Bell Nymand (warliquid2)

Serious infections in SLE are common and have emerged as the major cause of death. However, effective methods to identify poor prognosis are still lacking. Therefore, we aimed to determine the predictive value of C reactive protein (CRP) plus albumin (ALB) in SLE with serious infections. From May 2015 to December 2018, consecutive patients with SLE presenting with serious infections in our emergency department were prospectively recruited. Serum CRP and ALB were measured within 24 hours of admission. The outcome was defined as mortality rate at 90 days. A CRP plus ALB score (2-6) was assigned based on the CRP and ALB concentrations. We performed univariate and multivariate regression analyses to detect the independent effects of CRP plus ALB on 90-day mortality (all-cause and infection-related). Subgroup analyses were used to show the effects stratified by lupus nephritis. A total of 150 patients were included, and the all-cause 90-day mortality rate was 38% (n=57), 41 of which was infection-related. The predominant infection sites were pulmonary (79.3%) and bloodstream infection (20.7%). Serum CRP and ALB levels were significantly different in non-surviving patients compared with those in surviving patients (p=0.002 and p<0.001, respectively). In the fully adjusted logistic regression model, the CRP plus ALB score was associated with decreased 90-day survival (adjusted OR 1.52; 95% CI 1.08 to 2.13; p=0.017). CRP plus ALB was associated with the risk of all-cause and infection-related 90-day mortality in SLE with serious infections. Dihexa in vivo Although this finding requires further verification, the two parameters may be useful for predicting poor outcomes in such patients. CRP plus ALB was associated with the risk of all-cause and infection-related 90-day mortality in SLE with serious infections. Although this finding requires further verification, the two parameters may be useful for predicting poor outcomes in such patients.Our previous studies have shown that cathepsin L (CTSL) is involved in the ability of tumors to resist ionizing radiation (IR), but the specific mechanisms responsible for this remain unknown. We report here that mutant p53 (mut-p53) is involved in IR-induced transcription of CTSL. We found that irradiation caused activation of CTSL in mut-p53 cell lines whereas there was almost no activation in p53 wild-type (wt-p53) cell lines. Additionally, luciferase reporter gene assay results demonstrated that IR induced the p53 binding region on the CTSL promoter. We further demonstrated that the expression of p300 and Egr-1 was up-regulated in mut-p53 cell lines after IR treatment. Accordingly, the expression of Ac-H3, Ac-H4, AcH3K9 was up-regulated after IR treatment in mut-p53 cell lines, while HDAC4 and HDAC6 were reciprocally decreased. Moreover, knockdown of either Egr-1 or p300 abolished the binding of mut-p53 to the promoter of CTSL. ChIP assay results showed that the IR-activated transcription of CTSL was dependent on p300. To further delineate the clinical relevance of interactions between Egr-1/p300, mut-p53 and CTSL, we accessed primary tumor samples to evaluate the relationships between mut-p53, CTSL and Egr-1 /p300 ex vivo. The results support the notion that mut-p53 is correlated with CTSL transcription involving the Egr-1/p300 pathway. Taken together, the results of our study revealed that p300 is an important target in the process of IR induced transcription of CTSL, which confirms that CTSL participates in mut-p53 gain of function. Significance Statement Transcriptional activation of cathepsin L by ionizing radiation required the involvement of mutated p53 and Egr-1/p300. Interference with Egr-1 or p300 could inhibit the expression of cathepsin L induced by ionizing radiation. The transcriptional activation of cathepsin L by p300 may be mediated by p53 binding sites on the cathepsin L promoter.Current therapies for gastroparesis, metoclopramide