Search

The mechanism of the reaction of 1,3‐bis (amino)‐2‐phosphaallyl chlorides with hydrazine for the synthesis of 1H‐1,2,4‐diazaphospholes in CHCl3 solvent has been extensively investigated at the B3LYP/6‐311G (d, p) level. The reaction is initiated by the elimination of HCl and formation of a key intermediate A, then A subsequently undergoes H‐migration‐cyclization (A → B) and Me2NH elimination reactions (B → C) to afford carbene intermediate C, and C can transform to F along both single and triplet potential energy surfaces in three steps. H‐migration‐cyclization (A → B) step was identified as a proton‐coupled electron transfer (PCET) process, and singlet‐triplet PES crossing should be important in decomposition of C to D1 and D2. For R═Me, Ph and H, the rate control step should be the decomposition of C, while for R═tBu, the first Me2NH removal step is the rate control one. Theoretical results suggested that tBu is a preferable group than Ph, Me, and H in this reaction, which can be attributed to hyperconjugation effects of tBu, showing good agreement with experimental data. The mechanism of the reaction of 1,3‐bis(amino)‐2‐phosphaallyl chlorides with hydrazine for the synthesis of 1H‐1,2,4‐diazaphospholes in CHCl3 solvent has been extensively investigated at the B3LYP/6‐311G (d, p) level. Theoretical results suggested that tBu is a preferable group than Ph, Me, and H in this reaction, which can be attributed to hyperconjugation effects of tBu, showing good agreement with experimental data. [ABSTRACT FROM AUTHOR]

We performed a study to investigate the role of ERCC1, ERCC2, ERCC5, XPA and XPC polymorphisms from perspective of the whole NER pathway in the prognosis of gastric cancer. A total of 410 gastric cancer patients were recruited between January 2010 and December 2011. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to analyze genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and s1799793, ERCC5 rs17655, XPA rs1800975 and XPC rs2228001. Our study found that carriers of ERCC1 rs3212986 TT genotype showed significantly favorable survival than wide-type GG genotype in multivariate analysis (OR=6.38, 95% CI=2.54-19.03), and patients with variant CC genotype of ERCC2 rs13181 exhibited better response to chemotherapy than those with AA genotype (OR=2.21, 95% CI=1.17-4.25). By Cox proportional hazards model, patients with variant TT genotype of ERCC1 rs3212986 exhibited longer PFS and OS than those who had GG genotype (for PFS, HR=0.37, 95% CI=0.17-0.75; for OS, HR=0.36, 95% CI=0.13-0.87). For ERCC2 rs13181 polymorphism, carriers with CC genotype demonstrated significantly increased hazards of progression of disease and death in multivariate model (for PFS, HR=0.48, 95% CI=0.26-0.88; for OS, HR=0.44, 95% CI=0.20-0.91). In conclusion, our finding suggests that ERCC1 rs3212986 and ERCC2 rs13181 gene polymorphism could influence the response to chemotherapy and clinical outcome of gastric cancer.

Objective: To investigate the relationship between baseline heart rate(HR) and all-cause death(ACD)in general population., Methods: 93 716 workers with heart rate between 40 bpm/min-120 bpm/min and without histories of stroke were selected from the '2006-2007 health examination records' in Kailuan and completed the electrocardiogram exam. Related information were also gathered. These subjects were followed up from July 2006 to December 2010, with the mean time of follow-up as 47.5±4.3 months. During the follow-up period, the occurrence of all-cause death was observed every half a year., Results: (1)The lowest cumulative mortality rate was 1.61% in the group with 60-69 bpm/min. The lowest cumulative mortality rate was 1.78% in the group of 60-69 bpm/min in men. There was no death events observed in women with less than 50 bpm/min and the lowest cumulative mortality rate was 0.60% in the group of 80-89 bpm/min in women. (2)Data from Cox proportional hazard regression analysis showed that the RR(95%CI)of cumulative mortality rates in general population were 1.187 (1.039-1.336), 1.392(1.185-1.636), 1.733(1.404-2.139)and 2.716 (2.171-3.398)in the groups of 70-79, 80-89, 90-99 and ≥100 bpm/min, respectively. The RRs (95% CI) of cumulative mortality in men were 1.227(1.067-1.410), 1.481(1.254-1.750), 1.754 (1.406-2.188)and 2.831 (2.245-3.571) respectively. In women, when comparing with the group of 80-89 bpm/min, the RRs (95%CI)of all-cause death were 0.671(0.568-0.793), 0.825(0.703-0.970) and 1.925 (1.512-2.453)respectively in the groups of 60-69, 70-79 and ≥100 bpm/min., Conclusion: When HR exceeding ≥70 bpm/min, the increase of HR would also increase the rate of ACD. Results of our study also showed a J-shaped curve relation between HR and mortality.

