Effects of artesunate combined with bortezomib on apoptosis and autophagy of acute myeloid leukemia cells in vitro and its mechanism / 中华血液学杂志

Objective: To investigate the effects of artesunate combined with bortezomib on the proliferation, apoptosis and autophagy of human acute myeloid leukemia cell lines MV4-11, and its mechanisms. Methods: MTT method was used to determine the anti-proliferation effect of different concentrations of artesunate, bortezomib and their combination on MV4-11 cells. The cell apoptosis were analyzed by flow cytometry. The expression of cleaved-Caspase-3, Bcl-2 family protein (Bcl-2, Mcl-1, Bim, Bax) and autophagy-related protein LC3B were assayed by Western blot. Results: Artesunate displayed a proliferation inhibition effect on MV4-11 with dose- and time-dependent manner, the IC(50) of artesunate on MV4-11 after 48 hours was 1.44 μg/ml. Bortezomib displayed a proliferation inhibition effect on MV4-11 with dose-dependent manner, the IC(50) of bortezomib on MV4-11 after 48 hours was 8.97 nmol/L. The combination of artesunate (0.75, 1.0 μg/ml) and Bortezomib (6, 8 nmol/L) showed higher inhibition on MV4-11 than artesunate or bortezomib alone in the same concentration gradient after 48 hours (P<0.05) . The cooperation index of the two drugs were all less than 1. The 48 h apoptotic rate of artesunate (1.5 μg/ml) on MV4-11 was (15.27±2.18) %, (19.85±3.23) % of bortezomib (8 nmol/L) , (81.67±5.96) % of combination of the two drugs, significantly higher than the single group (P<0.05) . When combination of the two drugs on MV4-11 after 24 hours, the levels of pro-apoptotic protein Bim and the cleaved activation of Caspase-3 and autophagy-related protein LC3B were up-regulated and the anti-apoptotic protein Bcl-2 expressions was down-regulated. Conclusion: Combination of artesunate with bortezomib shows a significant synergistic effects on proliferation, apoptosis and autophagy of MV4-11 cell lines, which may be associated with Bcl-2 family proteins expression.

Perindopril, amlodipine and telmisartan improve arterial stiffness in patients with hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of perindopril, amlodipine and telmisartan on improving the artery stiffness in patients with hypertension.</p><p><b>METHODS</b>Patients with primary hypertension were randomly assigned to perindopril (4 mg/day), Amlodipine (5 mg/day) and telmisartan (80 mg/day) regimen for 3 months (n = 34 each). Brachial-ankle pulse wave velocity (baPWV) was measured by an automatic brachial ankle pulse wave velocity device before the treatment, one-month and three-month after the treatment.</p><p><b>RESULTS</b>(1) SBP, DBP and PP were significantly decreased in all three groups (P < 0.001). There were no significant changes in HR in all three groups (P > 0.05). (2) BaPWV was significantly decreased in all three groups. In the perindopril, Amlodipine, telmisartan group, baPWV was (1859 +/- 492) cm/s, (1780 +/- 335) cm/s, (1859 +/- 337) cm/s before the treatment; was (1757 +/- 508) cm/s, (1647 +/- 285) cm/s, (1632 +/- 261) cm/s one-month after the treatment; was (1702 +/- 538) cm/s, (1559 +/- 288) cm/s, (1566 +/- 326) cm/s three-month after the treatment. Compare the baPWV one-month after the treatment to before the treatment P < 0.001; Compare the baPWV three-month after the treatment to before the treatment P < 0.001; Compare the baPWV three-month to one-month after the treatment perindopril group and telmisartan group P < 0.01, amlodipine group P < 0.001. (3) The changes of baPWV in one or three months were significantly more in the telmisartan group than in the perindopril and amlodipine groups (1 months P < 0.01, 3 months P < 0.05). The change of baPWV was significantly greater in three months than in one montin in all three grops (P < 0.01).</p><p><b>CONCLUSION</b>Arterial stiffness of hypertensive patients was improved post Telmisartan, amlodipine and perindopril therapy in proportion to therapy duration. Telmisartan is superior to amlodipine and perindopril on improving arterial stiffness of hypertensive patients. Continuous anti-hypertensive treatment with telmisartan, amlodipine and perindopril will have a persistent improvement of the artery flexibility.</p>