Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa)

published_or_final_versio

Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

published_or_final_versio

Discovery of a ROCK inhibitor, FPND, which prevents cerebral hemorrhage through maintaining vascular integrity by interference with VE-cadherin

published_or_final_versio

Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

published_or_final_versio

Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC

Author name used in this publication: Shun Wan Chan2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Study of the fire behaviour of structures strengthened with NSM

In recent years, Near Surface Mounted (NSM) Fiber Reinforced Polymer (FRP) is increasingly used to enhance the flexural strength and shear resistance of deficient reinforced concrete (RC) and prestressed concrete (PC) members. The technique is based on the concept of embedding FRP bars - with circular, square or rectangular cross section - into grooves made in the concrete cover of the elements to be strengthened. The dimensions of the grooves are based on the available concrete cover and the fact that the FRP bars should be completely embedded. Advantages of using NSM FRP compared to externally bonded FRP reinforcement (FRP EBR) are the better bond characteristics, more ductile behaviour, possibility of anchoring the reinforcement into adjacent RC members, limited installation time, better resistance to mechanical damage, fire and accidental impact. The structural behaviour of RC members strengthened with NSM under normal environmental conditions is getting more and more documented satisfactory. However structures and particularly buildings, may also be subjected to fire. FRPs used in structural applications with reinforced concrete are generally not expected to perform well at elevated temperatures. Of the constituent materials, the fibres in FRP materials perform significantly better at elevated temperatures than the polymer binder of these components. When thermoset resins commonly used in structural FRPs, reach or exceed their glass transition temperature (Tg) they experience significant loss in both strength and stiffness, as well as bon properties. Typical Tg values may range between 65 and 150°C, which are low values compared to acting temperatures in fire conditions. For EBR and NSM applications, bond performance is of critical importance for the overall performance of the strengthened members. In the case of NSM the FRP reinforcement is not longer externally bonded, but in slits. This offers extra opportunities for fire protection. Although this advantage has been repeatedly suggested, further experimental evidence is needed to confirm this hypothesis

VEGFR tyrosine kinase inhibitor II (VRI) induced vascular insufficiency in zebrafish as a model for studying vascular toxicity and vascular preservation

In ischemic disorders such as chronic wounds and myocardial ischemia, there is inadequate tissue perfusion due to vascular insufficiency. Besides, it has been observed that prolonged use of anti-angiogenic agents in cancer therapy produces cardiovascular toxicity caused by impaired vessel integrity and regeneration. In the present study, we used VEGFR tyrosine kinase inhibitor II (VRI) to chemically induce vascular insufficiency in zebrafish in vivo and human umbilical vein endothelial cells (HUVEC) in vitro to further study the mechanisms of vascular morphogenesis in these pathological conditions. We also explored the possibility of treating vascular insufficiency by enhancing vascular regeneration and repair with pharmacological intervention. We observed that pretreatment of VRI induced blood vessel loss in developing zebrafish by inhibiting angiogenesis and increasing endothelial cell apoptosis, accompanied by down-regulation of kdr, kdrl and flt-1 genes expression. The VRI-induced blood vessel loss in zebrafish could be restored by post-treatment of calycosin, a cardiovascular protective isoflavone. Similarly, VRI induced cytotoxicity and apoptosis in HUVEC which could be rescued by calycosin post-treatment. Further investigation of the underlying mechanisms showed that the PI3K/AKT/Bad cell survival pathway was a main contributor of the vascular regenerative effect of calycosin. These findings indicated that the cardiovascular toxicity in anti-angiogenic therapy was mainly caused by insufficient endothelial cell survival, suggesting its essential role in vascular integrity, repair and regeneration. In addition, we showed that VRI-induced blood vessel loss in zebrafish represented a simple and effective in vivo model for studying vascular insufficiency and evaluating cancer drug vascular toxicities.Department of Applied Biology and Chemical Technolog

Sailuotong prevents hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>)-induced injury in EA.Hy926 cells

© 2017 by the authors; licensee MDPI, Basel, Switzerland. Sailuotong (SLT) is a standardised three-herb formulation consisting of Panax ginseng, Ginkgo biloba, and Crocus sativus designed for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H2O2)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1-50 µg/mL) significantly suppressed the H2O2-induced cell death and abolished the H2O2-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H2O2 (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1-50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H2O2-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H2O2-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed

Uptake and Protective effects of Ergothioneine in Human Endothelial Cells

Ergothioneine is a thiourea derivative of histidine found in food, especially mushrooms. Experiments in cell-free systems and chemical assays identified this compound as a powerful antioxidant. Experiments were designed to test the ability of endothelial cells to take up ergothioneine and hence benefit from protection against oxidative stress. Reverse-transcription polymerase chain reaction and Western blotting demonstrated transcription and translation of an ergothioneine transporter in human brain microvascular endothelial cells (HBMECs). Uptake of [H-3] ergothioneine occurred by the organic cation transporter novel type-1 (OCTN-1), was sodium-dependent, and was reduced when expression of OCTN-1 was silenced by small interfering RNA (siRNA). The effect of ergothioneine on the production of reactive oxygen species (ROS) in HBMECs was measured using dichlorodihydrofluorescein and lucigenin, and the effect on cell viability was studied using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. ROS production and cell death induced by pyrogallol, xanthine oxidase plus xanthine, and high glucose were suppressed by ergothioneine. The antioxidant and cytoprotective effects of ergothioneine were abolished when OCTN-1 was silenced using siRNA. The expression of NADPH oxidase 1 was decreased, and those of glutathione reductase, catalase, and superoxide dismutase enhanced by the compound. In isolated rat basilar arteries, ergothioneine attenuated the reduction in acetylcholine-induced relaxation caused by pyrogallol, xanthine oxidase plus xanthine, or incubation in high glucose. Chronic treatment with the compound improved the response to acetylcholine in arteries of rats with streptozotocin-induced diabetes. In summary, ergothioneine is taken up by endothelial cells via OCTN-1, where the compound then protects against oxidative stress, curtailing endothelial dysfunction.Department of Applied Biology and Chemical Technolog