Objective: To evaluate the efficacy of probiotics on the treatment outcomes of ulcerative colitis, and explore its possible mechanism., Methods: According to the table of random number, 60 ulcerative colitis patients in our hospital were enrolled prospectively and divided into 3 groups: Golden Bifid group, Changmei group, combination group (Golden+ Changmei). Patients in Golden Bifid group received Golden Bifid 2.0 g, bid, those in Changmei group received Changmei 1.0 g, tid, and those in combination group received the above two drugs for 24 months. The clinical symptom score, colon mucosa inflammation score and endoscopic grade score were calculated and compared. IL-10 in mucosa and serum was determined by immunohistochemistry and double-antibody sandwich ELISA., Results: In combined group after 24 months of treatment, clinical symptom score (12.5±2.1 vs. 2.3±0.8, P=0.016), endoscopic classification score (3.02±0.17 vs. 0.25±0.13, P=0.032), inflammatory reaction score (2.63±0.19 vs. 0.77±0.16, P=0.028) were significantly higher than those before treatment. While the scores differences of before and after treatment in Gold Bifid group and Changmei group were not statistically significant (P>0.05). IL-10 in serum [(17.4±2.2) ng/L vs. (12.8±2.2) ng/L, P=0.015] and colon mucosa [85% (17/20) vs. 55% (11/20), P=0.026] in combination group were significantly higher than those before treatment. The differences in IL-10 expression level before and after treatment were not statistically significant in the Gold Bifid group and Changmei group (P>0.05)., Conclusion: Golden Bifid combined with Changmei as microbial ecological agents has a positive efficacy on mild to moderate ulcerative colitis, which may be associated with the up-regulation of IL-10 expression.

Objective: To explore the effect of down-regulation of astrocyte elevated gene-1 (AEG-1) expression on cell proliferation and cell cycle of gastric carcinoma cells, and its possible molecular mechanism., Methods: Control siRNA and AEG-1 siRNA were transfected into gastric carcinoma SGC-7901 cells. 48 h after transfection, the cells were divided into 3 groups including untransfected, siRNA control and AEG-1 siRNA transfection groups. Expressions of AEG-1 mRNA and protein in the 3 group cells were detected by real-time quantitative PCR and Western blot. The changes of cell proliferation were examined using CCK-8 kit, and the cell cycle distribution was detected by flow cytometry. Finally, expressions of cell proliferation and cell cycle related proteins were detected by Western blot., Results: Real-time quantitative PCR and Western blot demonstrated that compared with the untransfected and siRNA control groups, expressions of AEG-1 mRNA and protein were significantly down-regulated in the AEG-1 siRNA transfection group (P < 0.05), but there was no significant difference between the untransfected and siRNA control groups (P > 0.05). Furthermore, in vivo experiment confirmed a significant down-regulation of AEG-1 protein in the AEG-1 siRNA transfection group (P < 0.05). In addition, AEG-1 siRNA obviously inhibited the proliferation of SGC-7901 cells at different time points after transfection with AEG-1 siRNA. The percentage of cells in G0/G1 phase in the AEG-1 siRNA transfection group [(61.26 ± 1.25)%] was significantly higher than those in the untransfected group [(46.17 ± 1.91)%] and siRNA control group [(46.46 ± 1.96)%], and there was a significant difference between them (all P < 0.001). Furthermore, the result of Western blotting revealed that down-regulation of AEG-1 expression evoked the down-regulation of cdk2 and cyclin D1 expressions and elevation of p21 expression in vitro and in vivo., Conclusions: The inhibition of cell proliferation and cell cycle arrest mediated by down-regulation of AEG-1 expression may be closely associated with the changes of expression of cell cycle related proteins including cdk2, cyclin D1 and p21.

