The angiogenesis-modulating effects of coumarin-derivatives.

Coumarin is a natural compound that is rich in plants. Coumarin and its derivates were reported to have many biological activities, such as anti-bacterial, anti-tumor, and anti-coagulation. In this study, we examined the angiogenic modulating activities of six previously synthesized coumarin derivatives (Compound #1-#6) in zebrafish embryos and further confirmed them in a chick model. According to the survival rate in a zebrafish model, Compound #1 (100 %), #2 (82.5-100 %), and #4 (100 %) showed much less toxicity than Compound #3 (19.2-100 %), #5 (0-100 %), and #6 (0-100 %). Using a green blood vessel fluorescent transgenic fish Tg(fli1:egfp) to record the angiogenesis-modulating effects of Compound #1, #2, and #4, we found that Compound #2 had the highest effects in interfering intersegmental vessel growth, subintestinal vein growth, and caudal vein plexus remodeling. Chick chorioallantoic membrane (CAM) assay also showed that Compound #2 exposure led to a reduction of blood vessel growth. Real-time PCR experiments revealed that Compound #2 significantly changed the expression of vascular growth-related genes flt1, cdh5, and nrp1a in zebrafish. Based on our data from zebrafish and chick models, a new coumarin-derivative (Compound #2) possesses anti-angiogenic activity with low toxicity, but further investigation in mammal models is asked to confirm our findings.

The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival.

BACKGROUND: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p<0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-ß1 levels (p = 0.02), and a trend toward a decrease in IL-1ß levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Arsenic speciation in rice and risk assessment of inorganic arsenic in Taiwan population.

This study assessed the total arsenic content and arsenic speciation in rice to determine the health risks associated with rice consumption in various age-gender subgroups in Taiwan. The average total arsenic levels in white rice and brown rice were 116.6 ± 39.2 and 215.5 ± 63.5 ng/g weight (n = 51 and 13), respectively. The cumulative cancer risk among males was 10.4/100,000. The highest fraction of inorganic/total arsenic content in white rice ranged from 76.9 to 88.2 % and from 81.0 to 96.5 % in brown rice. The current study found different arsenic speciation of rice in southern Taiwan, where the famous blackfoot disease has been reported compared with arsenic speciation from other Taiwan areas. Therefore, rice and other grains should be further monitored in southern Taiwan to evaluate whether arsenic contamination is well controlled in this area.