Desulfurdioxidative N-N Coupling of N-Arylhydroxylamines and N-Sulfinylanilines: Reaction Development and Mechanism.

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good reaction yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO2.

Hepatocyte nuclear factor 4α induces a tendency of differentiation and activation of rat hepatic stellate cells.

AIM: To investigate the effect of hepatocyte nuclear factor 4α (HNF4α) on the differentiation and transformation of hepatic stellate cells (HSCs). METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4α shRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes. RESULTS: With increased expression of HNF4α mediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells (98.33 ± 12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated (G-P-6: 14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10 ± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type I collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression, EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated. CONCLUSION: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatment of liver diseases.

Twist2 is a valuable prognostic biomarker for colorectal cancer.

AIM: To investigate the significance of Twist2 for colorectal cancer (CRC). METHODS: In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients' clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox's proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. RESULTS: Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026). CONCLUSION: Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV.

Meta-analysis of simultaneous versus staged resection for synchronous colorectal liver metastases.

AIM: There is no clear consensus on the optimal timing of surgical resection for synchronous colorectal liver metastases (SCLM). This study is a meta-analysis of the available evidence. METHODS: Systematic review and meta-analysis of trials comparing outcomes following simultaneous resection with staged resection for SCLM published from 1990 to 2010 in PubMed, Embase, Ovid and Medline. Pooled odds ratios (OR) or weighted mean differences (WMD) with 95% confidence intervals (95% CI) were calculated using either the fixed effects or random effects model. RESULTS: Nineteen non-randomized controlled trials (NRCT) studies were included in this analysis. These studies included a total of 2724 patients: 1116 underwent simultaneous resection and 1608 underwent staged resection. Meta-analysis showed that shorter hospital stay (P < 0.001) and lower total complication rate (P < 0.001) were observed in patients undergoing simultaneous resection group. The overall survival rate in the simultaneous resection group did not statistically differ with that in the staged resection group at 1 year (P = 0.13), 3 years (P = 0.26), 5 years (P = 0.38), as well as the 1, 3 and 5 years disease-free survival rates (respectively, P = 0.55; P = 0.16; P = 0.12). No significant difference was noted between the two groups in terms of mortality (P = 0.16), intraoperative blood loss (P = 0.06) and recurrence (P = 0.47). CONCLUSION: Simultaneous resection is safe and efficient in the treatment of patients with SCLM while avoiding a second laparotomy. In selected patients, simultaneous resection might be considered as the preferred approach. However, the findings have to be carefully interpreted due to the lower level of evidence and the existence of heterogeneity.

[Separation and identification of Taxol in the crude extracts of Taxus cuspidata and its callus culture with HPLC-ESI-MS/MS].

AIM: To study the MS/MS fragmentation mechanism of Taxol, and based on it to establish HPLC-ESI-MS/MS technique to separate and identify Taxol in the crude extracts of Taxus cuspidata and its callus culture, consequently to provide a fast and credible method for the analysis of Taxol in natural products. METHODS: Optimized the HPLC-ESI-MS/MS parameters for the sample analysis, and then discussed the ionization and cleavage mechanism of Taxol in ESI-MS and ESI-MS/MS, finally identified the Taxol in the samples with retention time, molecular weight and MS/MS spectra. RESULTS: Elucidated the MS/MS fragmentation mechanism of Taxol, and developed HPLC-ESI-MS/MS method to analyze Taxol in the two samples. CONCLUSION: The HPLC-ESI-MS/MS method is rapid, highly sensitive and specific, so it is suitable for the separation and identification of Taxol in natural products.