'GLL-1'为'禾荔'中选育出的一个优质晚熟芽变新种质.为探讨'GLL-1'果实成熟期延迟的遗传基础,该研究以'禾荔'和'GLL-1'为实验材料,克隆花色素苷合成途径结构基因LcUFGT,并对其进行生物信息学预测及分析,同时通过qRT-PCR对LcUFGT基因在果实发育不同阶段的表达进行研究,分析LcUFGT的表达对突变体果实发育速度的影响.结果表明:(1)LcUFGT基因ORF长1359 bp,编码453个氨基酸,推测蛋白质分子量约为50.16 kD.(2)序列比对发现所编码蛋白与'禾荔'等荔枝品种高度保守,在蛋白的C端具有PSPG盒.(3)在果实发育成熟进程中,'禾荔'和'GLL-1'果皮逐渐退绿转红,两者LcUFGT基因的表达量都呈先上升后下降的表达趋势,然而,'禾荔'LcUFGT基因的表达量在花后56 d显著增加,突变体'GLL-1'LcUFGT基因的表达量在花后67 d显著增加,LcUFGT基因在突变体'GLL-1'中显著上升表达的时间比'禾荔'延迟,且与果实发育延迟基本一致.以上结果表明,LcUFGT基因在荔枝果皮着色过程中发挥重要作用,是果实着色的关键基因之一,突变体'GLL-1'中的延迟表达是引起突变体晚熟的原因之一.
Rhein, a major bioactive compound of many medicinal herbs and the prodrug of diacerein, is often used with low dose of methotrexate as drug combination to treat rheumatoid arthritis. In this study, potential drug-drug interaction between methotrexate and rhein was investigated based on organic anion transporters (OAT). Our study demonstrated that rhein acyl glucuronide (RAG), the major metabolite of rhein in the human blood circulation, significantly inhibited the uptake of p-aminohippurate in hOAT1 transfected cells with IC50 value of 691 nM and estrone sulfate uptake in hOAT3 transfected cells with IC50 value of 78.5 nM. As the substrate of both hOAT1 and hOAT3, the methotrexate transport was significantly inhibited by RAG in hOAT1 transfected cells at 50 μM and hOAT3 transfected cells at 1 μM by 69% and 87%, respectively. Further in vivo study showed that after co-administrated with RAG in rats the AUC0-24 values of methotrexate increased from 3109 to 5370 ng/mL*hr and the t1/2 was prolonged by 40.5% (from 7.4 to 10.4 h), demonstrating the inhibitory effect of RAG on methotrexate excretion. In conclusion, rhein acyl glucuronide could significantly decrease the transport of methotrexate by both hOAT1 and hOAT3. The combination use of rhein, diacerein or other rhein-containing herbs with methotrexate may cause obvious drug-drug interaction and require close monitoring for potential drug interaction in clinical practice.
BACKGROUND:The prognosis and management of hepatic fibrosis are closely related to the stage of the disease. The limitations of liver biopsy, which is the gold standard for treatment, include its invasiveness and sampling error. Ultrasound elasticity might be the most promising imaging technology for the noninvasive and accurate assessment of hepatic fibrosis. Real-time tissue elastography (RTE) measures the relative stiffness of the tissue in the region of interest caused by the heartbeat. Many studies have verified that RTE is useful for the diagnosis of hepatic fibrosis in patients with chronic hepatitis C (CHC).PURPOSE:To determine the formula of the liver fibrosis index for chronic hepatitis B (BLFI) and to validate the diagnostic accuracy of the BLFI for hepatic fibrosis compared with the liver fibrosis index (LFI).MATERIALS AND METHODS:RTE was performed in 747 prospectively enrolled patients with chronic hepatitis B (CHB) or cirrhosis from 8 centers in China; 375 patients were analyzed as the training set, and 372 patients were evaluated as the validation set. The fibrosis stage was diagnosed from pathological specimens obtained by ultrasound-guided liver biopsy. Nine image features were measured from strain images, and the new formula for the BLFI was obtained by combining the nine imaging features of the RTE images using multiple regression analysis of the training set. The BLFI and LFI were compared with the pathological fibrosis stage at diagnosis, and the diagnostic performances of the indexes were compared.RESULTS:The Spearman correlation coefficient between the BLFI and hepatic fibrosis stages was significantly positive (r = 0.711, p < 0.001), and significant differences were present between all disease stages. The areas under the receiver-operating characteristic (AUROC) curves of the BLFI and LFI for predicting significant fibrosis (S0-S1 vs. S2-S4) were 0.858 and 0.858, respectively. For cirrhosis (S0-S3 vs. S4), the AUROC curves of the BLFI and LFI were 0.868 and 0.862, respectively.CONCLUSION:The results of this large, multicenter study confirmed that RTE is valuable for the diagnosis of hepatic fibrosis in patients with CHB. However, the diagnostic efficiencies of the new BLFI and the original LFI, which were based on CHC, for the assessment of CHB hepatic fibrosis were similar; thus, the LFI has the potential to be used to directly evaluate the extent of hepatic fibrosis in patients with CHB.