Matrix metalloproteinases in lung biology

Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease

Leptospirosis in French Polynesia: 11 years of surveillance data, 2007–2017

International audienc

Outcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients

Aim: The aim of this study was to evaluate the new World Health Organization (WHO) 2017 grading system and the others clinicopathological factors in pancreatic neuroendocrine tumor (panNET) operated patients. Methods: Histological staging was based on the WHO 2017 grading system. Outcome after surgery and predictors of overall survival (OS) and disease free survival (DFS) were evaluated. Results: A total of 138 patients underwent surgical resection with a severe morbidity and mortality rates of 14.5% and 0.7% respectively. Five years OS differed according to WHO 2017: 95% among 58 patients with NETG1, 82% in 68 patients with NETG2, 35% in 7 patients with NETG3 and 0% in 5 patients with NECG3 (P 60 y.o (P=0.014), synchronous metastasis (P=0.005) and WHO 2017 with significant differences between NETG1 versus NETG2 (P 0.005), NETG3 (P < 0.001) and NECG3 (P < 0.001). Independent predictors of worse DFS were symptomatic NET (P=0.038), pN+ status (P=0.027) and WHO 2017 with significant differences between NETG1 versus NETG3 (P=0.014) and NECG3 (P=0.009). Conclusion: The WHO 2017 grading system is a useful tool for patient prognosis after panNET resection and the tailoring of therapeutic strategy. Surgery could provide good results in NETG3 patients. (C) 2019 Elsevier Masson SAS. All rights reserved

Expression of recombinant proteins in a lipid A mutant of Escherichia coli BL21 with a strongly reduced capacity to induce dendritic cell activation and maturation

Mutations in the Escherichia coli (E. coli) and Salmonella lpxM gene have been shown to result in strains which grow normally and which produce a non-myristoylated lipopolysaccharide (nmLPS) with strongly reduced endotoxicity. Using homologous recombination, we inactivated the lpxM gene in BL21 (DE3), a strain widely used for the production of recombinant proteins. This led to a derivative unaffected in its capacity to support the production of recombinant proteins. This new strain expresses non-myristoylated LPS that induces markedly less activation and maturation of monocyte-derived dendritic cells (DC), as assessed by nuclear translocation of nuclear factor kappa B (NF-kappaB), production of TNF-alpha and IL-8 or expression of CD86. Activation of the main signal transducing receptor for extracellular LPS, Toll like receptor (TLR) 4 in conjunction with the soluble accessory protein MD-2 was also markedly decreased.The modified BL21 strain represents a new application of lpxM inactivation for the expression of proteins to be tested on dendritic cells or other LPS sensitive cells/receptor complexes. It is likely to be useful for the identification of new proteins activating the innate immune response and to reducing the risk linked with low level of endotoxin contamination in therapeutic recombinant proteins