Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms.

BACKGROUND AND PURPOSE: Recent studies have shown that resveratrol increased endothelial progenitor cells (EPCs) numbers and functional activity. However, the mechanisms remain to be determined. Previous studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involves activation of telomerase. Therefore, we investigated whether resveratrol inhibits the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. EXPERIMENTAL APPROACH: After prolonged in vitro cultivation, EPCs were incubated with or without resveratrol. The senescence of EPCs were determined by acidic beta-galactosidase staining. The bromo-deoxyuridine incorporation assay or a modified Boyden chamber assay were employed to assess proliferative or migratory capacity, respectively. To further examine the underlying mechanisms of these effects, we measured telomerase activity and the phosphorylation of Akt by western blotting. KEY RESULTS: Resveratrol dose dependently prevented the onset of EPCs senescence and increased the proliferation and migration of EPCs. The effect of resveratrol on senescence could not be abolished by eNOS inhibitor or by an oestrogenic receptor antagonist. Resveratrol significantly increased telomerase activity and Akt phosphorylation. Pre-treatment with the PI3K inhibitor, LY294002, significantly attenuated resveratrol-induced telomerase activity. CONCLUSIONS AND IMPLICATIONS: Resveratrol delayed the onset of EPC senescence and this effect was accompanied by activation of telomerase through the PI3K-Akt signalling pathway. The inhibition of EPCs senescence by resveratrol might protect EPCs against dysfunction induced by pathological factors in vivo and improve EPC functional activities in a way that may be important for cell therapy.

Influences of RFA combined with TACE on the HIF-1α and EGR level of patients with primary hepatic carcinoma.

OBJECTIVE: To discuss the influences of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization on the expression level of immunity and hypoxia-inducible factor (HIF-1a) and early growth response protein2 (EGR2) of patients with hepatocarcinoma. PATIENTS AND METHODS: Patients with primary hepatic carcinoma treated in our hospital from 2011 to 2014 were divided into research group (RFA+TACE) and control group (TACE) according to different therapy methods, with 72 patients in each group. Then, the immunity functions were detected before treatment and 3 months after treatment, the expression level of HIF-1a, EGR-2, the alpha fetal protein (AFP), the therapeutic effect, and incidence of adverse reaction in near and specific future were compared between two groups. RESULTS: After treatment, the ratio of CD3+ and CD4+T cells, specific vale of CD4/CD8, and NK cell population in research group were more than those in control group, while the ratio of CD8+T cells was less than that in control group with statistical significance. Meanwhile, the expression levels of HIF-1a (F between-group*time point = 5.353, p = 0.043), EGR-2 (F between-group*time point = 4.385, p = 0.044), and AFP (F between-group*time point = 4.205, p = 0.045) had difference with statistical significance. Moreover, the recent therapy response rate in research group was 76.4%, which was higher than that in control group (50.0%), with significant difference (χ2 = 10.784, p = 0.029), while the difference of long-term therapeutic effect between two groups has statistical significance (χ2 = 7.439, p = 0.005). CONCLUSIONS: The treatment of primary hepatic carcinoma by TACE combined with RAF therapeutic schedule was helpful in improving organic immunity, decreasing tumor angiogenesis and reducing tumor cell proliferation speed to improve the short- and long-term therapeutic effects.

Salvianolic acid A inhibits platelet activation and arterial thrombosis via inhibition of phosphoinositide 3-kinase.

BACKGROUND AND OBJECTIVE: Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia miltiorrhiza Bunge, a herb that is widely used for atherothrombotic disease treatment in Asian medicine. As platelets play pivotal roles in atherothrombogenesis, we studied the effect of SAA on platelet activation and its underlying mechanisms. METHODS AND RESULTS: SAA dose-dependently inhibited platelet aggregation induced by ADP, thrombin, collagen and U46619. It reduced ADP-enhanced platelet P-selectin expression and fibrinogen binding, which consequently hampered ADP-induced platelet-leukocyte aggregation. SAA also inhibited platelet spreading on fibrinogen, a process mediated by outside-in signaling. Under an arterial shear rate of 1000 s(-1), SAA decreased platelet adhesion on collagen surfaces by approximately 40%. Western blot analysis showed that SAA, like the phosphoinositide 3-kinase (PI3K) inhibitors LY294002 and TGX-221, potently inhibited PI3K, as shown by reduced Akt phosphorylation. The in vitro findings were further evaluated in the mouse model of arterial thrombosis, in which SAA prolonged the mesenteric arterial occlusion time in wild-type mice (35 + or - 2 min without SAA and 56 + or - 4 min with SAA; P < 0.01). Interestingly, SAA could even counteract the shortened arterial occlusion time in Ldlr(tm1Her) mutant mice (21 + or - 2 min without SAA and 45 + or - 4 min with SAA; P < 0.01). CONCLUSIONS: SAA inhibits platelet activation via the inhibition of PI3K, and attenuates arterial thrombus formation in vivo. Our data suggest that SAA may be developed as a novel therapeutic agent for the prevention of thrombotic disorders.

Acute adrenal insufficiency in association with pancreatic carcinoma.

Addison's disease secondary to metastatic cancer to the adrenal gland is underdiagnosed. Prompt diagnosis and treatment is essential and could enhance the quality of life. Cases of adrenal insufficiency produced by metastatic carcinoma are unusual, despite the frequency of carcinomatous metastases to the adrenal glands. The clinical features of adrenal insufficiency are relatively nonspecific and can be easily overlooked in a patient with a malignant neoplasm. We report herein the case of a middle-aged man who presented with adrenal insufficiency in association with pancreatic carcinoma. To our knowledge, this is the first reported case of adrenal insufficiency occurring with adenocarcinoma of the pancreas.

Structures of two new diterpenoid dimers from bulbs of Fritillaria ebeiensis.

Two new ent-kauranoid diterpenoid dimers, fritillebin C (1) and fritillebin D (2), were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu and G.Q. Ji. Their structures were determined to be ent-16beta-hydroxy-kauran-17-yl ent-16beta3-kauran-17-oate (1); ent-16alpha-hydroxy-kauran-17-yl ent-16beta-kauran-17-oate (2) by means of spectral analysis and chemical evidence.