OBJECTIVE: To investigate the in-vitro release behavior of venetoclax preparations, the pharmacokinetic processes and the correlations between in-vitro release and in-vivo absorption of venetoclax in Beagle dogs. METHODS: The dissolution curves of venetoclax preparations in different dissolution media were studied. HPLC method was established for the determination of venetoclax in Beagle dogs, and the pharmacokinetics were studied for commercial venetoclax tablets in Beagle dogs under fed and fasted states.The IVIVC study was carried out by linear regression of cumulative in-vitro drug release and in-vivo absorption accumulation percentage data. RESULTS: The in-vitro release behavior among venetoclax formulation in 4 dissolution media were significant difference. The simple, accurate and rapid analysis method for venetoclax blood samples was established. The fed group and the fasted group AUC0→∞ were (32.38±5.87) and (27.70±6.32) mg·h·L-1, the concentration of peak were (4.04±0.78) and (3.72 ±0.69) μg·mL-1, the peak time were (6.01±1.04) and (4.27±0.92) h, respectively, and there was obvious difference (P<0.05) in AUC0→∞ and the peak time between two group. Percentage of in-vivo absorption was in good agreement with in-vitro release in pH 6.8 0.2%SDS media. CONCLUSION: The study shows that food could improve the bioavailability of venetoclax formulation; 0.2%SDS pH 6.8 media (paddle, 75 r·min-1) is the in-vivo release of venetoclax associated with the in-vitro release condition.

Objective: To establish an HPLC fingerprint analysis method of Zhishi Xiebai Guizhi Decoction (ZXGD) and the content determination method of 10 index components of the decoction, and carry out the relevant evaluation and analysis. Methods: HPLC method was used to establish the fingerprint analysis method of ZXGD and then similarity evaluation was carried out. Ten index components of the decoction were determined, the influence of the change of compatibility of medicinal materials on the content of index components was analyzed. Cluster analysis and other chemometrics methods were used to analyze the relevant data and evaluate the impact and value of quality control related indicators of ZXGD. Results: The similarity of 10 batches of samples ranged from 0.376 to 0.990, and that of five batches was more than 0.9, which indicated that the similarity of 10 batches of samples was quite different. In 10 batches of samples, S1, S2, S3, S5, S6, S8 and S10 were in one group, S4 and S9 were in one group, S7 was in one group. In this study, 30 characteristic peaks were calibrated, and principal components 1-6 was the main factor affecting the quality evaluation of medicinal materials. Among the 30 characteristic peaks, peak 21 (neohesperidin), 26, 29 (honokiol), 3, 23, 17, 30 (magnolol), 5, 24 (coumarin), 28, and 7 were the key components. The results showed that except quercetin, the other nine components had good linear relationship, precision, stability and repeatability in the range of mass concentration. Different compatibilities could increase or inhibit the dissolution of related components in medicinal materials. Conclusion: The HPLC method can be used for the simultaneous determination of ten chemical components in ZXGD. The method is efficient, accurate and reproducible, and can be used for the quality control and evaluation of ZXGD.

Microarray technology are being performed more widely than ever before on many areas in lifescience,although the technology is still evolving,the challenge of performing a microarray experiment is no longer in the data generation,but in extracting useful information and utilizing it to get the results with biological meanings.Some methods and tools used for expressional microarray data mining based on previous work were summarized.These methods include gene clustering,GO analysis,regulating pathway analysis,and related algorithm.We hope this can be helpful for those researchers who are implementing expressional microarray for biological analysis.

Objective To evaluate the situation of blood concentration detection in Zunyi city by the way of analyzing the practice of blood concentration detection for the past 4 years .Methods The bood samples of 194 928 persons who were voluntary blood donators since full implementation of centralized blood test from February 2011 to December 2014 were analysed .Results The unqualified rates of the 5 detection indicators from the seven blood center banks were closed to the centre blood station ,which was rang from 3 .15% to 4 .85% ,the total unqualified rate was 3 .72% and no significant difference was found(P> 0 .05) .Since the concentration of blood detection ,blood donators in the 7 blood center blood banks increased year by year .Conclusion Blood concen-tration detection improves the blood test quality in this single region ,and promotes the development of blood donation career .

