374,761 research outputs found
Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation
No full textCellular 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-1 beta production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIPL is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1 beta. Hemizygotic deletion of c-FLIP impaired ATP-and monosodium uric acid (MSU)-induced IL-1 beta production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1 beta expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-alpha was not affected by downregulation in c-FLIP. c-FLIPL 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-1 beta generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIPL 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 over-activation of inflammasomes
Direct Regulation of Hsp60 Expression by C-Myc Induces Transformation
No full textThe c-MYC proto-oncogene encodes a ubiquitous transcription factor involved in cell proliferation and tumorigenesis. Heat shock protein 60 ( HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in different types of human cancer. Here we show that c-MYC directly activates HSP60 transcription through an E-box ( CACGTG) site located in the proximal promoter of the HSP60 gene. Overexpression of HSP 60 induces transformation. Short- interference RNA (siRNA) mediated repression of HSP60 reduces transformation caused by c-MYC overexpression. These results indicate that c-MYC may promote transformation through the induction of HSP60 expression
MPTP/MPP+ suppresses activation of protein C in Parkinson's disease
No full textEndothelial dysfunction and disruption of the blood-brain barrier have been found to be associated with Parkinson's disease (PD). However, the mechanisms underlying these effects have yet to be elucidated. It has also been found that activated protein C (APC) displays neuroprotective properties. Presently, the effects of APC on PD remain unknown. Using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxin rodent model of PD, we found that administration of MPTP can reduce expression of endothelial protein C receptor (EPCR), an N-glycosylated type I membrane protein that has the ability to enhance protein C activation. However, the use of MPTP does not alter levels of thrombomodulin. These findings were verified in an in vitro study showing that 1-methyl-4-phenylpyridinium (MPP+) treatment leads to suppression of EPCR along with reduction of protein C activation in human primary endothelial cells. Importantly, our results display that activation of the transcriptional factor SP1 is involved in the inhibitory effects of MPTP/MPP+ on EPCR expression. We found that using 300 nM of the SP1 inhibitor MIT can abolish the effects of MPP+ on EPCR expression. Consistently, SP1 silencing using small RNA interference was able to prevent the inhibitory effects of MPTP/MPP+ on the reduction of EPCR expression and impairment of protein C activation. Importantly, our results indicate that overexpression of SP1 inhibits EPCR promoter activity. Our study suggests that EPCR-APC may be a potential therapeutic target for endothelial dysfunction in P
Molecular structure of highly excited resonant states in Mg-24 and the corresponding Be-8+O-16 and C-12+C-12 decays
No full textExotic Be-8 and C-12 decays from high-lying resonances in Mg-24 are analyzed in terms of a cluster model. The calculated quantities agree well with the corresponding experimental data. It is found that the calculated decay widths are very sensitive to the angular momentum carried by the outgoing cluster. It is shown that this property makes cluster decay a powerful tool to determine the spin as well as the molecular structures of the resonances.Physics, NuclearSCI(E)7ARTICLE5null8
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Propolin C from Propolis Induces Apoptosis through Activating Caspases, Bid and Cytochrome C Release in Human Melanoma Cells
No full textWe had demonstrated that two prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced apoptosis in human melanoma cells and significantly inhibited xanthine oxidase activity . Here, we have isolated a third compound called propolin C. The chemical structure of propolin C has been characterized by NMR and HRMS spectra, and was identical to nymphaeol-A. However, no biological activities of this compound have ever been reported. In the present study, propolin C effectively induced a cytotoxic effect on human melanoma cells, with an IC 50 of about 8.5 muM. DNA flow cytometric analysis indicated that propolin C actively induced apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of propolin C, we evaluated the effect of propolin C on induction of apoptosis -related proteins in human melanoma cells. The levels of procaspase-8, Bid, procaspase-3, and poly( ADP-ribose) polymerase were decreased in dose- or time course-dependent manners. Moreover, propolin C was capable of releasing cytochrome c from mitochondria to cytosol. The findings suggest that propolin C may activate a mitochondria-mediated apoptosis pathway. On other hand, propolin C is a potential antioxidant agent and shows a strong capability to scavenge free radicals and inhibit on xanthine oxidase activity with IC50 of about 17.0 muM. In conclusion, the isolation and characterization of propolin C from bee propolis are described for the first time, and this compound is a powerful inducer of apoptosis in human melanoma cells. (C) 2003 Elsevier Inc. All rights reserved
B -> eta K-c(eta ' K-c) decays in QCD factorization
No full textWe study the exclusive decays of the B meson into pseudoscalar charmonium states eta(c) and eta(c)' within the QCD factorization approach and find that the non-factorizable corrections to naive factorization are infrared safe at leading-twist order. The spectator interactions arising from the kaon twist-3 effects are formally power suppressed but chirally and logarithmically enhanced. An important improvement by including the O(alpha(s)) corrections is the cancellation of the renormalization scale mu dependence of the decay amplitude. However, the calculated decay rates are too small to accommodate the experimental data. On the other hand, we compare the theoretical calculations for B meson decays to J/psi, psi', eta(c) and eta'(c), and find that the predicted relative decay rates of these four states are approximately compatible with the experimental data.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000223097800007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Physics, Particles & FieldsSCI(E)17ARTICLE3365-3703
Electrochemical Detection of High-Sensitivity C-Reactive Protein Based on Biomimic Design of Electroactive Nanoassembly Multilayers
No full textIn this study, the gold electrode was modified with a ferrocene-terminated alkanethiol and phospholipid complex layer, which is designed and fabricated to serve as a C-reactive protein sensor using electrochemical determination. The scope of this research is to know whether a ferrocene-terminated self-assembled monolayer and hydrogenated phosphocholine hybrid bilayer could be used to perform C-reactive protein detection or not. After a series of experiments, the result shows that mixed electroactive SAM can facilitate electrons transferring from the solution to the electrode. And after coating phospholipids, this phenomenon seems to be hindered from the electrode. But this provoked small electrical signal of the recognition layer still allows for further usage. According to the result, it can be used to measure C-reactive protein and its electrochemical property and the changes of the electrode's electron transfer ability are characterized by cyclic voltammetry. This study demonstrates self-assembled ferrocene-terminated alkanethiol and phospholipid complex structure has potential as a C-reactive protein sensor and is stable to detect in the aqueous phase.補正完
History sketch 157th Engineer (C) Bn.
No full textThis is a historical description of the 157th Engineer (C) Battalion written from memory by author. Notes are not attached as described on last page of document
Wu Rongfu and Wu Decai talking about Temples in Mianning
No full textWu Decai and Wu Rongfu talk about local Mianning temples (Lingshansi), recall visiting temples in their youth, and about temples nowadaysEquipment: Fostex Fr-2 AKG C 480 B+CK61-ULS (cardiod
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