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Objective The inhibitory effect of the PARP inhibitor olaparib on human acute myeloid leukemia HL-60 cells was studied. Methods The HL-60 cells in logarithmic growth phase were treated with different concentrations(1. 25,2. 5,5 and 10 μmol/L) of olaparib for different time. The CCK-8 assay was used to detect the inhibitory effect of olaparib on HL-60 cells. The apoptotic level of HL-60 cells was detected by Annexin-V/PI double staining method,and the expression of related signal proteins ( PARP-1 and caspase-3)in HL-60 cells was detected by Western blot. Results HL-60 cells were inhibited by olaparib at dif-ferent concentrations(1. 25,2. 5,5 and 10 μmol/L) for 48 h,and the inhibition rate gradually increased with the prolongation of the action time;at the same time,the apoptotic rate was increased in HL-60 cells after olaparib treatment for 48 h,showing a dose-de-pendent manner;the PARP activity was inhibited and caspase-3 was activated in HL-60 cells treated with olaparib. Conclusion The PARP inhibitor olaparib not only inhibits proliferation of HL-60 cells,but it also promotes apoptosis of HL-60 cells by inhibi-ting PARP activity and activating caspase-3.
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an inflammatory lung injury induced by a variety of factors, and these diseases are associated with high rates of mortality due to the lack of effective treatments. Based on the latest research in ALI/ARDS, it is widely accepted that generalized inflammatory responses play a critical role in initiating and developing process of ALI/ARDS. We make a brief review on the immune-pathogenesis and the signaling pathways of ALI/ARDS from the perspective of inflammation, thereby helping develop novel therapeutic strategy for treatment of patients with ALI/ARDS.
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Objective To investigate the mechanism of matrine in inhibition of proliferation the proliferation of human chronic myeloid leukemia (CML) K562 cells via MEK-ERK signaling pathway. Methods Western blot was used to detect the expression of MEK1, ERK1/2, Shc and SHP2 (the signal effect molecules of MEK-ERK pathway) in K562 cells. The transcription and translation of bcr-abl and target protein (bcl-xL, Cyclin D1, c-myc and p27) were detected by RT-PCR and Western blot. Results Matrine was able to significantly inhibit the phosphorylation of MEK1, ERK1/2, Shc and SHP2 in K562 cells and suppress the protein and mRNA expression of bcr-abl. Moreover, the expressions of bcl-xL, Cyclin D1 and c-myc were down-regulated significantly, while the expression level of p27 (a negative regulator of cell cycle progression) was increased markedly after matrine treatment. Conclusions Suppression of the growth of human CML K562 cells is related to the inhibition of bcr-abl-mediated MEK-ERK pathway activity. The down-regulation of phosphorylated proteins or protein kinases activity in signaling pathways might be an important molecular mechanism in control the activity of MEK-ERK pathway.
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Paclitaxel is one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers.However,its clinical application has been limited due to its poor water solubility.Its current clinical administration results in serious side effects and has undesired pharmacokinetics and biodistribution.Therefore,it is need to develope alternate drug delivery systems of paclitaxel to enhance its solubility,permeability and stability,furthermore to promote a sustained,controlled and targeted delivery.Hyaluronic acid as the carrier of drug delivery system can solve the problems.Hyaluronic acid-paclitaxel nanoparticles have high anticancer efficiency in drug encapsulation and tumor cellular uptake,due to their appropriate size,surface modification and interaction with CD44.This review focuses on recent applications of hyaluronic acid-paclitaxel nanoparticles in a variety of malignant tumors.
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Objective To recover laboratory data and software function in machine-number-based encryption. Methods Database and cryptograph files were replaced respectively by the corresponding files backuped previously after the operating software of Tecan SunRise setting up in new system,and set essential configuration. Results Laboratory data and software function were recovered entirely,and apparatus ran normally. Conclusion Besides database files,the cryptograph files were also essential data, which must be preserved in machine number based encryption.