Construction of CeRNA regulatory network based on WGCNA reveals diagnosis biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the third most common cause of death among cancers in the world. Although improvements in various treatments have greatly improved the survival time of colorectal cancer patients, since colorectal cancer is often at an advanced stage when diagnosed, the prognosis of patients is still very poor. Since the ceRNA regulatory network was proposed in 2011, it has greatly promoted the study of the molecular mechanism of colorectal cancer occurrence and development. OBJECTIVE: Exploring the new molecular mechanism of colorectal cancer occurrence and development and providing new targets for the diagnosis and treatment of colorectal cancer. METHOD: We analyzed the RNA-seq data of CRC from TCGA, such as differential expression analysis, weighted gene co-expression network analysis (WGCNA) and construction of ceRNA regulatory network. RESULTS: We constructed a ceRNA network using RNA-seq data of CRC from TCGA. In the ceRNA regulatory network, 19 hub molecules with significant prognostic effects were ultimately identified, including 8 lncRNAs, 2 mRNAs and 9 miRNAs. These hub molecules constitute the lncRNA-miRNA, miRNA-mRNA or lncRNA-miRNA-mRNA axis. CONCLUSION: In this article, some new ceRNA regulatory axes have been discovered, which may potentially disclose new molecular mechanisms for the occurrence and development of colorectal cancer, thereby providing an important blueprint for the treatment and prognosis assessment of CRC patients.

Stereoselective Synthesis of Spiro Bis-C,C-α-arylglycosides by Tandem Heck Type C-Glycosylation and Friedel-Crafts Cyclization.

Spiro bis-C,C-α-arylglycosides were synthesized in three steps in 78-85% overall yields starting from exo-glycals. The initial Heck type C-aryl addition of exo-glycals with arylboronic acids afforded α-aryl-ß-substituted C-glycosides with exclusive α-stereoselectivity. Among the products, ß-ethanal α-aryl C-glycosides further reacted with alkylthiol in the presence of InCl3, followed by in situ Friedel-Crafts cyclization to yield the desirable final products. We proposed a mechanism to explain how the α-aryl group serves as a main determinant of the cyclization.

[Chemical Constituents and Sources of PM2.5 Around the Wuhan Military Games Period].

Hourly monitoring datasets of PM2.5 mass concentration and associated chemical compositions were used to investigate the variations in their mass concentrations before, during, and after the 7th Military World Games held in Wuhan. Furthermore, the source analysis was conducted through PMF combined with the backward trajectory and concentration weighted trajectory cluster analysis. The study revealed the variations in PM2.5 compositions and sources around the Wuhan Military Games period and their response to local and surrounding regional control measures. This can provide a reference for regional precise prevention and control of PM2.5. Under the influence of emission reduction measures, PM2.5 mass concentration during the control period [(31.3±12.0) µg·m-3] decreased by 14.7% compared with that before the control period, whereas the secondary components were obviously formed, in which sulfate, nitrate, and ammonium(SNA) increased by 25.6% in total. After the control period, owing to the decrease in humidity and the influence of the northwest air mass, the mass concentration of SNA decreased by 36.9%, whereas the mass concentration of mineral elements increased by 4.7 times. The source apportionment results indicated that there was no significant difference between the vehicle emissions before and after the control(P<0.05). Compared with that in the non-control period, the contributions of industrial emission and coal burning decreased by 68.1% and 43.7%, respectively, whereas the contribution of secondary inorganic aerosol increased by 89.5%. With the lack of large-scale control of vehicle emissions, the mass concentrations of NO3- and NOx increased by 6.13 µg·m-3 and 3.56 µg·m-3, respectively. The vehicle emissions peaked at 21:00 [(10.9±3.67) µg·m-3], reflecting the emissions of cargo vehicles, which were only allowed to pass at night during the control period. With the banning of ship navigation, the ship emission in the middle and lower reaches of the Yangtze River significantly decreased(48.8%). There were also high values of fugitive dust and industrial emissions near the Anhui section of the Yangtze River waterway, which reflected the dense distribution of industrial activities and road transportation along the Yangtze River. After the control period, the fugitive dust increased by 6.6 times, and the source areas were mainly distributed in Xiangyang and Jingmen.

FSTL1 increases cisplatin sensitivity in epithelial ovarian cancer cells by inhibition of NF-κB pathway.

OBJECTIVE: To investigate the effects of FSTL1-mediated NF-κB signaling pathway on cisplatin (DDP) sensitivity of EOC cells. METHODS: FSTL1 expression was determined in epithelial ovarian cancer (EOC) tissues and corresponding adjacent tissues using immunohistochemistry. SKOV3 and SKOV3/DDP cells were transfected and grouped into Blank, Vector, and FSTL1 groups. The sensitivity and 50% inhibitory concentration (IC50) of cells treated with different concentrations of DDP were detected by MTT assay. SKOV3/DDP cells were treated with 20 µM DDP, followed by evaluation of cell proliferation, cell apoptosis and determination of NF-κB pathway-related proteins while SKOV3 cells without. RESULTS: FSTL1 expression in EOC tissues and cells was significantly down-regulated, especially decreased in DDP-resistant EOC cells SKOV3/DDP. In SKOV3 cells and SKOV3/DDP cells, the cell viability was reduced and the DDP sensitivity was improved with the decreased IC50 after over-expressing FSTL1. Compared with Blank group, FSTL1 group had declined number of SKOV3 cell colonies and increased cell apoptosis, with obvious up-regulations of FSTL1, Bax/Bcl-2 and cleaved caspase-3 expression and the down-regulations of p-IκBα, p-p65 and survivin expression. Combination of up-regulation of FSTL1 and DDP treatment can also effectively reduce cell colony forming, increase cell apoptosis, and inhibit NF-κB pathway activity of SKOV3/DDP cells. Moreover, this combination can also significantly suppress the growth of subcutaneous xenograft tumors in nude mice. CONCLUSION: FSTL1 may inhibit NF-κB signaling pathway to suppress the growth and promote the apoptosis of epithelial ovarian cancer cells, and thereby enhancing its DDP sensitivity.

