-
Wren Funch posted an update 6 months, 3 weeks ago
Increasing atmospheric concentration of N2O has been a concern, as it is a potent greenhouse gas and promotes ozone layer destruction. In the N-cycle, release of N2O is boosted upon a drop of pH in the environment. Here, Marinobacter hydrocarbonoclasticus was grown in batch mode in the presence of nitrate, to study the effect of pH in the denitrification pathway by gene expression profiling, quantification of nitrate and nitrite, and evaluating the ability of whole cells to reduce NO and N2O. At pH 6.5, accumulation of nitrite in the medium occurs and the cells were unable to reduce N2O. In addition, the biochemical properties of N2O reductase isolated from cells grown at pH 6.5, 7.5 and 8.5 were compared for the first time. The amount of this enzyme at acidic pH was lower than that at pH 7.5 and 8.5, pinpointing to a post-transcriptional regulation, though pH did not affect gene expression of N2O reductase accessory genes. N2O reductase isolated from cells grown at pH 6.5 has its catalytic center mainly as CuZ(4Cu1S), while that from cells grown at pH 7.5 or 8.5 has it as CuZ(4Cu2S). This study evidences that an in vivo secondary level of regulation is required to maintain N2O reductase in an active state.
Calprotectin is a heterodimer formed by S100A8 and S100A9 proteins which are enhanced during hepatic carcinogenesis and the increased expression of both proteins promotes malignant progression of hepatocellular carcinoma. IOX2 The potential correlation between ascitic Calprotectin and HCC was not studied.
100 patients were stratified into a case group which enrolled 50 patients with cirrhotic ascites and documented HCC and a control group consisted of 50 patients with cirrhotic ascites without HCC. They were evaluated by liver function tests, abdominal ultrasound and routine ascitic fluid examination including ascetic Calprotectin and results were validated in another group (n = 100).
Calprotectin level was significantly higher in the HCC group with insignificant difference regarding total cell count, PNLs, ascitic albumin, LDH, CEA and SAAG. It correlated with serum creatinine (r = 0.245, p = 0.014) and number of focal hepatic lesions (r = 0.309, p = 0.002). In the validation group, 28 patients had elevated ascitic Calprotectin of which 21 patients had developed HCC (75%) after a mean period of 3.8 ± 1.54months. A cut of value 126ng/ml was accurate to predict HCC in liver cirrhosis with ascites with a sensitivity of 93.3% specificity 94%, AUC 0.950, Youden’s J value = 0.873, p = 0.0001.
Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.
Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.
Radiotherapy is the mainstay for treating brain metastasis (BM). The objective of this study is to evaluate the overall survival (OS) of patients with BM of lung cancer treated with different radiotherapy modalities.
Patients with BM of lung cancer who underwent radiotherapy between July 2007 and November 2017 were collected, and their baseline demographics, clinicopathological characteristics and treatments were recorded. Survival was estimated by the Kaplan-Meier method and compared by using the log-rank test. Univariate and multivariate analysis of the prognostic factors were performed using the Cox proportional hazard regression model.
A total of 144 patients were enrolled, of whom 77 underwent whole-brain radiotherapy (WBRT), 39 underwent whole brain radiotherapy with consecutive boost (WBRT + boost), and 28 underwent integrated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). The OS in SIB-IMRT group was significantly longer than that in WBRT group (median OS 14 (95% confidence interval 8.8-19.1) vs.7 (95% CI 5.5-8.5) months, log-rank p < 0.001) and WBRT + boost group (median OS 14 (95% CI 8.8-19.1) vs.11 (95% CI 8.3-13.7) months, log-rank p = 0.037). Multivariable analysis showed that mortality risk of patients treated with SIB-IMRT decrease by 56, 59, 64 and 64% in unadjusted model (hazard ratio = 0.44; 95% CI 0.28-0.70, p < 0.001), model 1 (HR = 0.41; 95% CI 0.26-0.65, p < 0.001), model 2 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001), and model 3 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001).
For patients with BM of lung cancer, SIB-IMRT seems to be associated with a more favorable prognosis.
For patients with BM of lung cancer, SIB-IMRT seems to be associated with a more favorable prognosis.Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematological diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A, a known immunosuppressive agent, enhanced carfilzomib’s efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clinical management.