Objective: To investigate the expression of KIAA0101 protein in gastric carcinoma cells, and to explore the effects of its down-regulation on the cell proliferation, cell cycle and invasion., Methods: Western blot was used to detect KIAA0101 protein expression in three gastric carcinoma cell lines including MKN-28, SGC-7901 and MKN-45. KIAA0101 siRNA and control siRNA were utilized to transfect MKN-45 cells, respectively. CCK-8 was used to analyze the changes of cell proliferation, and flow cytometry to examine the changes of cell cycle distribution. Finally, Boyden chamber was used to detect the ability of cell invasion., Results: Relative level of KIAA0101 protein in MKN-45 cells was significantly higher than those in MKN-28 and SGC-7901 cells, and there was significant difference among the three cell lines (P < 0.05). The result of CCK-8 study demonstrated that, compared with untreated group and control siRNA group, the proliferation of MKN-45 cells in KIAA0101 siRNA group was significantly inhibited (P < 0.05). Additionally, the result of cell cycle analysis revealed that the percentage of cell number in G(0)/G(1) phase in KIAA0101 siRNA group [(61.47 ± 0.89)%] was significantly higher than those in untreated group [(47.43 ± 0.85)%] and control siRNA group [(48.43 ± 0.73)%; F = 271.653, P = 0.000]. Further, Boyden chamber assay showed that the cell numbers migrated to Matrigel in KIAA0101 siRNA group (61.51 ± 4.76) were significantly lower than those in untreated group (138.74 ± 10.16) and control siRNA group (132.93 ± 11.25; F = 65.949, P = 0.000)., Conclusions: Down-regulation of KIAA0101 expression leads to an inhibition of cell proliferation, cell cycle and cell invasion. It may provide a novel target for the treatment of patients with gastric carcinoma.

Objective: To evaluate the siRNA-mediated inhibitory effect of nuclear factor-kappaB (NF-kappaB) p65 on expression of p65, and explore the effect of blockade of NF-kappaB signal pathway on cell apoptosis in cutaneous squamous cell carcinoma (cutaneous SCC)., Methods: Cutaneous SCC cell line SCL-1 cells were transfected with 50 nmol/L p65 siRNA. The expression level of p65 mRNA was measured using RT-PCR method at 0, 24, 48 and 72 h . Expressions of p65, bcl-2 and bax proteins were determined using Western blotting. Activities of caspase-3/9 was detected by Caspase-Glo®-3/7, 8 and 9 kit. Finally, cell apoptosis was detected using flow cytometry., Results: The expression level of p65 mRNA in Cutaneous SCC SCL-1 cells was obviously down-regulated 48 h after transfection with p65 siRNA, and a significant difference was detected, as compared with 0 h after (0.23 ± 0.10 vs. 0.66 ± 0.05, P<0.05). The protein levels of p65 and bcl-2 decreased, and the bax protein level and activities of caspase-3/9 increased after transfection with p65 siRNA at h 48 . Further, the results of flow cytometry demonstrated that p65 siRNA could induce apoptosis of SCL-1 cells, and cell apoptosis ratio (20.28% ± 1.87%) in p65 siRNA group was significantly higher than that in the untreated group and control siRNA group (9.13% ± 1.51% and 9.37% ± 1.38%, respectively, F=47.532, P<0.01)., Conclusion: p65 siRNA can block NF-kappaB signal pathway, down-regulate expression of bcl-2, elevate the bax level and increase the activities of caspase-3/9, suggesting that NF-kappaB signal pathway may be a key molecular target for therapy of cutaneous SCC.