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https://www.readbyqxmd.com/read/28535041/remarkably-stereospecific-utilization-of-atp-%C3%AE-%C3%AE-halomethylene-analogues-by-protein-kinases
#1
Feng Ni, Alvin Kung, Yankun Duan, Vivek Shah, Carolina Amador, Ming Guo, Xuegong Fan, Lin Chen, Yongheng Chen, Charles E McKenna, Chao Zhang
ATP analogues containing a CXY group in place of the α,β-bridging oxygen atom are powerful chemical probes for studying ATP-dependent enzymes. A limitation of such probes has been that conventional synthetic methods generate a mixture of diastereomers when the bridging carbon substitution is nonequivalent (X ≠ Y). We report here a novel method based on derivatization of a bisphosphonate precursor with a D-phenylglycine chiral auxiliary that enables preparation of the individual diastereomers of α,β-CHF-ATP and α,β-CHCl-ATP, which differ only in the configuration at the CHX carbon...
May 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28534941/two-natural-eudesmane-type-sesquiterpenes-from-laggera-alata-inhibit-angiogenesis-and-suppress-breast-cancer-cell-migration-through-vegf-and-angiopoietin-2-mediated-signaling-pathways
#2
Ning Liang, Yaolan Li, Hau Yin Chung
Eudesmane-type sesquiterpenes are natural sesquiterpenes with anti-inflammatory properties, but their anti-angiogenic activities are not known. The present study demonstrated that 5α-hydroxycostic acid and hydroxyisocostic acid, two eudesmane-type sesquiterpenes (ETSs), isolated from the herb Laggera alata, possessed anti-angiogenic effects. Under non-toxic dosage, ETSs suppressed VEGF‑induced proliferation in human umbilical vein endothelial cells (HUVECs) and vessel formation in zebrafish embryos. Moreover, ETSs inhibited VEGF-stimulated HUVEC migration, stress fibers and tube formation...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#3
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28529128/role-of-gper-in-the-activation-of-endothelial-nitric-oxide-synthase
#4
Natalie C Fredette, Matthias R Meyer, Eric R Prossnitz
Estrogens are potent regulators of vascular tone, yet underlying receptor- and ligand-specific signaling pathways remain poorly characterized. The primary physiological estrogen 17β-estradiol (E2), a non-selective agonist of classical nuclear estrogen receptors (ERα and ERβ) as well as the G protein-coupled estrogen receptor (GPER), stimulates formation of the vasodilator nitric oxide (NO) in endothelial cells. Here, we studied the contribution of GPER signaling in E2-dependent activation of endothelial NO formation and subsequent vasodilation...
May 18, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28529061/benzo-a-pyrene-7-8-diol-9-10-epoxide-suppresses-the-migration-and-invasion-of-human-extravillous-trophoblast-htr-8-svneo-cells-by-down-regulating-mmp2-through-inhibition-of-fak-src-pi3k-akt-pathway
#5
Rong Wang, Weiping Wang, Lin Ao, Zhi Wang, Xianglin Hao, Huidong Zhang
Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0μM BPDE for 24h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0...
May 18, 2017: Toxicology
https://www.readbyqxmd.com/read/28528309/maintenance-of-claudin-3-expression-and-the-barrier-functions-of-intercellular-junctions-in-parotid-acinar-cells-via-the-inhibition-of-src-signaling
#6
Megumi Yokoyama, Takanori Narita, Hajime Sakurai, Osamu Katsumata-Kato, Hiroshi Sugiya, Junko Fujita-Yoshigaki
OBJECTIVES: Salivary acinar and duct cells show different expression patterns of claudins, which may reflect their different functions. To study the role of claudins in saliva secretion, we examined alterations in the expression patterns of cell adhesion molecules in parotid glands of γ-irradiated rats and analyzed the influence of those changes on intercellular barrier function using primary cultures of parotid acinar cells. DESIGN: Rats were γ-irradiated with doses of 5, 15 or 20Gy, and expression levels of cell adhesion molecules were examined by immunoblotting analysis...
