Inhibition of Combination of Icaritin and Doxorubicin on Human Osteosarcoma MG-63 Cells in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the inhibition and molecular mechanism of icaritin (ICT) combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro.</p><p><b>METHODS</b>The control group, ICT groups (10, 20, 40, 80, and 160 µmol/L), DOX groups (1, 2, 4, 8, and 16 µg/mL), and combination groups (20 µmol/ L ICT +1 µg/mL DOX, 20 µmol/L ICT +2 µg/mL DOX, 20 µmol/L ICT +4 µg/mL DOX, 40 µmol/L ICT +1 µg/mL DOX, 40 µmol/L ICT +2 µg/mL DOX, 40 µmol/L ICT +4 µg/mL DOX, 80 µmol/L ICT +1 µg/mL DOX, 80 µmol/L ICT +2 µg/mL DOX, 80 µmol/L ICT +4 µg/mL DOX) were set up. Human osteosarcoma MG-63 cells were respectively cultured and their effects on morphological changes were observed using inverted phase contrast microscope after 24-and 48-h intervention. The cell proliferation inhibition rate of each group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression levels of bcl-2, caspase-3, and p21 were detected using RT-PCR.</p><p><b>RESULTS</b>ICT and DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT concentration increasing from 10 µmol/L to 160 µmol/L, the cell proliferation inhibition rate also increased gradually from 9.67% ± 3.62% to 89.18% ± 9.66%. The IC50 was 46.93 µmol/L and 3.87 µg/mL respectively. ICT and DOX could cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression, and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05). Aforesaid changes were more obviously seen in combination groups than in lCT groups and DOX groups (P < 0.05).</p><p><b>CONCLUSION</b>CT combined DOX had additive or synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells, which might be related with regulating gene expressions of bcl-2, caspase-3, and p21.</p>

Clinical characteristics and antimicrobial resistance of invasive pneumococcal disease in children / 中华儿科杂志

<p><b>OBJECTIVE</b>Streptococcus pneumoniae (SP) is a major causative agent of community-acquired pneumonia. In children older than 2 months, SP is also the most common cause of invasive bacterial infections. Invasive pneumococcal diseases (IPD) have become a severe problem of public health worldwide. The aim of this study was to summarize the clinical characteristics and antimicrobial resistance of IPD in children, and to raise the level of diagnosis and treatment of this disease.</p><p><b>METHOD</b>The clinical data from 55 cases of IPD younger than 12 years old seen from January 2004 to June 2009 in Yuying Children's Hospital Affiliated to Wenzhou Medical College were analyzed retrospectively. Blood, cerebrospinal fluid (CSF), seroperitoneum, mediastinum and soft tissue aspirate specimens were collected from these children, and 64 SP strains were cultured, isolated and confirmed and the antibiotics susceptibility to penicillin and other antibiotics of these strains were assessed.</p><p><b>RESULT</b>The 55 cases of IPD were identified, among whom 32 were male and 23 female, the ratio was 1.39. The ages ranged from 47 days to 12 years. Most (62%) of the cases were aged less than 2 years, and 16% were aged from 2 to 5 years. Overall, 38 (69%) had septicemia, of whom 8 cases were complicated with meningitis, 2 with pneumonia complicated with empyema, 1 had pneumonia complicated with mediastinal abscess and 11 with pneumonia. Nine cases (16%) were diagnosed as meningitis. Seven cases (13%) had hip or neck abscess and 1 case had purulent peritonitis. Thirteen cases (24%) had an underlying disease, including mainly leukemia (31%), followed by congenital heart disease (23%) and head trauma (15%). Three cases (5%) had received a surgical operation; 3 cases (5%) had combined virus infections and 2 cases (4%) had mycoplasma infection. Most (73%) episodes occurred in winter and spring. The main origin of infection was community (89%). Forty of the patients were cured, 12 improved and 3 died (5%). Nine cases (16%) developed neurologic complications. There was a statistically significant differences in the annual detection rate of invasive SP (chi(2) = 33.93, P < 0.01). The incidence of penicillin-intermediate S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 30% and 41%, respectively; the resistance to erythromycin and lincomycin were found in as high as 94% and 88% of isolates, respectively; while the resistant rate to chloramphenicol and cefotaxime were low, 26% and 22%, respectively. The multidrug resistance rate was 89%.</p><p><b>CONCLUSION</b>Children aged less than 5 years, especially younger than 2 years are prone to IPD and the underlying diseases are found in 24% of cases; septicemia and meningitis are the common diseases.</p>

Crosstalk between ERK1/2 and STAT3 in the modulation of cardiomyocyte hypertrophy induced by cardiotrophin-1 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway are the two major independent signal transduction pathways. However, it has recently been found that STAT3 may be negatively regulated by ERK1/2 in gp130-dependent signaling. Cardiotrophin-1 (CT-1), a potent novel hypertrophic cytokine, depends on gp130 to induce signaling and depends on STAT3 to exert hypertrophic effect. In this study, we examined whether STAT3 activity was negatively regulated by ERK1/2 during CT-1-induced signaling in rat cardiomyocytes and, if so, whether such crosstalk interfered with the hypertrophic effect of CT-1 and, furthermore, whether the mechanism underlying the crosstalk involved phosphorylation of serine 727 (S727) in STAT3.</p><p><b>METHODS</b>The activities of ERK1/2 and STAT3 were assessed by in-gel kinase assay and Western blot analysis, respectively. The role of S727 phosphorylation in the crosstalk between ERK1/2 and STAT3 was determined by a transient transfection study using a STAT3S727A mutant. Cardiomyocyte hypertrophy was evaluated by the cellular protein-to-DNA ratio and [(3)H]-leucine incorporation.</p><p><b>RESULTS</b>CT-1 simultaneously activated both ERK1/2 and STAT3 in rat cardiomyocytes. Inhibition of ERK1/2 by U0126 resulted in an increase of CT-1-induced tyrosine phosphorylation of STAT3 and, consequently, the protein-to-DNA ratio and [(3)H]-leucine incorporation. Transient transfection of the cells with STAT3S727A had no significant effect on CT-1-induced tyrosine phosphorylation of STAT3.</p><p><b>CONCLUSIONS</b>STAT3 is activated by CT-1 in rat cardiomyocytes, but full activation is mitigated by the simultaneous activation of ERK1/2. The inhibition of ERK1/2 increases the activity of STAT3, which, in turn, enhances the hypertrophic effect of CT-1. The crosstalk between ERK1/2 and STAT3 is independent of the phosphorylation of the S727 in STAT3. Such crosstalk may contribute to the development of adequate cardiac hypertrophy.</p>