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Pyroptosis is a newly discovered programmed cell death in recent years.The researches show that pyroptosis plays an important role in many diseases.Leukemia is a malignant hematopoietic stem cell disease, which seriously threatens the health and life of children.Numerous studies have shown that pyroptosis is associated with the occurrence and development of leukemia, and elucidation the mechanism of pyroptosis in leukemia will provide a new method of clinical treatment.In this review, in order to enhance the understanding of the mechanism of pyroptosis and provide some ideas for the treatment of leukemia, the molecular mechanism of pyroptosis and its role in leukemia are reviewed.
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Objective:To evaluate systematically the association between the c. 415>C polymorphism of NUDT15 gene and the toxicity of 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL).Methods:The literatures in domestic and foreign databases were retrieved: PubMed, EmBase, Cochrane Library, CNKI, CBM, VIP Chinese Sci-tech Journal Database, and Wanfang Database.The language was limited to Chinese or English.A case-control study or cohort study of 6-MP treatment in pediatric ALL related to the toxicity of the NUDT15 gene c. 415>C polymorphism was included.The time of search was set from the establishment of the database to October 1st, 2020.Two researchers screened the literature independently, extracted data from the literature that met the inclusion criteria, and evaluated the quality of the included studies.The association between locus polymorphism and toxicity during 6-MP chemotherapy was analyzed by Meta analysis with Rev Man 5.3 and Stata 12.0 software.Results:Nine studies were finally included, eight of which were cohort studies and one was a case-control study, with a total of 1 068 patients.The results showed that under the five genetic models, the mutation at c. 415>C of NUDT15 gene was significantly associated with the risk of leukopenia and neutropenia( P<0.01), while hepatotoxicity was with no significant association between the occurrence risk of damage( P>0.05). Conclusion:The mutation at c. 415>C of NUDT15 gene significantly increased the incidence of leukopenia and neutropenia during 6-MP chemotherapy, while there was no significant effect on the occurrence of hepatotoxicity.
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Objective To study the effect of MEK-ERK signaling pathway on diallyl disulfide (DADS)-induced autophagy in human leukemia K562 cells. Methods K562 cells were divided into experimental group, solvent group and blank control group. K562 cells in the experimental group were cultured with 10, 20, 40, 80 mg/L DADS for 48 h. The morphological changes were observed by inverted microscope, monodansyl cadaverine (MDC) staining was used for detecting the formation of the autophagic vacuoles (AV), and the rates of autophagy were analyzed by flow cytometry. Western blot was used to determine the level of expression of ERK, phospho-ERK (p-ERK), LC3-Ⅱ. Results With the increasing of DADS concentration, the number of K562 cells was decreased significantly, and the morphology of some K562 cells became irregular and membrane deformed.The staining of cells and the number of green spots in the cells increased, suggesting that autophagy of the K562 cells cultured with DADS increased. The autophagy rates of K562 cells increased gradually after cultured with DADS for 48 h, the autophagy rate in 40 mg/L DADS group was the highest, and the autophagy rates in 20, 40 and 80 mg/L DADS group were higher than that in the blank control group (P<0.05). There were no significant difference in the expression level of ERK protein between each group (P> 0.05), with the increasing of DADS concentration, the protein expression of p-ERK and LC3-Ⅱ increased, there was significant difference in the protein expression of 40 mg/L DADS group (P<0.05). Conclusion DADS may induce autophagy of K562 cells by activating MEK-ERK signaling pathway through up-regulation of ERK phosphorylation.
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Objective To investigate the adjustment of miRNA-155 on CD4+ CD25+ Treg regulative T cell in peripheral blood in patients with acute cerebral infarction (ACI) and its pathogenesis. Methods Sixty patients with ACI were divided into three groups according to clinical neurological deficit score. Twenty healthy volunteers were enrolled into the control group. The expression levels of plasma miR-155 mRNA and Foxp3 mRNA were detected by real-time quantitative PCR(qRT-PCR). IL-10 levels in plasma were detected by ELISA. Results Expression of miR-155, Treg, Foxp3 mRNA and levels of IL-10 were significantly increased in patients with ACI compared with normal control group, with statistical differences; Expression of miR-155, Treg, Foxp3 mRNA and levels of IL-10 were gradually increased. The values showed significant statistical difference among the mild, moderate and severe ACI groups (P < 0.01). Among the patients,the levels of miR-155, Treg, Foxp3 mRNA and levels of IL-10 in the survival group were obviously lower than those in the non (P<0.05 or P<0.01). There was a positive correlation between miR-155 and Treg, Foxp3 mRNA (P < 0.01). Conclusion This study suggests that miR-155 is involved in the cell proliferation regulation of CD4+ CD25+ Treg cells,and plays some role in the immunological dissonance with ACI.
