Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis.

BACKGROUND: The roots of Salvia miltiorrhiza are used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient of Salvia miltiorrhiza which can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear. METHODS: CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell apoptosis. RESULTS: Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p. We subsequently identified that AKT3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells. CONCLUSIONS: Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway.

Comparison of a multiple daily insulin injection regimen (glargine or detemir once daily plus prandial insulin aspart) and continuous subcutaneous insulin infusion (aspart) in short-term intensive insulin therapy for poorly controlled type 2 diabetes patients.

Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes.

AIM: To evaluate the correlation between nonalcoholic fatty liver disease (NAFLD) and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from 1217 inpatients with T2DM (757 females, 460 males; aged 63.39 ± 12.28 years). NAFLD was diagnosed by hepatic ultrasonography. Diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) were diagnosed according to their respective criteria. The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression, respectively. RESULTS: Approximately 61% of inpatients with T2DM in Qingdao, China had NAFLD, which decreased significantly with increase in age and prolonged course of diabetes. The prevalence of NAFLD in patients presenting with DN, DPN and DR was 49.4%, 57.2% and 54.9%, respectively. These rates were significantly lower than those of patients without DN, DPN and DR (65.9%, 65.6% and 66.1%, respectively, P < 0.05). Participants with NAFLD had greater body weight, waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, blood pressure, as well as triglyceride (TG) levels and lower high-density lipoprotein (HDL) concentration than those without NAFLD (P < 0.05). NAFLD was positively correlated with BMI, WC, TG, FBG, diastolic blood pressure, and systolic blood pressure but negatively correlated with the duration of diabetes, DR, DPN, DN, and HDL. CONCLUSION: Despite the benign nature of NAFLD, efforts should be directed toward early diagnosis, intensive blood glucose and blood pressure control, and effective dyslipidemia correction.