May 15, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28527916/cadmium-stimulates-metastasis-associated-phenotype-in-triple-negative-breast-cancer-cells-through-integrin-and-%C3%AE-catenin-signaling
#7
Zhengxi Wei, Zahir A Shaikh
Cadmium (Cd) is a carcinogenic heavy metal which is implicated in breast cancer development. While the mechanisms of Cd-induced breast cancer initiation and promotion have been studied, the molecular processes involved in breast cancer progression remain to be investigated. The purpose of the present study was to evaluate the influence of Cd on metastasis-associated phenotypes, such as cell adhesion, migration, and invasion in triple-negative breast cancer cells. Treatment of MDA-MB-231 cells with 1μM Cd increased cell spreading and cell migration...
May 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28525838/design-synthesis-and-evaluation-of-azaacridine-derivatives-as-dual-target-egfr-and-src-kinase-inhibitors-for-antitumor-treatment
#8
Zhishan Cui, Shaopeng Chen, Yanwei Wang, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Overexpression of EGFR is often associated with advanced stage disease and poor prognosis. In certain cancers, Src works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and Src is of therapeutic advantage against these cancers. Based on molecular docking and our previous studies, we rationally designed a new series of azaacridine derivatives as potent EGFR and Src dual inhibitors. Most of the synthesized azaacridines displayed good antiproliferative activity against K562 and A549 cells...
May 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28522963/the-f-actin-binding-protein-cortactin-regulates-the-dynamics-of-the-exocytotic-fusion-pore-through-its-sh3-domain
#9
Arlek M González-Jamett, María J Guerra, María J Olivares, Valentina Haro-Acuña, Ximena Baéz-Matus, Jacqueline Vásquez-Navarrete, Fanny Momboisse, Narcisa Martinez-Quiles, Ana M Cárdenas
Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca(2+) signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#10
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522592/sensitization-of-egfr-wild-type-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitor-erlotinib
#11
Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, Ludmilla de Plater, Fanny Bouquet, Ariel Savina, Didier Decaudin, Jaafar Bennouna, François M Vallette, Lisenn Lalier
The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522571/flt3-and-flt3-itd-phosphorylate-and-inactivate-the-cyclin-dependent-kinase-inhibitor-p27kip1-in-acute-myeloid-leukemia
#12
Ines Peschel, Silvio R Podmirseg, Martin Taschler, Justus Duyster, Katharina S Götze, Heinz Sill, David Nachbaur, Heidelinde Jäkel, Ludger Hengst
p27Kip1 can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. We observed that FLT3 and FLT3-ITD can directly bind and selectively phosphorylate p27 on this residue. Inhibition of FLT3-ITD in cell lines strongly reduced p27 tyrosine 88 phosphorylation and resulted in increased p27 levels and cell cycle arrest. Subsequent analysis revealed the presence of tyrosine 88 phosphorylated p27 in primary patient samples...
May 18, 2017: Haematologica
https://www.readbyqxmd.com/read/28522221/comparative-efficacy-and-safety-of-different-circumcisions-for-patients-with-redundant-prepuce-or-phimosis-a-network-meta-analysis
#13
REVIEW
Chuiguo Huang, Pan Song, Changbao Xu, Ruofan Wang, Lei Wei, Xinghua Zhao
BACKGROUND: Phimosis and redundant prepuce are defined as the inability of the foreskin to be retracted behind the glans penis in uncircumcised males. To synthesize the evidence and provide the hierarchies of different circumcisions for phimosis and redundant prepuce, we performed an overall network meta-analysis (NMA) based on their comparative efficacy and safety. MATERIAL AND METHODS: Electronic databases including PubMed, Embase, Wan Fang, VIP, CNKI and CBM database were researched from randomized controlled trials (RCTs) for redundant prepuce or phimosis...