Traditional Chinese medicine Curcuma Zedoary ( E'Zhu) contains essential oil, curcuminoid and other effective constituents, with such pharmacological actions as anti-platelet aggregation, lowing blood lipid, anti-oxidation and anti-inflammation. In recent years, studies have showed that certain extracts and chemical components of E'Zhu could mitigate myocardial cell mitochondria injury and protect vascular endothelium by enhancing heme oxygenase-1 activity, inhibit nuclear factor NF-kappaB, target genes interleukin-associated kinase-1 (IRAK-1), tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), reduce inflammatory infiltration, and inhibit growth factor-induced smooth muscle cells (SMCs) proliferation and migration by impacting oxidation of cellular phosphatases. Due to its different functions in vascular endothelial cells and smooth muscle cells, E'Zhu has been applied in drug-eluting stents, with a potential effect in preventing in-stent restenosis and thrombogenesis. In this paper, studies on pharmacological effects and mechanisms of extracts and main chemical constituents from E'Zhu in preventing vascular restenosis were summarized.
Animals ; Constriction, Pathologic ; drug therapy ; prevention & control ; surgery ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Endothelium, Vascular ; drug effects ; Humans ; Stents

There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.
Alkaloids ; chemistry ; pharmacology ; Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Zanthoxylum ; chemistry

This work reports the properties of dextran-spermine polycation (DSP) as a gene vector and its gene transfection efficiency in vitro. Oxidized dextran was reacted by reductive amination with spermine to obtain DSP, the resulted polycation was then incubated with plasmid pEGFP to form polyplexes by electrostatic interactions. DSP formed stable polyplexes when the weight ratio (DSP/DNA) varied from 4 : 1 to 20 : 1. The particle size and zeta potential of polyplexes were in the range of 162.6 - 187.9 nm and increased from + 8.45 mV to + 39.6 mV, respectively. DSP could effectively protect condensed DNA from DNase I degradation, and it showed strong buffering capacity in a certain pH range. The highest yields of transfection efficiency were found to be as high as Lipofectamine 2000 when the polyplexes were transfected to SMMC-7721 and BHK-21 cells at the weight ratio of 8 : 1. This research indicates that dextran-spermine polycation is a highly active gene vector in vitro.
Animals ; Cell Survival ; Cricetinae ; DNA ; administration & dosage ; Dextrans ; administration & dosage ; Genetic Vectors ; Spermine ; administration & dosage ; Transfection ; methods

The antitussive activity assay for the root extraction of Disporum cantoniense was carried out with coughing mice induced by ammonia liquor. The results showed that the ethanol and water extractions of D. cantoniense possess strong antitussive activity, and the high dose of the former was better than positive control, and then the constituents of the ethanol extraction were separated and purified by various modern chromatographic techniques. Their structures were identified by physico-chemical properties and spectroscopic data. As a result, eight compounds were isolated and identified as stigmast-4-en-3-one(1), (22E, 24R)-ergosta-5, 7, 22-trien-3beta-ol(2), obtucarbamate A(3), obtucarbamate B(4), neotigogenin(5), azo-2, 2'-bis[Z-(2,3-dihydroxy-4-methyl-5-methoxy) phenyl ethylene] (6),dimethyl {[carbonylbis (azanediyl)] bis( 2-methyl-5, 1-phenylene) j dicarbamate (7) , and quercetin-3-O-pB-D-glucopyranoside(8). All compounds were isolated from this plant for the first time, and the result of bioactivity-directed isolation showed that compounds 3, 4, and 6 had obvious effect on antitussive activity, and compound 6 had the same level as positive control.
Animals ; Antitussive Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Liliaceae ; chemistry ; Male ; Mice