Low expression of FXYD5 reverses the cisplatin resistance of epithelial ovarian cancer cells.

OBJECTIVE: To investigate the effect of the downregulation of FXYD domain-containing ion transport regulator 5 (FXYD5) on the cisplatin resistance (CisR) of epithelial ovarian cancer (EOC) cells. METHODS: A2780-CisR and SKOV3-CisR cells were obtained through repeated administrations of different cisplatin concentrations, and the half-maximal inhibition concentration (IC50) was calculated by MTT assays. After transfection with FXYD5 siRNA-1 and FXYD5 siRNA-2, the IC50 values of the A2780-CisR and SKOV3-CisR cells were also detected by the MTT method. Cell proliferation, migration, invasion and apoptosis were evaluated through 5-ethynyl-2'-deoxyuridine (EdU) DNA synthesis, wound healing, Transwell invasion and Annexin-V-FITC/PI dual-staining assays, respectively. qRT-PCR and Western blotting were conducted to detect mRNA and protein expression. RESULTS: Compared with the sensitive parental cells, the A2780-CisR and SKOV3-CisR cells had increased IC50 and FXYD5 expression. FXYD5 siRNA reduced the IC50 value of cisplatin in the A2780-CisR and SKOV3-CisR cells and decreased the expression of ABCG2 (BCRP) and ABCB1 (MDR1). In addition, FXYD5 inhibition reduced the invasion and migration of the A2780-CisR and SKOV3-CisR cells, with upregulation of E-cadherin and downregulation of Snail and Vimentin. Both FXYD5 siRNA-1 and FXYD5 siRNA-2 inhibited the proliferation and promoted the apoptosis of the A2780-CisR and SKOV3-CisR cells with reduced Ki-67 and increased caspase-3. CONCLUSION: FXYD5 downregulation may reduce the invasion, migration and EMT formation of EOC cells to increase their sensitivity to cisplatin chemotherapy by inhibiting cell proliferation and promoting cell apoptosis.

Optimal antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: A systemic review and meta-analysis.

A challenge for antithrombotic treatment is patients who present with atrial fibrillation (AF) and acute coronary syndrome, particularly in patients who have undergone coronary percutaneous intervention with stenting (PCIS). In the present study, a total of nine observational trials published prior to July 2017 that investigated the effects of dual antiplatelet therapy (DAPT; aspirin + clopidogrel) and triple oral antithrombotic therapy (TOAT; DAPT + warfarin) among patients with AF concurrent to PCIS were collected from the Medline, Cochrane and Embase databases and conference proceedings of cardiology, gastroenterology and neurology meetings. A meta-analysis was performed using fixed- or random-effect models according to heterogeneity. The subgroups were also analyzed on the occurrence of major adverse cardiac events (MACE), stroke and bleeding events in the two treatment groups. Analysis of baseline characteristics indicated that there was no significant difference in the history of coexistent disease or conventional therapies between the DAPT and TOAT groups. The primary end point incidence was 2,588 patients in the DAPT group (n=13,773) and 871 patients in the TOAT group (n=5,262) following pooling of all nine trials. There was no statistically significant difference in the incidence of primary end points between the DAPT and TOAT groups. Odds ratio (OR)=0.96, 95% confidence interval (CI)=0.73-1.27, P=0.79, with heterogeneity between trials (I2=82%, P<0.00001). Subsequently, on subgroup analysis, the results indicated no increased risk of major bleeding or ischemic stroke in the DAPT or TOAT group. However, compared with the TOAT group, there was an apparent increased risk of MACE plus ischemic stroke in the DAPT group (OR=1.62, 95% CI=1.43-1.83, P<0.00001) with heterogeneity between trials (I2=70%, P=0.01). In conclusion, the present meta-analysis suggests that TOAT (aspirin + clopidogrel + warfarin) therapy for patients with AF concurrent to PCIS significantly reduced the risk of MACE and stroke compared with DAPT (aspirin + clopidogrel) therapy. Further randomized controlled clinical trials are required to confirm the efficacy of the optimal antithrombotic therapy in patients with AF following PCIS.

[Protection value evaluation of national wetland parks in Hunan Province, China]. / æ¹–å—çœå›½å®¶æ¹¿åœ°å ¬å›­ä¿æŠ¤ä»·å€¼è¯„ä»·.

This paper put forward an evaluation index system which included 5 aspects such as ecological location and representation, biodiversity, species rarity, naturality, scale and partition suitability as well as 15 indicators to assess the protection values of 60 national wetland parks in Hunan Province, China. Analytic hierarchy process (AHP) and entropy method were used in this evaluation index system. There were 37 national wetland parks (accounting for 61.7%) keeping high protection values with scores of greater than or equal to 67.64 points, and 12 national wetland parks (accounting for 20.0%) keeping very high protection values with scores of greater than or equal to 77.72 points. Although there was a discrete and rare regularity of the inter-annual variation, these values still showed a decreasing trend in general. From the space point of view, 70 points isogram divided the national wetland parks of Hunan Province into two high score areas and three high score points in the west and east area, and one low score area and four low score points in the middle. Ecological location, resource endowment and scale were the decisive factors for the conservation va-lues of national wetland parks in Hunan Province.