ABSTRACT
Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare,critical and complicated cyanotic congenital heart disease,the natural mortality rate is high,if not treated,50％ of newborns died within 2 weeks after birth,about 85％ of newborns will die within six months.In recent years,with cardiac surgery procedures,catheter intervention and other treatment levels improved,the survival rate of newborns after surgery has improved.Over the past decade,the disease 5-year survival rate increased by 75％ or more.In this paper,PA/IVS cardiac surgery procedures,catheter intervention and hybrid treatment were reviewed,aimed at providing a reference for clinical treatment.
ABSTRACT
Objective:To explore the effect of taxifolin on H2O2-induced pyroptosis in H9C2 cells and the possible mechanisms.Methods:The H9C2 cells was divided into 3 groups:a control group,a hydrogen peroxide (H2O2) group and a taxifolin group.The morphology of H9C2 cells was observed by inverted phase contrast microscope.The mitochondrial membrane potential was measured by JC-1 staining and flow cytometry.The alteration of the level of reactive oxygen species (ROS) was detected by specific mitochondrial probe.The protein levels of cysteinyl aspartate specific proteinase-1 (caspase-1) was determined by Western blot.The mRNA levels of interleukin-18 (IL-18),interleukin-1a (IL-1a),interleukin-1b (IL-1b),absent in melanoma 2 (AIM2),apoptosis-associated apeck-like protein (ASC),nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)and nucleotide-binding oligomerization domain-like receptor family caspase recruitment domaincontaining protein 4 (NLRC4) were determined by reverse transcription-polymerase chain reaction (RT-PCR).Results:Compared with the control group,the morphology of H9C2 cells obviously changed in the H2O2-treated group,which was guadually improved in the presence of taxifolin.Compared with the control group,the mitochondrial membrane potential was markedly decreased in the H2O2-treated cells,accompanied by the increase of ROS (both P＜0.05).Compared with the H2O2 group,the mitochondrial membrane potential changes in the taxifolin group was increased while the ROS was decreased,with significant difference (both P＜0.05).Compared with the control group,the protein level of caspase-1 and the mRNA levels of IL-18,IL-1a,IL-1b,AIM2,ASC,NLRP3 and NLRC4 in the H2O2-treated group were significantly increased (all P＜0.05),which were attenuated in the presence of taxifolin (all P＜0.05).Conclusion:Taxifolin can protect H9C2 cells from oxidative injury,and it is able to suppress the H2O2-induced H9C2 cell pyroptosis through inhibition of AIM2,NLRP3 and NLRC4 in flammasome.
ABSTRACT
To observe the effect of high-mobility group box 1 (HMGB1) on autophagy and chemotherapy resistance in human leukemiacell line (K562) cells, and to explore the underlying mechanisms. Methods: The K562 cells were cultured in vitro and divided into 6 groups: a chemotherapeutic group, a chemotherapeutic control group, a HMGB1 preconditioning group, a HMGB1 preconditioning control group, a HMGB1 siRNA group and a siRNA control group. The chemotherapeutic group was further divided into a vincristine (VCR) group, an etoposide (VP-16) group, a cytosine arabinoside (Ara-C) group, a adriamycin (ADM) group and a arsenic trioxide (As2O3) group. The cell activity was evaluated by cell counting kit-8. The protein levels of HMGB1, microtubule-associate protein1light chain3 (LC3), AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) were determined by Western blotting. The level of serum HMGB1 was evaluated by enzyme-linked immunosorbent assay (ELISA). The autophagy was examined by monodansylcadaverine staining and observed under transmission electron microscopy. Results: Compared with the control group, the cell activity was significantly decreased and the level of serum HMGB1 was significantly increased in the chemotherapeutic (VCR, VP-16, Ara-C, ADM and As2O3) groups (all P<0.05). Compared with the control group, the cell activity and the level of serum HMGB1 were significantly increased in the HMGB1 preconditioning group (both P<0.05). Compared with the siRNA control group, the cell activity and the level of serum HMGB1 were significantly decreased in the HMGB1 siRNA group (both P<0.05). Compared with the control group, the expression of LC3-II and the formation of autophagic bodies were increased in the HMGB1 preconditioning group (both P<0.05), the p-AMPK expression was increased and p-mTOR expression was decreased (both P<0.05). Conclusion: HMGB1 can increase the autophagy and promote chemotherapy resistance through the pathway of AMPK/m-TOR in K562 cells.