Methylophiopogonanone A suppresses ischemia/reperfusion-induced myocardial apoptosis in mice via activating PI3K/Akt/eNOS signaling pathway.

AIM: The dried tuber root of Ophiopogon japonicus has been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid in Ophiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury. METHODS: Mice were pretreated with MO-A (10 mg·kg(-1)·d(-1), po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. RESULTS: In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 µmol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L). CONCLUSION: MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.

[Expression and clinical significance of IL-17 and IL-21 in patients with acute leukemia].

This study was aimed to investigate the effects of peripheral blood Th17 cells, IL-17 and IL-21 in the occurrence and development of acute leukemia. 60 patients with acute leukemia (19 patients with ALL, 41 patients with AML) were divided into non-remission group (group A, n=24), remission group (group B, n=36); 25 healthy volunteers were used as control group (group C). In addition to this, these 60 patients were divided into infection group (n=32) and non-infection group (n=28) on the basis of infection status. The concentration of IL-17 and IL-21 in the peripheral blood mononuclear cell culture supernatant after stimulation with anti-CD3 and anti-CD28 mAb were determined with ELISA. The expression of CD4+ IL-17+ cells was determined by flow cytometry. The results showed that (1) the concentrations of IL-17 and IL-21, and proportion of Th17 cells in group A and group B were much lower than those in group C (p<0.05); (2) the expression levels of IL-17 and IL-21, and the proportion of Th17 cells in group A were lower than those in group B (p<0.05); (3) the expression levels of Th17 and IL-17 in infection group were lower than those in non-infection group (p<0.05). It is concluded that Th17 cells may play important roles in the occurrence and development of acute leukemia through secreting IL-17 and IL-21, and their functional level can partially reflect the status of leukemia and can be used to evaluate the risks of infection in patients with leukemia.

[Studies of the association between angiotensinogen gene regulation and cytokines in essential hypertension].

This study is to explore the association between M235T allele polymorphism of angiotensinogen (AGT) gene and cytokines using essential hypertension probands research method. In hypertensives and controls, polymerase chain reaction combined with restriction endonuclease digestion was used to detect the target genotype variation, and enzyme-lined immunosorbant assay (ELISA) was used to detect the cytokine concentrations (IL-1, IL-6, TNF). The results showed that in hypertensives AGT gene, TT genotype was 55.88%, MT 35.29% and MM 8.82%. The ratio of T/M allele frequency was 0.735/0.265. In controls AGT gene, TT genotype was 47.46%, MT 42.37% and MM 10.17%. The ratio of T/M allele frequency was 0.686/0.314. AGT gene 235 T allele frequency in hypertensives was slightly higher than those in controls. Furthermore AGT gene 235 TT genotype and T allele frequency in middle and high grade of hypertensives were significantly higher than those in mild grade. In subjects of AGT 235 T allele group, the concentrations of IL-1, IL-6 and TNF in hypertensives were significantly higher than those in controls. In subjects of AGT gene 235 M allele frequency, the concentrations of IL-1 and IL-6 in hypertensives were no significant than those in controls. No matter in groups more than 60 years old or less than 60 years old, the concentrations of IL-1, IL-6 and TNF in hypertensives were higher than those in controls. No matter in hypertensives or controls, there were no differences in concentrations of IL-1, IL-6 and TNF when comparing groups more than 60 years old with groups less than 60 years old. The study indicated that AGT gene TT genotype and AGT gene 235 T allele frequency may be an important risk factor for hypertension. The high frequency of AGT gene 235 T allele and the high concentrations of IL-1, IL-6 and TNF in hypertensives may cause hypertension developing. It is also suggested the cytokines may effect the transcription and expression of AGT gene 235 TT genotype in hypertension. The concentrations of IL-1, IL-6 and TNF had nothing to do with age no matter hypertensives or controls.