[Study on tanshinones regulating root-associated microbiomes of Salvia miltiorrhiza].

The plant root-associated microbiomes include root microbiome and rhizosphere microbiome, which are closely related to plant life activities. Nearly 30% of photosynthesis products of plants are used to synthesize root compounds, there is evidence that root compounds regulate and significantly affect the root microbiome Tanshinones are the main hydrophobic components in Salvia miltiorrhiza. In order to study whether these compounds can regulate the root-associated microbiomes of S. miltiorrhiza, our study first identified a white root S. miltiorrhiza(BG) which contains little tanshinones. Retain of the fifth intron of tanshinones synthesis key enzyme gene SmCPS1 leading to the early termination of the SmCPS1 gene, and a stable white root phenotype. Further, wild type(WT) and BG were planted in greenhouse with nutrient soil(Pindstrup, Denmark) and Shandong soil(collected from the S. miltiorrhiza base in Weifang, Shandong), then high-throughput sequencing was used to analyze the root-associated microbiomes. The results showed that the tanshinones significantly affected the root-associated microbiomes of S. miltiorrhiza, and the impact on root microbiomes was more significant. There are significant differences between WT and BG root microbiomes in species richness, dominant strains and co-occurrence network. Tanshinones have a certain repelling effect on Bacilli which belongs to Gram-positive, while specifically attract some Gram-negative bacteria such as Betaproteobacteria and some specific genus of Alphaproteobacteria. This study determined the important role of tanshinones in regulating the structure of root-associated microbiomes from multiple angles, and shed a light for further improving the quality and yield of S. miltiorrhiza through microenvironment regulation.

A meta-analysis comparing the efficacy of entecavir and tenofovir for the treatment of chronic hepatitis B infection.

The efficacy of entecavir and tenofovir in patients with chronic hepatitis B virus (HBV) is inconsistent. To address this issue, we conducted a meta-analysis based on a current review of the literature addressing the efficacy and safety of entecavir and tenofovir. Electronic databases were searched through June 2014 for relevant clinical trials. We included 2 randomized controlled trials, 2 prospective cohort studies, and 7 case-control studies that included 1,656 patients. In the entecavir group, 842 of 992 were nucleos(t)ide-naïve chronic HBV patients, and in the tenofovir group 481 of 664 were nucleos(t)ide-naïve. The virological response to tenofovir was superior to entecavir (RR: 0.82; 95%CI: 0.72-0.93), especially in nucleos(t)ide-naïve chronic HBV patients at 48 weeks (RR: 0.78; 95%CI: 0.65-0.92). Additionally, there was no difference between entecavir and tenofovir for virological response at 24 weeks (RR: 0.87, 95%CI: 0.71-1.05). The alanine aminotransferase normalization rate, serological response, and adverse event rate were also not significantly different between entecavir and tenofovir at 24 or 48 weeks after treatment. These results suggest that tenofovir is a better choice to treat chronic HBV patients than entecavir as it is better able to suppress HBV viral load and has a similar safety profile.

[Molluscicidal effect comparison between TDS and MNSC in field].

OBJECTIVE: To compare the molluscicidal effects between "Luo-wei" (TDS), a plant molluscicide in 4 percent, and metaldehyde and niclosamide (MNSC) in the field. METHODS: A natural ecological environment with Oncomelania hupensis was selected as the test area, the test concentrations of TDS and MNSC were 2.5 g/m3 and 2 ml/m3 respectively by the immersion method; the test doses of TDS and MNSC were 3 g/m2 and 2 ml/m2 respectively by the spray method; the doses of WPN in a control group were 2 g/m3 and 2 g/m2 respectively by the two methods above-mentioned. The molluscicidal effects between TDS and MNSC were compared by using the synchronous design method and parallel comparative method. RESULTS: In the TDS group, the death rate of snails was 90.70% by immersion for 24 hours, reached to 81.40% after spraying for 7 days, and there were no significant differences among the observation time points in molluscicidal effects (P > 0.05). One day after the spraying, the death rate of snails was less in the TDS group compared with that in the MSCN group (P < 0.01), but the death rates of snails were similar in both groups 3 days after the spraying (P > 0.05). In the MSCN group, the death rate of snails was 99.17% by immersion for 24 hours, reached to 66.07% by spraying for 1 day. In the WPS group, the death rate of snails was 97.15% by immersion for 24 hours, reached to 71.43% after spraying for 1 day, and there were no significant differences (both P > 0.05). CONCLUSION: TDS has a good molluscicidal activity and stable efficacy, and the molluscicidal effect of TDS is similar to that of MSCN in the filed, but the molluscicidal sensitivity of TDS is lower than that of MSCN.

Effect of CYP3A5*3 polymorphism on pharmacokinetic drug interaction between tacrolimus and amlodipine.

The objective of this study was to evaluate the effect of the CYP3A5*3 allele on the pharmacokinetics of tacrolimus and amlodipine, and drug-drug interactions between them in healthy subjects. Pharmacokinetic drug interactions between tacrolimus and amlodipine were evaluated in a randomized, 3-period, 6-sequence crossover study in healthy Chinese volunteers according to CYP3A5 genotype. A single-dose and multiple-dose study were designed. A 96-h pharmacokinetic study followed either tacrolimus or amlodipine dose, and the washout periods between the study phases were 14 days. In the single-dose study, apparent oral clearance (CL/F) of tacrolimus (5 mg) in CYP3A5 expressers was 3.8-fold (p = 0.008) higher than that in CYP3A5 non-expressers. Amlodipine decreased mean tacrolimus CL/F in CYP3A5 expressers by 2.2-fold (p = 0.005), while it had no effect on that in CYP3A5 non-expressers. The CL/F of amlodipine in CYP3A5 non-expressers was 2.0-fold (p = 0.001) higher than that in CYP3A5 expressers. Tacrolimus increased mean amlodipine CL/F in CYP3A5 expressers by 1.4-fold (p = 0.016) while it had no effect on that in CYP3A5 non-expressers. Tacrolimus slightly reduced the AUC0-∞ of amlodipine in both CYP3A5 expressers and non-expressers. Dose adjustment of tacrolimus should be considered according to CYP3A5*3 genetic polymorphism when tacrolimus is coadministered with amlodipine.

