Harringtonine induces apoptosis in NB4 cells through down-regulation of Mcl-1 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the growth inhibition effect, cytotoxicity and apoptotic induction of harringtonine (HT) in human acute promyelocytic leukemia (APL) NB4 cells,and the related mechanism.</p><p><b>METHODS</b>NB4 cells were treated with HT. Total cell numbers were counted by hemocytometer, and cell viabilities were determined by trypan blue exclusion. Apoptotic cells were determined by fluorescence microscopy and FACS after staining with AO and EB or PI, respectively. The cleavage of PARP and the activation of Bax and the expression of anti-apoptotic proteins were determined by Western Blot. siRNA was used to silence the expression of target genes. Primary cells were isolated following Ficoll-Hypaque density gradient centrifugation method.</p><p><b>RESULTS</b>HT inhibited cell growth and induced apoptosis of NB4 cells in a dose- and time-dependent manner. Apoptosis induced by HT was correlated with the down-regulation of Mcl-1 and the cleavage of PARP, while HT did not affect the protein level of Bax and Bak or change the protein level of Bcl-2. The silence of Bcl-XL sensitized HT-induced apoptosis in NB4 cells.Apoptosis induced by HT in primarily cultured APL cells was also correlated with the down-regulation of Mcl-1.</p><p><b>CONCLUSION</b>HT inhibits cell growth and induces apoptosis in NB4 cells and primarily cultured APL cells, which may be associated with down-regulation of Mcl-1.</p>

The Dynamic Change of GPI-80 in Childhood Anaphylactoid Purpura / 中华皮肤科杂志

Objective To analyze the relationship between dynamic change of GPI-80 and disease severity and prognosis of childhood anaphylactoid purpura. Methods Patients were collected and divided into three groups according to their clinical features: purpura group (purpura only), mixed group (purpura + arthritis + gastrointestinal bleeding) and nephritis group. There were 20 patients in each group. GPI-80 expression on the neutrophils was detected by flow cytometry during acute and regressive phases of the disease. GPI-80 expression was compared among different groups and different phases. Renal biopsies were performed in 20 nephritis patients. Results GPI-80 expression was significantly increased in all patient groups compared with that in the normal control (P 0.05). No significant difference of GPI-80 expression was found among 20 nephritis patients with different pathological patterns. Forty-two patients (10 in purpura group, 15 in mixed group, and 17 in nephritis groups) were followed up and GPI-80 expression was detected at the time of discharge and 2 weeks after discharge, the results showed that GPI-80 expression was decreased from 93.26% (?7.89%) at acute phase to 91.37% (?6.9%) at regressive phase with an average interval of 13.5 days. Most of them (35/42) further decreased to 38.44% (?7.8%) in 2 weeks after discharge. GPI-80 expression remained high in 7 patients for 2 weeks after discharge and relapsed in 5 patients within 1 month after discharge. Conclusions High GPI-80 expression is related to the severity of the disease. The decrease of GPI-80 takes place later than the improvement of clinical symptoms. Children with persistently high GPI-80 expression are likely to relapse. It seems that there is no correlation between GPI-80 expression and different pathological patterns of nephritis.