المؤلفون: Zheng Ping, Abha Soni, Lance A. Williams III, Huy P. Pham, Malay K. Basu, X. Long Zheng

المصدر: TH Open, Vol 01, Iss 02, Pp e113-e121 (2017)

مصطلحات موضوعية: coagulation factors, tumor metastasis, factor viii, von willebrand factor, adams/adamts13, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Coagulation factor VIII (FVIII), von Willebrand factor (VWF), and ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats 13) play an important role in the regulation of normal hemostasis. However, little is known about their roles in patients with malignancy, particularly with cutaneous melanoma. Whole genome sequencing data are available for 25,719 cases in 126 cancer genomic studies for analysis. All sequencing data and corresponding pathology findings were obtained from The Cancer Genome Atlas. The cBioPortal bioinformatics tools were used for the data analysis. Our results demonstrated that mutations in genes encoding FVIII, VWF, and ADAMTS13 were reported in 92 of 126 cancer genomic studies, and high mutation rates in these three genes were observed in patients with cutaneous melanoma from three independent studies. Moreover, high mutation rates in FVIII, VWF, and ADAMTS13 were also found in patients with diffuse large B cell lymphoma (22.9%), lung small cell carcinoma (20.7%), and colon adenocarcinoma (19.4%). Among 366 melanoma cases from TCGA provisional, the somatic mutation rates of FVIII, VWF, and ADAMTS13 in tumor cells were 15, 14, and 5%, respectively. There was a strong tendency for coexisting mutations of FVIII, VWF, and ADAMTS13. Kaplan–Meier survival analysis demonstrated that melanoma patients with FVIII mutations had a more favorable overall survival rate than those without FVIII mutations (p = 0.02). These findings suggest, for the first time, that the FVIII mutation burden may have a prognostic value for patients with cutaneous melanoma. Further studies are warranted to delineate the molecular mechanisms underlying the favorable prognosis associated with FVIII mutations.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2512-9465Test

الوصول الحر: https://doaj.org/article/4ced5dd87dea4668b415e789460a589cTest

المؤلفون: Qiang Chen, Karlheinz Peter, Zhou Zhou, Song Peng, Jun Jie Bei, Xiao Long Qu, Zheng Ping Yu, Hou Yuan Hu, Chuan Liu, Cheng Hai Liu, Wei Bo Zhao

المصدر: Thrombosis and Haemostasis. 115:632-645

مصطلحات موضوعية: Blood Platelets, 0301 basic medicine, Staphylococcus aureus, Interleukin-1beta, Active Transport, Cell Nucleus, Inflammation, 030204 cardiovascular system & hematology, Monocytes, Receptors, Tumor Necrosis Factor, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Cell Movement, Cell-Derived Microparticles, Humans, Medicine, Platelet, Gene Silencing, Platelet activation, CD40 Antigens, RNA, Small Interfering, Chemokine CCL2, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha, business.industry, Activator (genetics), Monocyte, Intracellular Signaling Peptides and Proteins, NF-kappa B p50 Subunit, Hematology, Flow Cytometry, Recombinant Proteins, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, Immunology, RNA Interference, Tumor necrosis factor alpha, medicine.symptom, Signal transduction, business, Signal Transduction

الوصف: SummaryPathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c3f92fda2c77162bcb106a8fcdfc1b8Test
https://doi.org/10.1160/th15-04-0322Test

المؤلفون: Bei, Jun-Jie, Liu, Chuan, Peng, Song, Liu, Cheng-Hai, Zhao, Wei-Bo, Qu, Xiao-Long, Chen, Qiang, Zhou, Zhou, Yu, Zheng-Ping, Peter, Karlheinz, Hu, Hou-Yuan

المساهمون: National Natural Science Foundation, Essential Drug Research and Development

المصدر: Thrombosis and Haemostasis ; volume 115, issue 03, page 632-645 ; ISSN 0340-6245 2567-689X

الوصف: Summary Pathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activates human platelets and induces generation of platelet microparticles (PMPs). Flow cytometry and scanning electron microscopy studies demonstrate that SSL5-induced PMPs (SSL5-PMPs) bind to monocytes, causing aggregate formation. In addition, SSL5-PMPs provoke monocyte expression and release of inflammatory mediators, including interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. SSL5-PMPs also enhance MCP-1-induced monocyte migration. Blockade of CD40 and CD40 ligand (CD40L) interactions with neutralising antibodies significantly reduce monocyte release of inflammatory mediators and migration induced by SSL5-PMPs. SiRNA-mediated silencing of CD40 or TNF receptor (TNFR)-associated factor 6 (TRAF6) gene largely abrogates phosphorylation and nuclear translocation of NFkB (p65). In conclusion, SSL5 provokes the release of inflammatory mediators in monocytes, at least in part, via PMPs-mediated activation of the CD40/TRAF6/NFkB signalling pathway, though it normally inhibits leukocyte function. Our findings thus reveal a novel mechanism by which S. aureus induces inflammation.

الإتاحة: https://doi.org/10.1160/th15-04-0322Test

المؤلفون: J. D. Phillipson, Zheng-Ping Chen, Ya Cai

المصدر: Planta Medica. 60:541-545

مصطلحات موضوعية: Pharmacology, biology, Traditional medicine, Croton lechleri, Organic Chemistry, Pharmaceutical Science, Biological activity, biology.organism_classification, In vitro, Analytical Chemistry, Endothelial stem cell, Complementary and alternative medicine, Drug Discovery, Molecular Medicine, Cytotoxic T cell, Cytotoxicity, Wound healing, Antibacterial agent

الوصف: Three in-vitro assays have been adopted to examine the cytotoxicity and anti-bacterial activity of the blood-red sap of Croton lechleri from Ecuador, and to examine its effect upon the proliferation of endothelial cells. The sap was found not to be cytotoxic. Several simple phenolic compounds and diterpenes showed a potent anti-bacterial activity. The sap has little effect upon the proliferation of endothelial cells, and no single active ingredient was identified. A mechanism for the wound-healing property of the sap has been proposed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b6744b66782b59353364eda0b972e30eTest
https://doi.org/10.1055/s-2006-959567Test

المؤلفون: Zheng, Ping, Dean, Jurrien

المصدر: Seminars in Reproductive Medicine ; volume 25, issue 4, page 243-251 ; ISSN 1526-8004 1526-4564

الإتاحة: https://doi.org/10.1055/s-2007-980218Test