Role of PI3K/Akt Pathway in MMC Induced Apoptosis of Liver Stem Cells / 华中科技大学学报(医学版)

Objective To investigate the role of PI3K/Akt pathway in mitomycin(MMC) induced apoptosis of liver stem cells.Methods Rat liver stem ceils were stimulated with MMC,and the effect of MMC on the apoptosis rate of WB-F334 cells at different time points(6,12,24 h),as well as the effects of different concentrations of (0.2,0.4,0.6,0.8,1.0 mg/mL) MMC on the cytotoxicity of WB-F334 cells were evaluated;moreover,cells were treated with p38 MAPK inhibitor and PI3K/Akt inhibitor,and the roles of MAPK and PI3K/Akt signaling pathway in MMC mediated apoptosis of WB-F334 cells were explored.Results The apoptosis rate of the MMC-treated WB-F334 increased with time(P＜0.05).Compared with the un-treated control group,different concentrations of MMC had obvious cytotoxicity on liver stem cells,and the cytotoxicity increased with concentration.Western blotting results showed that Akt and MAPK in WB-F334 cells were significantly phosphorylated 15 min after MMC stimulation;the degree of phosphorylation decreased with time,and phosphorylation disappeared after 60 min,suggesting that the p38 MAPK,PI3K/Akt pathway can be activated by MMC;furthermore,when p38 MAPK inhibitor was added to MMC treated cells,the apoptosis rate of p38 MAPK inhibitor treated cells showed no significant difference compared to the un-treated cells(P＞0.05),indicating that the MAPK pathway had no significant effect on MMC induced WP,-F334 cell death;however,when the PI3K/Akt inhibitor(API-2)was added,the apoptosis rate of API-2 treated cells was significantlv decreased compared to the un-treated cells(P＜0.05),indicating that the PI3K/Akt pathway had a significant effect on MMC induced apoptosis of WB-F334 cells(P＜0.05).Conclusion Stimulation of MMC can induce apoptosis of hepatic stem cells WB-F334 through the activation of the PI3K/Akt signaling pathway.

Study on chemical constituents of Lycopodium alkaloids / 中国中药杂志

<p><b>OBJECTIVE</b>To study the alkaloid chemical constituents of Lycopodium japonicum.</p><p><b>METHOD</b>Compounds were isolated and purified by such methods as silica gel column chromatography, RP-C18 reversed phase column chromatography, Sephadex LH-20 column chromatography and Waters semi-preparative liquid chromatogram, and their structures were identified based on physicochemical property and spectrum data.</p><p><b>RESULT</b>Nine known alkaloid chemical constituents were isolated and identified, they were lycodoline (1), lucidioline (2), alpha-obscurine (3), lycopodine (4), lycoposerramine-L (5), lycoposerramine-M (6), 11alpha-O-acetyl-lycopodine (7), des-N-methyl-a-obscurine (8), clavolonine (9).</p><p><b>CONCLUSION</b>Compounds 4-9 were obtained from L. japonicum for the first time.</p>

Selection and anti-cancer effects of siRNAs targeting Hmga2 gene / 药学学报

High mobility group A2 protein (HMGA2), an architectural factor, is highly expressed in various cancer types including lung cancers. It is a candidate target for cancer therapy. RNAi is an effective gene silencing method with low cost and less time-consuming. It is possible to exploit this technology in therapy. Here, 5 siRNAs targeting Hmga2 gene (HMGA2 siRNA1-5) were designed and synthesized. MTT assay, colony formation assay, transwell assay and flow cytometry were used to evaluate the effects of these siRNAs on lung cancer cell lines (NCI-H446 and A549). Results from cell proliferation, clone formation, migration and apoptosis showed that HMGA2 siRNA1, 3, 5 could affect these aspects for both lung cancer cell lines. Among the five siRNAs, HMGA2 siRNA5 showed the greatest inhibition effects. The inhibition effects of HMGA2 siRNA5 are sequence specific and are not due to the induction of interferon response. Taken together, siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene therapy.

Clinical significance of detecting minimal residual disease in acute leukemia / 白血病·淋巴瘤

Objective To investigate the clinical significance of flow cytometry (FCM) assay in following up of the minimal residual disease (MRD) used for predicting relapse and guiding chemotherapy. Methods The clinical data of 43 acute leukemia patients diagnosed by MIC were collected in our hospital from 2005 July to 2008 June.Bone marrow aspirates were collected from 43 patients with newly diagnosed acute leukemia after induction therapy and during constimulation therapy. The cells with leukemia associated with immunophenotype were investigated using FCM, as immunologic target of MRD. Results MRD were detected earlier in predicting the relapse than those of the traditional bone marrow cells morphology assay by an average of 4-6 months. The results of the MRD following up: MRD was negative at CR in 26 cases, 6 cases relapse, 20 cases of them were kept negative during following up. MRD was positive in 17 cases at CR, 9 cases of them were relapse. 4 cases after intensified chemotherapy the MRD became negative and kept egative for more than one year. The MRD of the 43 cases at CR were divided into 3 groups, MRD less than 1×10-4 group (A group) MRD between 5×10-3 and 1×10-4 group (B group) and MRD above 5×10-3 group(C group). By chi square test. There was no statistical significance between A group and B group, but there was tatistical significance between B group and C group (P=0.02). Conclusion The application of FCM in detecting MRD has important clinical significance in predicting relapse and guiding chemotherapy.

Identification and Analysis of Organic Pollutants in Child-Bearing Age Women Body / 环境与健康杂志

Objective To investigate the exposure levels of organic pollutants in child-bearing age women body. Methods The blood and urine specimens were collected simultaneously from each of 8 health women, aged 23-32 years, the organics were extracted with hexane and determined qualitatively by gas chromatography-mass spectrometer (GC-MS) for each specimen. Results In blood, 34 kinds of organic compounds had been detected , at average of (8.63?5.01 )kinds per person. Di-n-butyl phthalate (100%) and 14-bate-H-pregna (75.0%) revealed the highest detectable rates. In urine, 39 kinds of organic compounds had been identified, at average of (10.63?1.30) kinds per person, di-n-butyl phthalate(100%), HANFETT(100%), 14-bate-H-pregna(87.5%), docosane (87.5%), di-isobutyl phthalate(75.0%) were the chemicals noticed more frequently. Some kinds of these identified organics compounds were environmental toxic pollutants. Conclusion This study suggested that toxic organic pollutants had existed in child-bearing age women body, phthalic acid esters were the chemicals checked out more frequently. Their potential adverse health effects on women and offspring should be paid highly attention to.

Advances in Reproductive and Developmental Toxicity of Dibutyl Phthalate / 环境与健康杂志

Dibutyl phthalate (DBP) has been found as a ubiquitous environmental pollutant with reproductive and developmental toxicity. The characteristics of reproductive and developmental toxicity of DBP, the mechanisms of the toxicity and effects on human health were reviewed in this paper according to the toxic effects on pregnant animals exposed to DBP, which might provide reference for the further study on toxicity of DBP and preventive measures.