ABSTRACT
AIMS: The antihypertensive mechanism (s) of the epigallocatechin-3-gallate (EGCG), a major effective component in green tea, might associate with microRNAs (miRNAs). Here, we aimed to investigate which microRNA in aorta of spontaneously hypertensive rats (SHRs) were modulated by administration of EGCG and its mechanism. MAIN METHODS: The pharmacokinetic behaviors of EGCG and epigallocatechin (EGC) in Sprague-Dawley rats were analyzed by HPLC and DRUG AND STATISTICS software. Blood pressure of SHRs was monitored by the tail-cuff method, the miRNomes of aorta from SHRs was analyzed with deep sequencing, and expression of hypertension-associated miRNAs with significant change and their host genes and target genes were validated by real-time PCR and Western blot. KEY FINDINGS: The plasma deposition of EGCG and EGC best fitted a mono-compartmental model with maximum plasma concentration post-dose (Cmax, 6.65 vs 4.45⯵g/ml) and the corresponding time (Tmax, 15 vs 10â¯min). Systolic blood pressure (SBP) of SHRs decreased to the lowest point by 34.04â¯mmHg and recovered by 23.39â¯mmHg after 15 and 30â¯min of administration at dose of 300â¯mg/kg BW EGCG, respectively, and it decreased again at 60â¯min and recovered at time 2â¯h. Total 35 upregulated and 18 downregulated miRNAs were identified compared to the control group (pâ¯<â¯.01) after EGCG administration. Expression of hypertension-associated miRNA-126a-3p and miRNA-150-5p were further validated. In turn, their host gene and target genes were up-regulated and down-regulated, respectively. SIGNIFICANCE: Our results indicated that miRNA-150-5p might be involved in the antihypertensive effect of EGCG through SP1/AT1R pathway.
Subject(s)
Antihypertensive Agents/pharmacology , Aorta/metabolism , Catechin/analogs & derivatives , Gene Expression Regulation/drug effects , Hypertension/genetics , MicroRNAs/genetics , Tea/chemistry , Animals , Aorta/drug effects , Biomarkers/metabolism , Blood Pressure/drug effects , Catechin/pharmacology , Gene Expression Profiling , Hypertension/drug therapy , Hypertension/pathology , Male , Rats , Rats, Inbred SHR , Rats, Sprague-DawleyABSTRACT
Objective To predict the trend of hepatocellular carcinoma (HCC) mortality and investigate the features of its mortality including age, period, and birth cohort in males living in Haimen city of Jiangsu province, China. Methods Grey model (GM) was modeled using standardized mortality rate (SMR) of HCC from 1993 to 2006, and was applied to predicting SMR until 2012. Based on the mortality density (MD) for a four-year period, the goodness-of-fit of models and comparisons between models were evaluated so as to obtain the best one among these models including the effects of intercept, age-period-cohort (APC) , age-period (AP), age-cohort (AC),period-cohort(PC), and APC. Both APC full model and the best model were used to estimate effects of age, period, and cohort on HCC mortality. In addition, MD from 2005 to 2012 was predicted by the best model. Results Predictions based on GM (1,1 )showed that SMR was 48.578 per 100 000 population (relative error=-1.267% ) in 2007 year, which declined between 2008 and 2012. The lowest value was 45.578 per 100 000 people (in the 2012 year). The results of fitted models and comparisons between models showed that AP model was the best one (△G2=9.065,AIC=202.544). The curvatures of the effects of the three factors from APC model suggested that significances existed in changes of curvatures of 36.5-40.5 years old- (-0.368) and 64.5-68.5 years old-(-0.489) as well as in the change of 1956-1959 birth cohort (C21949.5. 1967.5=-0.492). The estimation of relative risks for AP model showed that the age effects were upward to 64.5-68.5 years old-, then downward; and that the period effects were found to be declined between 1993 and 2004. Predictions based on AP model suggested the decrease of HCC mortality. Conclusion The slightly decreasing trend of HCC mortality for males might be explained by age, period and a minor birth cohort effects in Haimen of China.
ABSTRACT
OBJECTIVE: To investigate the effects of processing Phellodendron anurene with salt on anti-gout. METHOD: The mouse serum uric acid level and liver xanthine oxidase activity were used to evaluate anti-gout effects of raw and processing P. amurense with salt. RESULT: Both raw and processing P. amurense with salt reduced serum uric acid levels in the in hyperuricemic mice, and inhibited activities of liver xanthine oxidase at the low and high doses respectively, thus exhibiting anti-gout effects. Moreover, they showed the tendency to decrease the uric acid levels in the normal animal only at the high dose. The latter was a little weaker than the former. CONCLUSION: Processing with salt might not significantly change anti-gout effect of P. amurense.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Gout Suppressants/pharmacology , Hyperuricemia , Phellodendron/chemistry , Xanthine Oxidase/metabolism , Animals , Drugs, Chinese Herbal/isolation & purification , Hot Temperature , Hyperuricemia/blood , Hyperuricemia/enzymology , Liver/enzymology , Male , Mice , Plants, Medicinal/chemistry , Random Allocation , Sodium Chloride , Technology, Pharmaceutical/methods , Uric Acid/bloodABSTRACT
<p><b>OBJECTIVE</b>To explore the association of hepatocellular carcinoma (HCC) with environmental factors through analyzing birth order data from pedigree sibships.</p><p><b>METHODS</b>A birth order study was conducted based on the methods of Greenwood and Haldane for 100 probands and 22 affected siblings from 100 pedigrees in a cohort which was followed up for 8 years in Haimen, Jiangsu, China.</p><p><b>RESULTS</b>The findings from the Greenwood method suggested that there was a tendency for cases of HCC to concentrate at lower birth orders of 1 to 3. With the effects of hepatitis B virus on the birth orders being controlled, the same tendency was also observed. The results from Haldane method showed that difference between actual value and expected value of 6A was more than the double standard deviation. Sigma 6A(actual value) = 1,806, Sigma 6A(expected value) = 1,988, the absolute value of (Sigma 6A(actual value) - Sigma 6A(expected value))/the square root of Sigma V6A = 2.1657 (0.02 < P < 0.05). The actual value of 6A was lower than the expected value of 6A suggesting that individuals at lower birth orders were at a higher risk of suffering from HCC. In addition, through data from ecologic research, there was a decreasing tendency of mortality of HCC within 10 years after the prevalence of tap water in Haimen city. The correlation coefficient by Spearman test was -0.818 (P < 0.01). The contribution of the quality of drinking water in the locality to the onset of HCC was found among people born in earlier period.</p><p><b>CONCLUSIONS</b>There was a tendency that the onset of HCC cases concentrating was at lower birth orders in this research, which was inconsistent with several reports of foreign authors' which showed a reverse tendency. According to the ecological results, it was suggested that long-term drinking of ditch-water was responsible for the tendency of cases of HCC concentrating at lower birth orders. There were also certain effects of environmental factors exerted on the onset of HCC being discovered.</p>