultured in the presence of various concentrations of FN. Proliferation, migration and chondrogenic differentiation assays were performed in vitro. In some experiments, CPCs were pre-incubated with anti-integrin ɑ5β1 antibody for 60 min prior to FN treatment to block the integrin ɑ5β1 receptor. Soluble FN was mixed with Pluronic F-127 and injected into the joint cavity in an early-stage osteoarthritis (OA) model...
January 18, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29342970/the-possible-importance-of-%C3%AE-3-integrins-for-leukemogenesis-and-chemoresistance-in-acute-myeloid-leukemia
#19
REVIEW
Silje Johansen, Annette K Brenner, Sushma Bartaula-Brevik, Håkon Reikvam, Øystein Bruserud
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29341434/recombinant-collagen-scaffolds-as-substrates-for-human-neural-stem-progenitor-cells
#20
Richard A Que, Janahan Arulmoli, Nancy A Da Silva, Lisa A Flanagan, Szu-Wen Wang
Adhesion to the microenvironment profoundly affects stem cell functions, including proliferation and differentiation, and understanding the interaction of stem cells with the microenvironment is important for controlling their behavior. In this study, we investigated the effects of the integrin binding epitopes GFOGER and IKVAV (natively present in collagen I and laminin, respectively) on human neural stem/progenitor cells (hNSPCs). To test the specificity of these epitopes, GFOGER or IKVAV were placed within the context of recombinant triple-helical collagen III engineered to be devoid of native integrin binding sites...
January 17, 2018: Journal of Biomedical Materials Research. Part A
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