[Effect of notoginseng radix on expression quantity of TGF-beta1/ Smads and CTGF mRNA in rats with alcoholic liver disease].

OBJECTIVE: To evaluate the effect of Notoginseng Radix on hepatic expression of transforming growth factor beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in rats with alcoholic liver disease (ALD), in order to discuss its protective effect on alcoholic cirrhosis. METHOD: Fifty SD male rats were divided into the normal control group, the model group, the high-dose and low-dose Notoginseng Radix groups (3.0, 12.0 g x kg(-1)) and the magnesium isoglycyrrhizinate group (24 mg x kg(-1)), with 10 rats in each group. Apart from the control group, other groups were administered with ethanol-cornoil-pyrazole for 14 weeks to establish the alcoholic liver disease model. During the establishment of the model, the high-dose and low-dose Notoginseng Radix groups were administered with 12 g x kg(-1) x d(-1) Notoginseng Radix for 14 weeks, once everyday. Efforts were made to detect liver function, pathology with Masson staining, and the expressions of TGF-beta1, Smad3, Smad7 and CTGF mRNA. RESULT: Compared with the rats in model group, rats in Notoginseng Radix groups showed significant reduction in liver ALT, AST, collagen fiber deposition, and TGF-beta1, Smad3 and CTGF mRNA expressions in liver tissues, with the increase in the expression quantity of Smad7 mRNA. There were differences between the Notoginseng Radix groups. No significant difference was observed between the high-dose Notoginseng Radix group and the magnesium isoglycyrrhizinate group. CONCLUSION: Notoginseng Radix can affect TGF-beta1/Smads signaling pathway and reduce the expression of CTGF.

A highly sensitive fluorescent probe for HClO and its application in live cell imaging.

A new rhodamine-based probe 1 was designed and synthesized as a new fluorescent molecular probe for HClO in PBS buffer at physiological condition. The free probe 1 almost nonfluorescence, however, a drastic enhancement of fluorescence intensity was observed in the presence of HClO. The new probe 1 exhibits good sensitivity and selectivity for HClO over other reactive oxygen and/or nitrogen species in PBS buffer, and the probe was successfully applied to image endogeneous HClO in the living cells.

NF-kappaB p65 modulates the telomerase reverse transcriptase in the HepG2 hepatoma cell line.

Nuclear factor-kappa B (NF-kappaB) regulates the expression of various genes, several genes involved in inflammation and tumorigenesis, including those of the liver. A role for NF-kappaB has been implicated in the pathogenesis of hepatocellular carcinoma. This transcription factor can regulate hTERT gene transcription. Expression of hTERT was found to be at high levels in hepatocellular carcinoma. However, positive effects of NF-kappaB on hTERT protein synthesis in HepG(2) cells are unknown. In this study, we show that LPS (specific binding to TLR4 to activate NF-kappaB) was positive for NF-kappaB p65 mRNA expression and activation, and also up-regulated hTERT mRNA and protein expressions at 36h in a dose-dependent manner. In contrast, MG-132 (blocking the activity of 26S proteasome and thereby preventing nuclear translocation of NF-kappaB) significantly inhibited activation of NF-kappaB and mRNA expression. And also reduced the expression of hTERT at both mRNA and protein levels at 36h in a dose-dependent manner. Furthermore, dexamethasone inhibited LPS-induced activation of NF-kappaB and expression of the hTERT in HepG(2) cells. These findings suggest that NF-kappaB may modulate hTERT mRNA level, importantly, in protein level in HepG(2) cells and dexamethasone inhibits LPS-induced hTERT via blocking NF-kappaB.

Simultaneous analysis of amoxicillin and sulbactam in human plasma by HPLC-DAD for assessment of bioequivalence.

A simple and accurate high-performance liquid chromatography with diode array detection-based (HPLC-DAD) method has been developed and validated for simultaneous determination of amoxicillin and sulbactam in human plasma. Sample preparation was involved in protein precipitation with acetonitrile followed by one-step extraction procedure. Chromatographic separation was achieved on a C18 column with an isocratic mobile phase consisting of water (containing 30 mM potassium dihydrogen phosphate, pH 2.8) and acetonitrile. The detection wavelengths of a diode array detector were set at 210 nm for amoxicillin and sulbactam, and 263 nm for the internal standard (cefadroxil). The method was validated for linearity, accuracy, precision, and stability. The calibration curve was linear from 0.163 to 14.7 µg/mL with correlation coefficient squared of 0.9991 for amoxicillin and 0.250-15.0 µg/mL with correlation coefficient squared of 0.9988 for sulbactam using 500 µL plasma samples. The lower limit of quantification was 0.163 and 0.250 µg/mL for amoxicillin and sulbactam, respectively. The imprecisions of intra- and inter-day validations for amoxicillin and sulbactam were <11% and their accuracies (%) were within the range of 95.4-105.7%. Mean recoveries were 75.9, 72.8, and 70.0% for amoxicillin, sulbactam, and cefadroxil, respectively. The established method was successfully applied to a bioequivalence study of two combination formulations of amoxicillin and sulbactam pivoxil in healthy male volunteers.