Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
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Question: Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.', 'The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.', 'There were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose-response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for 67 months for time since starting insulin, 39,000 units for cumulative dose of insulin, and 21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.

Answer: Does prolonged use of human insulin increase breast cancer risk in Taiwanese women with type 2 diabetes?

Question: Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF)-1 regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease.

Answer: Does exosomal transfer of miR-30a between cardiomyocytes regulate autophagy after hypoxia?

Question: Transplanted cell survival might greatly improve the therapeutic efficacy of cell therapy. Diazoxide (DZ), a highly selective mitochondrial ATP-sensitive potassium channel opener, is known to suppress cell apoptosis and protect cells in oxidative stressed ischemic environment. We explored the mechanisms involved in DZ pre-treatment-induced anti-apoptotic effect on L6 skeletal myoblast (SKM).', 'L6 SKMs were divided into control group, H2O2 group, DZ+H2O2 group and DZ+LY+H2O2 group. Treatments of 400mol/L H2O2 for 24h alone, or after 200mol/L DZ pre-treatment for 30min, or after DZ and 50mol/L LY294002 co-administration for 30min were performed. The cell apoptosis rates were assessed by flow cytometric analysis. The changes of mitochondrial membrane potential were determined by JC-1 mitochondrial staining. The activation of phosphatidylinositol-3 kinase (PI3K)/Akt, caspase-9 and caspase-3 was detected by western blot.', 'Compared with the H2O2 group, DZ pre-treatment protected cells from H2O2-induced damage, increased Akt phosphorylation, prevented mitochondrial membrane depolarization as well as the activation of caspase-9 and caspase-3 and decreased the cell apoptosis rate. However, the DZ-induced cytoprotective and anti-apoptosis effects were partly inhibited by co-administration of a PI3K inhibitor, LY294002.

Answer:
Does diazoxide protect L6 skeletal myoblasts from H2O2-induced apoptosis via the phosphatidylinositol-3 kinase/Akt pathway?