Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including antioxidant, anti-in ammatory, antitumor and chemoprotective effects. However, its clinical applications were initially limited by its poor absorption, rapid metabolism and rapid systemic elimination. To improve the bioavailability of curcumin, new approaches have to be taken. Three curcumin derivatives (mPEG 2k -Gly-Cur, mPEG 2k -Gly-Cur-OA and Cur-OA 2 ) were synthesized in this paper, and their biodistribution was analyzed by HPLC technique. In mice, all compounds were administered i.v. (equal to free curcumin 20 mg/kg), and the results confirmed the rapid clearance of free curcumin in blood and liver, but it was beyond our expectation to observe the remarkable lung tissue accumulation effect of curcumin, with C max = 193.12 μg/g after 30 min of administration, and can still be detected with 8.25 μg/g after 4 h. PEGylation can extend the circulation half-life of curcumin, but the effect was limited attributed to the low molecular weight of PEG. PEG co-modify with Oleic acid can increase liver uptake of curcumin. Oleic acid alone esterified curcumin can significantly increase curcumin level in liver, and can be detected with 15.77 μg/g after 4 h. In conclusion, our finding suggested that free curcumin have the lung accumulation property, which implied lung disease therapeutic effect; and it would also be suitable for curcumin to explore pulmonary delivery system so as to increase its bioavailability. Additionally, Oleic acid esterification method could be another way to enhance curcumin activity in certain specific organs, especially in liver.
To test the possible association between reversion-inducing cysteine-rich protein with Kazal motifs (RECK) genetic variants and susceptibility as well as the chemotherapy response status to in patients with advanced non-small cell lung cancer (NSCLC). We recruited 304 patients who were histologically diagnosed as advanced NSCLC (IIIa, IIIb, and IV stage) in our hospital from September 2003 to January 2008. We also enrolled 409 sex- and age-matched healthy volunteers as controls. RECK Gene Polymorphisms were determined. Only the genotype distributions and allele frequencies of rs10814325 T>C were significantly different between NSCLC and controls (both P < 0.001). By multivariate analyses, markedly higher risk for NSCLC was observed in rs10814325 CC genotype (adjusted OR = 2.302, P = 0.012, with TT as reference) after adjustment with age, sex, smoking status, histology, differentiation, and stage. Haplotypes analyses showed that the A(rs11788747)-G(rs16932912)-C(rs10814325) and A(rs11788747)-A(rs16932912A)-C(rs10814325) were associated with higher risk for NSCLC; however, G(rs11788747)-G(rs16932912)-T(rs10814325) and G(rs11788747)-A(rs16932912)-T(rs10814325) haplotypes showed significantly protective roles in the NSCLC risk. The genotype and the allele frequencies of RECK gene were not significantly different between chemotherapy responder and non-responders. Multivariate logistic regression analysis showed no association between the RECK polymorphism and chemotherapy response status in this study. To the best of our knowledge, this is the first study documenting the etiological role of RECK genetic polymorphisms in NSCLC.
Purpose: To evaluate the effect of epigallocatechin gallate (EGCG) on sepsis-induced liver injury in a rat model of sepsis established by cercal ligation and puncture (CLP
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