Panminerva medica最新文献

Background: The aim of this study was to investigate the effect of Farnesoid X receptor (FXR) on oxidative stress injury of H9C2 cardiomyocytes induced by endothelin-1 (ET-1), and to explore the possible mechanism.

Methods: H9C2 cardiomyocytes were treated with ET-1 at concentrations of 10-8, 10-7 and 10-6 mmol/L for 12, 24, 36, and 48 h, respectively. At the same time, oxidative stress injury models were established. After the oxidative stress injury model was established, GW4064 (FXR agonist), siRNA-FXR (the virus interfered with FXR expression) and FXR empty virus were treated for 48 h. CCK-8 method was used to observe the survival rate of cardiomyocytes. Biochemical kit method was used to detect Creatine Kinase (CK) contents, CAT, and mitochondrial activity. Western blot was used to detect the protein expression of SOD1, AMPK and p-AMPK. And real-time PCR was used to detect GPX1 mRNA, GPX3 mRNA, Sirt1 mRNA, PGC-1α mRNA expression levels.

Results: At the concentrations of 10-8, 10-7 and 10-6 mmol/L, ET-1 could induce the decrease of mitochondrial complex I and III activity and increase of CK content in H9C2 cardiomyocytes. Moreover, with the increase of ET-1 concentration and the extension of culture time, the oxidative stress damage of cardiomyocytes became more serious. After ET-1 intervention, the expressions of p-AMPK protein, Sirt1 mRNA and PGC-1α mRNA were decreased. The 2 μmol/L GW4064 could effectively improve the oxidative stress induced by ET-1, and compared with the ET-1 group, the survival rate of H9C2 cardiomyocytes increased obviously. In addition, the CK content was decreased. On the contrary, the mitochondrial complex I and III, and CAT activity increased significantly, and the expressions of SOD1 and p-AMPK protein, Sirt1 mRNA and PGC-1α mRNA increased obviously. However, siRNA-FXR can partially block the improvement effect of FXR agonist on cardiomyocytes injury.

Conclusions: Activation of FXR receptor may reduce the damage of ET-1 on H9C2 cardiomyocytes by activating AMPK signaling pathway.

Background: To explore the efficacy and safety of interferon-α-2b and interleukin-2 combined with chemotherapy in treating patients with metastatic melanoma.

Methods: The patients with metastatic melanoma in control group (N.=52) were treated with conventional DDAVC chemotherapy regimen, while those in combination group (N.=52) received biotherapy with interferon-α-2b and interleukin-2 in addition to the chemotherapy in control group. At the end of the treatments, the serum immune function indicators, short-term efficacy and incidence of adverse reactions were compared between the two groups of patients, and patient's survival was followed up and recorded.

Results: At 1 week after treatment, it was found that the overall response rate in combination group was substantially higher than that in control group (P=0.027). Besides, according to the serologic test results at 1 week after the chemotherapy, T lymphocyte subset activity was enhanced in patients in combination group compared with that before chemotherapy, with no statistically significant difference (P>0.05), but it was notably weakened in control group in comparison with that before chemotherapy (P<0.05). Finally, it was discovered through the log-rank test that the overall survival (OS) rate in combination group was remarkably superior to that in control group (P=0.029), but there was no statistically significant difference in the progression-free survival (PFS) rate between the two groups (P=0.076).

Conclusions: Compared with chemotherapy alone, interferon-α-2b and interleukin-2 combined with chemotherapy can raise the clinical short-term efficacy and long-term OS rate in the patients with metastatic melanoma and alleviate their toxic side reactions, with higher safety.