Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats.

OBJECTIVE: To investigate the expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer (DFU) and its effect on angiogenesis in DFU rats. METHODS: The serum levels of miR-217, HIF-1α and VEGF were detected in DFU and simple diabetes mellitus (DM) patients, and healthy controls. DFU rat models were established and treated with miR-217 inhibitors and/or HIF-1α siRNA. The ulcer healing of DFU rats was observed. Besides, ELISA method was performed to detect the serum level of HIF-1α, VEGF and inflammatory factors, immunohistochemical (IHC) method to test the micro-vessel density (MVD), as well as qRT-PCR and Western blot to determine expressions of miR-217, HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 in tissues. RESULTS: The serum levels of miR-217 were up-regulated while HIF-1α and VEGF were down-regulated in DFU patients and rats when compared with DM and healthy controls (all P < 0.05). Dual-luciferase reporter gene assay confirmed that HIF-1α was the direct target gene of miR-217. DFU rats treated with miR-217 inhibitors had decreased foot ulcer area and accelerated ulcer healing, with significantly reduced inflammatory factors (IL-1ß, TNF-α and IL-6), as well as elevated HIF-1α and VEGF (all P < 0.05); meanwhile, they remarkably increased the MVD in foot dorsum wound tissues and the protein expressions of HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 (all P < 0.05). CONCLUSION: Inhibiting miR-217 could up-regulate HIF-1α/VEGF pathway to promote angiogenesis and ameliorate inflammation of DFU rats, thereby effectively advancing the healing of ulcerated area.

[Steroid contraceptives causing no increase in risk of thromboembolism (case-control study)].

PIP: In order to obtain information on the safety of steroids in oral contraceptive I made in China, a case-control study was cond ucted in Shanghai. 62 first-time female patients aged 15-59 who were hospitalized or seen at the emergency room between February 1989 and January 1990 in 7 collaborating hospitals, and who were diagnosed with AMI, cerebral embolism, and thrombosis were studied in comparison with a control group of 181 women. The controls were nonthromboembolism patients at the same age who were hospitalized in the same hospital and at the same time. All women were interviewed about their pregnancies and birth histories, use of steroid contraceptives, and other medicines as well as about diseases and family histories, among other things. Information was also taken from their hospital records. Logistic regression was conducted for single- and multivariate analysis using SPSS/PC+ and Epic software packages. 21% of the cases and the controls used some kind of steroid contraceptives in the past. 92% of the cases had cerebral embolism and were age 30 or over. The result of the analysis showed that the use of steroid contraceptives was not associated with the increased risk of thromboembolism. The important factors associated with thromboembolism were high blood pressure. The duration of the use of steroid contraceptives and the time span from the termination of the use of steroid contraceptives to the occurrence of thromboembolism was not associated with the increase risks of the disease. The authors believed that the findings of the study reflected that fact that none of the cases and the controls smoke or drink. And the most commonly used steroid contraceptives were low dose Oral Pill I suggesting it is a safe method of contraception.^ieng