Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1b production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIP L is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1b. Hemizygotic deletion of c-FLIP impaired ATP-and monosodium uric acid (MSU)-induced IL-1b production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1b expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-a was not affected by downregulation in c-FLIP. c-FLIP L interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1b generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIP L in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by overactivation of inflammasomes.
We studied the spatial and temporal expression of BDNF immunoreactivity and mRNA in the hippocampal formation after transient forebrain ischemia in gerbils. Our study demonstrated that in the vulnerable CA1 neurons, there was a prolonged expression disparity between BDNF immunoreactivity and mRNA and the BDNF level was reduced, in contrast to the ischemia-resistant dentate gyrus neurons that showed transient expression disparity and maintained the BDNF level. This expression disparity of the neurotrophic factor may be related to delayed neuronal death. Double immunostaining showed that reactive astroglia and microglia could express BDNF, suggesting a possible involvement of these cells in the mechanism of neuronal survival after ischemia.
A 32 nm BEOL with PVD CuMn seedlayer and conventional PVD-TaN/Ta liner was fully characterized by fundamental, integrated, and reliability methods. CuMn was confirmed to have fundamental advantages over CuAl, such as higher electromigration (EM) reliability for the same Cu line resistance (R). Both low R and high reliability (EM, SM, and TDDB) were achieved. Improved extendibility of CuMn relative to CuAl was also supported by studies of alloy interactions with advanced liner materials Ru and Co, and by enhancement of ultra-thin TaN barrier performance.
Background: There have been numerous reports evaluating clinical outcomes of implants placed in institutional settings, but there are few studies relating to implants placed in private practice. The aim of this retrospective study was to analyse the clinical outcomes of 1000 consecutively placed Straumann implants in private specialist periodontal practice. Methods: A hand-search of patient records was undertaken to identify 1000 consecutively placed implants. Data extracted included patient demographics, details of implants placed, implant sites, timing of placement after extraction, hard and soft tissue augmentation procedures, loading protocols, type of prostheses and treatment outcomes (implant survival, implant success and complications). Results: The majority of implants (71.5 per cent) placed in patients aged 40 to 69, and the majority of patients (88.6 per cent) received 1 or 2 implants. During the period of the study, 9 implants were lost and 45 presented with complications requiring chairside intervention. A life table analysis showed 5 and 10-year cumulative survival rates of 99.2 per cent and 98.4 per cent respectively, and 5 and 10-year cumulative success rates of 93.1 per cent and 90.9 per cent respectively. Conclusions: With careful treatment planning and adherence to recommended surgical and prosthetic protocols, high implant survival and success rates can be achieved in a private practice setting.
This abstract was withdrawn by the authors.
Citation Format: Huang C-S, Fann JC-Y, Chen H-H, Hsu G-C, Ho M-F, Chen S-C, Chen Y-J, Chen S-T, Chen C-Y, Sheen-Chen S-M, Chang H-T, Yeh D-C, Chao M, Yeh H-T, Cheng L, Chen D-R, Chang Y-C, Chang K-J. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-13.
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