Objective To investigate the correlation of heme oxygenase-1 (HO-1) expression and autophagy in mice with liver ischemia reperfusion (IR) injury,and to study the influence of HO-1 on the hepatic function.Methods Control group,IR group,Hemin + IR group and Znpp + IR group were constructed.Mice in the Hemin + IR group and the Znpp + IR group were pretreated by Hemin (HO-1 inducer) and Znpp (HO-1 inhibitor) before IR.According to different reperfusion time,the IR group was divided into the 0,2,6,12,24,48 and 72 hours groups,and the Hemin + IR group and the Znpp + IR group were divided into the 0,2,6,12,24 hours groups.The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected to evaluate the hepatic function.The autophagosome and pathological changes of liver were observed under electron microscope and hematoxylin and eosin (HE) staining,respectively.The expressions of HO-1 and autophagyassociated protein (LC3Ⅱ) in the protein level were detected by Western blot.All data were analyzed using the analysis of variance,t test and q test,respectively.Results The levels of ALT and AST of the IR group,Hemin + IR group and Znpp + IR group were significantly higher than those of the control group (F =96.17,85.53,P ＜0.05).The levels of ALT and AST of the IR 12 hours group and 24 hours group were significantly higher than those of the Hemin + IR 12 hours group and 24 hours group (qALT=--14.46,-7.85 ; qAST=-12.98,-5.26,P ＜0.05),but significantly lower than those of the Znpp + IR 12 hours group and 24 hours group (qALT=4.25,4.94;qAST=4.98,3.53,P ＜ 0.05).The results of HE staining showed that hepatic IR injury was significalty alleviated in the Hemin + IR group when compared with the IR group and the Znpp + IR group.The Suzuki degrees of hepatic IR injury in the control group,IR 12 hours group,Hemin + IR 12 hours group and the Znpp + IR 12 hours group were 0.5 ± 0.3,2.6 ± 0.5,1.1 ± 0.3,3.0 ± 0.4,respectively,with significant differences among the 4 groups (F =53.62,P ＜0.05).There were significant difference in the Suzuki degrees of hepatic IR injury between the IR 12 hours group and the Hemin + IR 12 hours group,and between the IR 12 hours group and the Znpp + IR 12 hours group (q =10.67,14.02,P ＜ 0.05).The results of electron microscopy showed that the number of autophagosome in the IR group was greater than the control group and Znpp + IR group,but lesser than the Hemin + IR group.The numbers of autophagosome in every 10 high power fields of the control group,IR 12 hours group,Hemin + IR 12 hours group and the Znpp + IR 12 hours group were 0.4 ±0.2,1.8 ±0.6,4.0 ± 1.8,0.7 ±0.5,respectively,with significant difference among the 4 groups (F =21.35,P ＜ 0.05).There were significant differences in the number of autophagosome between the IR 12 hours group and the Hemin + IR 12 hours group,and between the IR 12 hours group and the Znpp + IR 12 hours group (q =6.05,-3.03,P ＜ 0.05).The expressions of HO-1 and LC3Ⅱ in the IR group and the Hemin + IR group were significantly increased.The relative expressions of HO-1 protein in the Hemin + IR 6 hours group and the 12 hours group were 0.64 ±0.17 and 0.51 ±0.12,which were significantly higher than 0.45 ± 0.08 and 0.17 ± 0.03 of the IR 6 hours group and 12 hours group (t =4.03,4.69,P ＜ 0.05).The relative expressions of LC3Ⅱ protein in the Hemin + IR 6 hours group and the 12 hours group were 1.04 ± 0.20 and 1.20 ± 0.23,which were significantly higher than 0.58 ± 0.04 and 0.95 ±0.14 of the IR 6 hours group and 12 hours group (t =4.29,6.69,P＜0.05).The relative expressions of HO-1 protein in the Znpp + IR 6 hours group and 12 hours group were 0.23 ± 0.03,0.14 ± 0.02,respectively,and the relative expressions of LC3Ⅱ protein were 0.35 ± 0.04 and 0.49 ± 0.14,which were significantly lower than the HO-1 and LC3Ⅱ protein expressions in the IR 6 hours group and 12 hours group (tHO-1 =13.82,7.04; tLC3Ⅱ =7.21,4.03,P ＜0.05).Conclusion HO-1 is positively related to the amelioration of hepatic function,and it may be achieved by induction of autophagy.

A novel Aspergillus terreus strain M11 was isolated from the compost containing cellulose and identified. The isolate grow best at 45℃ and pH2.0. It was found that the activity of the CMCase was up to 3.680IU/mL with high heat stability and the optimal reaction conditions of the CMCase were at 60℃ and pH2.0.