Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality?

BACKGROUND: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. MATERIAL AND METHODS: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses. RESULTS: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta2 caused by the intervention were considered small to medium. CONCLUSION: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. © 2017 BioFactors, 44(2):137-147, 2018.

Evaluation of the antiangiogenic, anti-inflammatory, and antinociceptive activities of morin.

Morin displayed significant inhibition of chick chorioallantoic membrane (CAM) angiogenesis and was able to increase the endostatin level in human umbilical vein endothelial cells (HUVECs). Morin was shown to contain an in vivo anti-inflammatory activity using a carrageenan-induced air pouch model in mice. Antinociceptive activity of morin was also assessed using an acetic acid-induced writhing test in mice. Collectively, morin possesses antiangiogenic, in vivo anti-inflammatory, and antinociceptive activities.

A phase I pharmacokinetic and pharmacodynamic study of CKD-732, an antiangiogenic agent, in patients with refractory solid cancer.

We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m(2) given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m(2). The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m(2) according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m(2) and a BAD of 5 mg/m(2).

[Effects of Erbie San on Walker-256 liver cancer and adjustment to unbalance of VEGF/endostatin in rats].

OBJECTIVE: To investigate the anticancer effects of Erbie San on the rats bearing Walker-256 liver cancer and the potential mechanism of its angiogenesis effects. METHOD: Wistar rats bearing Walker-256 liver cancer were used in this study. The experimental groups were treated with Erbie San 1.25, 2.5, 5 g x kg(-1) x d(-1), and 5-Fluorouracil injection 75 mg x kg(-1), respectively. The tumor's weight, the expression of VEGF, Endostatin and the ratio of VEGF/endostatin in serum of each groups were observed. RESULT: Compared to the model group, Erbie San 2.5, 5 g x kg(-1) x d (-1) and 5-Fluorouracil injection groups can reduce the tumor's weight significantly (P<0.05 or P<0.01). The expression of VEGF was reduced, while endostatin was increased, and the ratio of VEGF/endostatin was reduced (P<0.05 or P<0.01). CONCLUSION: Erbie San can effectively inhibit the growth of Walker-256 liver cancer of rats and can inhibit the expression of VEGF but increase the expression of endostatin, which suggest that Erbie San has the inhibition of angiogenesis which is responsible for its anticancer effects.

[Pathological basis of qi-deficiency and blood stasis syndrome in patients with non-small cell lung cancer viewing from tumor metastasis related factors].

OBJECTIVE: To observe the expressions of tumor metastasis related factors (TMRF) in peripheral blood of patients with non-small cell lung cancer (NSCLC) for exploring the molecular mechanism for genesis of qi-deficiency and blood stasis (QDBS) syndrome in patients. METHODS: Eighty selected NSCLC patients of stage II B/III were differentiated into the QDBS group and the non-QDBS group according to the Chinese medicine syndrome differentiation criteria, 40 in each group. The serum levels of vascular endothelial growth factor (VEGF), endostatin (ES) and soluble intercellular adhesive molecule-1 (slCAM-1) in patients were detected by ELISA, and the expression of adhesive molecule CD44 in peripheral blood was determined using flow cytometry. RESULTS: Serum levels of VEGF (1002.78 +/- 312.08 ng/L), ES (120.88 +/- 20.00 microg/L), slCAM-1 (531.78 +/- 213.37 microg/L) and CD44 (136.65 +/- 29.60) were significantly higher in patients of QDBS group than in patients of non-QDBS group (653.18 +/- 318.99 ng/L, 98.29 +/- 23.92 microg/L, 409.36 +/- 167.65 microg/L and 98.46 +/- 20.64, respectively, P<0.01). CONCLUSION: Objective inner links are found between the QDBS syndrome and TMRF in NSCLC patients; serum levels of VEGF, ES, slCAM-1 and CD44 can be served as the microcosmic basis for QDBS syndrome differentiation.

Myristica malabarica heals stomach ulceration by increasing prostaglandin synthesis and angiogenesis.

Earlier we had shown that on the 3 (rd) day of its administration to mice, indomethacin (18 mg kg (-1), P. O.) produced maximum stomach ulceration with a damage score of 3.46, which was reduced by a 3-day treatment with the methanol extract of Myristica malabarica (40 mg kg (-1), P. O.) and omeprazole (3 mg kg (-1), P. O.) to 0.95 and 0.82, respectively. Presently, we investigated the possible role of the test samples in modulating PG synthesis and angiogenesis for their healing action. The ulceration was found to be associated with suppression of PGE (2), VEGF and vWF VIII, and an increase in EGF and endostatin levels. Treatment with the plant extract reversed all these parameters accounting for its healing activity. However, despite providing similar healing, omeprazole did not alter these parameters.