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Objective To investigate the effect of microRNA(miR)-21 on proliferation and differentiation of murine pulmonary fibroblasts. Methods C57BL/6 mice of SPF grade (n=24) were randomly divided into Sham group and Pulmo?nary fibrosis model group with 12 mice in each group. Pulmonary fibrosis model was established by trans-tracheal jet ventila?tion of bleomycin into mice. The transcription levels of miR-21 were examined by quantitative real-time PCR in various pul?monary fibrosis tissues. Primary fibroblast were isolated and digested by Trypsin then inoculated into 6 well plate to reach confluence of 30%-50%. PBS (2.5μL), negative control stock solution and miR-21 mimic stock solution (20μmol/L) were added into Opti-MEM (50μL) as control group, blank group and miR-21 mimic group respectively.The cell viability was as?sessed by CCK-8. Expressions of ADAMTS-1 and TGF-β1 in the pulmonary fibroblasts were tested using Western blot. Re?sults The expression of miR-21 was significantly increased in lungs of mice in pulmonary fibrosis model group than that in sham group. Expression of miR-21 was higher in miR-21 mimic group than that in control group and blank group. Expres?sion of miR-21 was significantly higher with better cell viability in miR-21 mimic group than that in control group and blank group. The expression of ADAMTS-1 was significantly decreased in miR-21mimic group, while the expression of TGF-β1, a target gene of miR-21, was significantly increased in miR-21 mimic group compared with the other two groups. There is no significant different in expressions of ADAMTS-1 and TGF-β1 between control group and blank group. Conclusion Over?expression of miR-21 in pulmonary fibroblasts disrupts TGF-β1 signaling pathway by reducing expression of ADAMTS-1, which promotes the proliferation and differentiation of pulmonary fibroblast.
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BACKGROUND:Astragaloside Ⅳ is a major component of Huangqi,promoting proliferation and differentiation of bone marrow mesenchymal stem cells;however,the mechanism has been less reported yet.OBJECTIVE:To explore the effect of Astragaloside Ⅳ on expression of multiple hematopoietic growth factors in bone marrow mesenchymal stem cells.METHODS:Bone marrow mesenchymal stem cells were isolated from adult Wistar rats by using the method of adhesive culture and clone,and they were then plated on 96-well plate and separately incubated with 100 uL Astragaloside Ⅳ(25,50,100,200 g/L)for 72 hours.The cells in the control group were cultured with an equal volume of DMEM-LG culture liuquid.Indirect immunofluorescence was used to detect the biological activity,MTT method was used to evaluate the effect of Astragaloside Ⅳ on proliferation and differentiation of bone marrow mesenchymal stem cells,and RT-PCR method was used to measure the expression of hematopoietic growth factors in bone marrow mesenchymal stem cells.RESULTS AND CONCLUSION:The 3~(rd)-passage bone marrow mesenchymal stem cells highly expressed CD44 but lowly expressed CD45.As compared with control group,Astragaloside Ⅳ promoted proliferation of bone marrow mesenchymal stem cells in a time/dosage-dependent manner,in particular,the 200 g/L Astragaloside IV and 72-hour intervention(P＜ 0.05).SCF expression was significantly increased in the drug group compared with control group(P ＜ 0.01);however,TPO,GM-CSF,and TGF-β1 expressions were not changed significantly(P ＞ 0.05).Moreover,interleukin-3 expression was not found in the bone marrow mesenchymal stem cells.Astragaloside Ⅳ promoted in vitro proliferation of bone marrow mesenchymal stem cells,possibly involving in SCF secretion.