ABSTRACT
10,11-Dehydrocurvularin (DCV) is a natural-product macrolide that has been shown to exert anti-inflammatory activity. However, the underlying mechanism of its anti-inflammatory activity remains poorly understood. Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases, which should be controlled. The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1β secretion and caspase-1 activation, without effect on the NLRC4 and AIM2 inflammasomes. Furthermore, DCV disturbed the interaction between NEK7 and NLRP3, resulting in the inhibition of NLRP3 inflammasome activation. The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV. Importantly, DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome. Taken together, our study reveals a novel mechanism by which DCV suppresses inflammation, which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.
Subject(s)
Animals , Mice , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Interleukin-1beta/genetics , Mice, Inbred C57BLABSTRACT
Objective:To investigate the esophageal microecology in patients with esophageal carcinoma (EC), and to compare the difference in esophageal flora between patients with esophageal cancer and healthy people.Methods:From July 2018 to July 2019, at Taihe Hospital, 82 EC patients and 20 age-and gender-matched healthy controls during the same period were selected. The pathology of EC were divided into poorly differentiated (8 cases), moderately differentiated (9 cases) and well differentiated cancers (13 cases) according to the degree of differentiation. The esophageal tissue samples of EC patients and healthy individuals were collected. Sample DNA was extracted and the V4 region of bacterial 16S rRNA was amplified by polymerase chain reaction (PCR). Sequencing was performed by lllumina HiSeq 4000 sequencing platform. Alpha-diversity analysis and principal co-ordinates analysis (PCoA) were performed, and linear discriminant analysis (LDA) of linear discriminant analysis effect size (LEfSe) was used to screen different species. The random forest model was verified by receiver operating characteristic (ROC) curve and the esophageal bacterial phenotype was predicted by BugBase database. Non-parametric Kruskal-Wallis H test and Wilcoxon rank sum test were used for statistical analysis. Results:The Chao1 index of the EC patients was higher than that of healthy controls (362.51(284.29, 646.13) vs. 284.83(244.31, 344.74)), and the difference was statistically significant ( Z=-2.857, P=0.004). The results of PCoA showed that the distance between samples of EC patients and healthy control samples was relatively close, and there was no significant difference in the composition of microecology between the two groups ( P>0.05). The abundance of esophageal Cyanobacteria and Verrucomicrobia of EC patients were both higher than those of healthy controls (0.2% vs. 0.1%, 0.4% vs. 0), while the abundances of esophageal Proteobacteria, SR1 and TM7 phylum of EC patients were lower than those of healthy controls (21.9% vs. 34.2%, 0.1% vs. 0.2%, 0.2% vs. 0.5%), and the differences were statistically significant ( Q=0.090, 0.077, 0.010, 0.026 and 0.001, all P<0.05). The abundances of Clostridia, Elostridiales, Pasteurella, Pasteurellaceae, Eikenella, Actinobacillus and Haemophilus in poorly differentiated patients, moderately differentiated and higher differentiated patients were 28.3%, 24.2% and 17.0%, 28.3%, 24.2% and 17.0%, 3.2%, 0.3% and 5.0%, 3.2%, 0.3% and 5.0%, 0, 1.5% and 0.1%, 0.5%, 0 and 0.7%, 1.3%, 0.2% and 3.9%, respectively, and the differences were statistically significant ( Q=0.579, 0.557, 0.390, 0.711, 0.768, 0.768 and 0.768, all P<0.05). LEfSe analysis showed that the abundances of Fusobacterium, Ruminococcus, Odorbacterium and S24_7 of EC patients were higher than those of healthy controls (21.5% vs. 11.7%, 0.5% vs. 0.1%, 0.1% vs. 0 and 0 vs. 0), and the differences were statistically significant (LDA=2.591, 2.379, 2.790 and 2.927, all P<0.05). The ROC curve confirmed that the random forest model was reliable and the AUC value was 0.92. BugBase database phenotypic prediction showed that the phenotype of esophageal bacteria related to biofilm formation, pathogenic potential, mobile elements, oxygen demand (aerobic, anaerobic and facultative bacteria), and oxidative stress tolerance of EC patients were more abundant than those of healthy controls (all P<0.05). Conclusions:The esophageal flora of patients with esophageal cancer has changed. Fusobacterium, Ruminococcus, Odoribacterium and S24_7 may be potential biomarkers of esophageal flora.
ABSTRACT
OBJECTIVE:To investigate effects of ubiquitin-proteasome inhibitor MG-132on apoptosis and survivin expression of esophageal carcinoma cells.METHODS:The esophageal carcinoma cells Eca9706were treated with MG-132,the growth inhibitory rate was determined with MTT assay,apoptosis was detected by flow cytometry,expression of survivin was detected by immunocytochemical technique.RESULTS:MG-132had obvious inhibitory effects on the growth of gastric car?cinoma cells,IC 50 of24hrs,48hrs,72hrs and96hrs were120.2,18.1,—12.2,and—16.9?mol/L respectively;Treated with5.0?mol/L MG-132for24hrs,48hrs,72hrs and96hrs,apoptotic rates of cells were(3.1?0.4)%、(31.7?3.5)%、(50.4?4.8)%and(66.6?6.2)%respectively;Expression of survivin was high in esophageal carcinoma cells and it was decreased in cells treated with MG-132.CONCLUSIONS:MG-132can significantly inhibit the proliferation of esophageal carcinoma cells and induce apoptosis,which might be associated with down-regulated expression of survivin.
ABSTRACT
Objective To investigate the diagnostic significance of cytology and telomerase activity in the exfoliated cells of cardia obtained from endoscopic brushing in the cardiac cancer.Methods The technique of the qualitative TRAP siver staining and quantitative TRAP PCR ELISA were employed to detect telomerase activity in the exfoliated cells of cardiac obtained from endoscopic brushing in 72 cases with cardial lesions,cytological diagnosis was made at the same time.Results Telomerase activity with cardiac cancer group(1^521?0^192)was significantly higher than that with cardialitis group(0^065?0^014).Positive rate of telomerase activity detected in cardiac cancer group(88^89%)was significantly higher than that with cardialitis group(11^11%).Positive rate of telomerase activity detected in cardiac cancer group(88^89%)was significantly higer than cytological examination(77^78%).The diagnostic rate of cardiac cancer was improved to 93^33% if telomerase activity and cytology were examined at the same time.Conclusion Results show that the combination of cytology and telomerase activity in the exfoliated cardiac cells may be an effective and sensitive method in the diagnosis of cardiac cancer.This research can be a basis for the mass screening of cardiac cancer.
ABSTRACT
Objective Objective To study the influence of NS-398,a selective cyclooxygenase-2 inhibitor on the radiosensitivity of human esophageal carcinoma cell line EC9706 cell. Methods EC9706 cell, highly expressing COX-2, had been incubated with NS-398 at 10、20、50 and 100??mol/L for 24?h or 48?h before irradiation ranging from 0 to 10?Gy. Cell survival was measured by a standard clonogenic assay after 8 days of incubation. Apoptotic percentage was measured by FCM and DNA fragmentation by agarose electrophronesis. Results The senstization enhancement ratios (ratio of D_q) in EC9706 cell were 1.11, 1.24, 1.40, 1.54 at 10, 20, 50, 100??mol/L of NS-398 for 24?h pre-incubation and 1.11, 1.27, 1.58, 1.67 for 48?h pre-incubation, which showed a dose-dependant and time-dependant manner. FCM analysis revealed a higher sub-G_1 cell peak in NS-398 group after irradiation. Agarose electrophronesis showed a marked ladder. Radiation-induced apoptosis was enhanced by NS-398 (P