ABSTRACT
Abstract Background: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result: When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.
ABSTRACT
<p><b>OBJECTIVE</b>To analyse the clinical and angiographic characteristics of spontaneous reperfusion (SR) in AMI, and to evaluate its effect on short-term prognosis.</p><p><b>METHODS</b>112 consecutive AMI patients without intravenous thrombolytic therapy received emergent coronary angiography and primary PCI. The patients were divided into SR group (antegrade TIMI grade 2-3 flow) and non-SR group (antegrade TIMI grade 0-1 flow). The clinical, angiographic and prognostic features of the patients were analyzed.</p><p><b>RESULTS</b>31 patients (27.7%) were in SR group, and there was no significant difference in base-line clinical characteristics between the two groups. Compared with non-SR group, peak values of CK and CK-MB, Ventricular wall motion abnormality and mortality were lower in SR group, ejection fraction was higher in SR group. Logistic regression analysis showed that there was good correlation between SR and peak value of CK, collaterals, ventricular wall motion abnormality and pre-dilation in PCI.</p><p><b>CONCLUSION</b>SR decreased infarction size, improved heart function and reduced 30-day mortality.</p>
Subject(s)
Aged , Humans , Male , Middle Aged , Angioplasty, Balloon, Coronary , Coronary Angiography , Myocardial Infarction , Diagnosis , Diagnostic Imaging , Therapeutics , Myocardial Reperfusion , Prognosis , Remission, SpontaneousABSTRACT
During the morphogenesis of the hindlimb and the digits of the rat, apoptosis has a crucial role to make their normal shape. In this study, apoptotic changes of the hindlimb from GD 13.5 to GD 17.5 were observed and compared with 5 -FU treated group to reveal the mechanism of teratogenic action of 5 -FU. The results were as follows; 1. The mean body weight of rat fetuses was decreased significantly in the 5 -FU treated group. 2. Congenital anomalies of the hindlimb digits were cleft foot, syndactyly and short digits, and the occurance rate of congenital anomalies was 58.1%, in which right -sided anomalies was 49.1% and left -sided anomalies was 18.9%. 3. Normal morphogenesis of the hindlimb digits was as follows; initially, hindlimb bud appeared at the lateral wall of lumbar somite on GD 10.5, grown as an elliptical mass proximodistally on GD 13.5, flattening and digital rays formation on GD 14.5, interdigital notches appeared on GD 15.5, interdigital spaces formation and interphalageal joints formation on GD 16.5, and deepening of interdigital spaces and elongation of digits on GD 17.5. 4. 5 -FU inhibited differentiation and growth of hindlimb bud initially, but its effect on development of hindlimb was disappeared after GD 15.5. According to the above results, it is considered that 5 -FU has an inhibitory effect on differentiation and growth of hindlimb of rat fetuses, and the TUNEL immunohistochemical method is much available to detect normal morphogenesis of an organ and to detect the mechanism of action of various teratogens.