May 15, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28520882/ocular-determinants-of-refractive-error-and-its-age-and-sex-related-variations-in-the-chinese-american-eye-study
#14
Grace M Richter, Mingwu Wang, Xuejuan Jiang, Shuang Wu, Dandan Wang, Mina Torres, Farzana Choudhury, Rohit Varma
Importance: Uncorrected refractive error (RE) is a leading cause of visual impairment, and variations in ocular anatomy determine RE. The unique ocular determinants of RE in Chinese American individuals have not been studied previously. Objective: To report ocular determinants of RE in a Chinese American population 50 years and older in Monterey Park, California. Design, Setting, and Participants: The Chinese American Eye Study, a population-based, cross-sectional study, was conducted from February 1, 2010, through October 31, 2013, in Monterey Park, with this particular data analysis performed from January 1 through December 31, 2016...
May 18, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28520795/birc6-mediates-imatinib-resistance-independently-of-mcl-1
#15
Denis O Okumu, Michael P East, Merlin Levine, Laura E Herring, Raymond Zhang, Thomas S K Gilbert, David W Litchfield, Yanping Zhang, Lee M Graves
Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL)...
2017: PloS One
https://www.readbyqxmd.com/read/28516374/role-of-lps-elicited-signaling-in-triggering-gastric-mucosal-inflammatory-responses-to-h-pylori-modulatory-effect-of-ghrelin
#16
REVIEW
B L Slomiany, A Slomiany
Infection with Helicobacter pylori is a primary culprit in the etiology of gastric disease, and its cell-wall lipopolysaccharide (LPS) is recognized as a potent endotoxin responsible for triggering a pattern of the mucosal inflammatory responses. The engagement by the LPS of gastric mucosal Toll-like receptor 4 (TLR4) leads to initiation of signal transduction events characterized by the activation of mitogen-activated protein kinase (MAPK) cascade, induction of phosphoinositide-specific phospholipase C (PLC)/protein kinase C (PKC)/phosphatidylinositol 3-kinase (PI3K) pathway, and up-regulation in Src/Akt...
May 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28514658/cns-macrophages-control-neurovascular-development-via-cd95l
#17
Si Chen, Nathalie Tisch, Marcel Kegel, Rosario Yerbes, Robert Hermann, Hannes Hudalla, Cecilia Zuliani, Gülce Sila Gülcüler, Klara Zwadlo, Jakob von Engelhardt, Carmen Ruiz de Almodóvar, Ana Martin-Villalba
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28512713/matairesinol-suppresses-neuroinflammation-and-migration-associated-with-src-and-erk1-2-nf-%C3%AE%C2%BAb-pathway-in-activating-bv2-microglia
#18
Peng Xu, Meng-Wei Huang, Chen-Xi Xiao, Fen Long, Ying Wang, Si-Yu Liu, Wan-Wan Jia, Wei-Jun Wu, Di Yang, Jin-Feng Hu, Xin-Hua Liu, Yi-Zhun Zhu
Chronic neuroinflammation is a pathological feature of neurodegenerative diseases. Inhibition of microglia-mediated neuroinflammation might be a potential strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant lignan, presents in a wide variety of foodstuffs. It has been found to possess anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the present study, we investigated the anti-neuroinflammation effects of matairesinol on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular mechanisms...
May 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28512645/regulation-of-discrete-functional-responses-by-syk-and-src-family-tyrosine-kinases-in-human-neutrophils
#19
Thornin Ear, Olga Tatsiy, Frédérick L Allard, Patrick P McDonald
Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28512623/ca-2-microdomains-in-t-lymphocytes
#20
REVIEW
Insa M A Wolf, Andreas H Guse
Early Ca(2+) signaling is characterized by occurrence of Ca(2+) microdomains formed by opening of single or clusters of Ca(2+) channels, thereby initiating first signaling and subsequently activating global Ca(2+) signaling mechanisms. However, only few data are available focusing on the first seconds and minutes of Ca(2+) microdomain formation and related signaling pathways in activated T-lymphocytes. In this review, we condense current knowledge on Ca(2+) microdomain formation in T-lymphocytes and early Ca(2+) signaling, function of Ca(2+) microdomains, and microdomain organization...
2017: Frontiers in Oncology
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