Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis / 中国天然药物

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg

Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS / 中国中药杂志

In this study,a method using ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) was established to identify complicated chemical constituents of Wikstroemia indica. Chromatographic separation was performed on an AcclaimTMRSLC 120-C18 column( 2. 1 mm×100 mm,2. 2 μm) using gradient elution with 0. 2% ammonium formate buffer salt solution( A)-0. 2% ammonium formate buffer salt solution methanol( B) as mobile phase. The column temperature was maintained at 30 ℃. The analytes were determined by positive and negative ion modes with electro-spray ionization source. A total of 52 compounds( including eleven coumarins,thirteen flavonoids,ten lignans,two amides,four phenolic acids,six sesquiterpenes and six other compounds) were identified or tentatively characterized from the water extract of W. indica by comparing their retention times and MS spectra with those of authentic standards or literature datas. Three compounds were found for the first time from W.indica namely isomer of indicanone,β-hydroxypropiovanillone and epiprocurcumenol. Furthermore,the fragmentation rules of some compounds were speculated and summarized. In addition,the cleavage pathways of guaiane sesquiterpenes were described for the first time,which can provide reference for studying the fragmentation pathways of similar compounds. This study provides an easy way to identify chemical constituents of traditional Chinese medicine and a basis for the further study on chemical fundamentals of W. indica.

Mechanism research of curcumin on cancer cells based on cell metabolic profiling / 中国中药杂志

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

Control of imported mosquito-borne diseases under the Belt and Road Ini-tiative / 中国血吸虫病防治杂志

Mosquito is a vector of many infectious diseases,and it is recognized a leading killer of human in the world.After the Belt and Road Initiative launches,more are countries involved and the international communication and cooperation are sig-nificantly growing in China.Therefore,the risk of imported infectious diseases is increasing as well,some mosquito-borne dis-eases which have been well controlled or seldom seen in China,will be more risky to cause locally transmission from imported cases and become the threat to people's health in China.This paper reviews the risk of major imported mosquito borne-diseases to China,and discusses the control strategy as well,so as to provide the suggestion for entry-exit inspection and control of im-ported mosquito-borne diseases in China.

Simultaneous determination of four flavonoids in Wikstroemia indica by HPLC / 中国中药杂志

The HPLC method was established to simultaneously determine the contents of myricetin, luteolin, apigenin and kaempferol in Wikstroemia indica ( L. ) C. A. Mey. The method was carried out on a Diamonsil C18 column (4. 6 mm x 250 mm, 5 µm) eluted with the mobile phases of water containing 0.15% phosphoric acid and acetonitrile in gradient mode. The UV detection wavelength was 365 nm. The flow rate was 1.0 mL · min(-1) and the column temperature was set at 30 °C. All the standard compounds showed a good linearity in the range of 0.100 8-1.008 (r = 0.999 2), 0.484 8-4.848 (r = 0.999 0) , 1. 354-13. 54 (r = 0.999 6), 0.316 8-3.168 mg · L(-1) (r = 0.999 0) for myricetin, luteolin, apigenin and kaempferol, respectively. The average recoveries of these four flavonoids were 98.5%, 100.9%, 99.7% and 98.9% with RSD 1.2%, 1.7%, 0.81% and 1.6%, respectively. In conclusion, the method is simple, rapid and accurate. It can be applied for the quality control of Wikstroemia indica.

Determination of the interaction kinetics between meloxicam and β-cyclodextrin using the quantitative high-performance affinity chromatography coupled with mass spectrometry / 药学学报

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.

Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice / 中国天然药物

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.

Release kinetics of single pellets and the multi-pellet system of tamsulosin hydrochloride sustained release pellets / 药学学报

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.

An oligopeptide improves solubility of paclitaxel by non-covalent interaction / 药学学报

Based on the principle of non-covalent interactions between oligopeptides and paclitaxel for improving the solubility of paclitaxel, an oligopeptide, N terminal-W(L)-FFGREKD-C terminal (W8), was designed and the solubilization effect of W8 on paclitaxel was detected through experiments. The binding efficiency and the possible optimal conformation were optimized by molecular docking program. The solubilization effect of W8 on paclitaxel was determined by RP-HPLC. And the solubilization mechanism of oligopeptide to paclitaxel was proposed at molecular level. It was indicated from the docking result that there existed pi-pi interactions and several hydrogen-bond interactions between the oligopeptide and paclitaxel. After being solubilized by the oligopeptide, the aqueous solubility of paclitaxel was increased to 28 times. This study provided basis for further research of the solubilization of paclitaxel by oligopeptide and confirmed a novel approach for the design of safe oligopeptide solubilizing excipient.

Research progress on intracellular metabolites based on metabolomics / 药学学报

Being an essential component of systematic biology, metabolomics has received attention in recent years. It is a post genomic technology aimed at qualitative and quantitative analysis of all low molecular-mass metabolites present in complex biological samples, and mainly investigates the change of endogenous metabolites of a stimulated or disturbed biological system. Investigations into intracellular endogenous metabolites in metabolomics have great advancement in recent years. This review outlines the progress of metabolomics in cell culture analysis including sample preprocessing methods and metabolite target analysis, metabolic profiling analysis, metabolomics analysis and metabolic footprinting analysis.

Simultaneous determination of five nucleosides and nucleobases of Rehmannia glutinosa Libosch. by high performance liquid chromatography / 药学学报

This study is to establish a method for simultaneously determination of five nucleosides and nucleobases, including hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. which was collected from different regions in China. A Diamonsil C18 column (250 mm x 4.6 mm, 5 microm) was used. Acetonitrile and 0.04 mol L(-1) potassium dihydrogen phosphate solution were adopted as mobile phase with gradient elution. The flow rate was 1 mL min(-1) and column temperature was 30 degrees C. The detection wavelength was at 254 nm. The method had good linearity over the range of 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8), 5.0 - 80.0 microg mL(-1) (r2 = 0.999 8), 1.0 - 16.0 microg mL(-1) (r2 = 0.999 5), 1.25 - 20.0 microg mL(-1) (r2 = 0.999 8) and 1.0 - 16.0 microg mL(-1) (r2 = 0.999 8) for hypoxanthine, uridine, adenine, guanosine and adenosine, respectively. The average recoveries were between 98.8% and 100.7%. The content of hypoxanthine, uridine, adenine, guanosine and adenosine in Rehmannia glutinosa Libosch. from different regions was significantly different. This established method was sensitive and reliable for the quantification of five chemical constituents in Rehmannia glutinosa Libosch.

Progress of the hydrokinetic chromatography and its application in the characterization of particulate drug delivery systems / 药学学报

In the present paper, the basic principles, the device and the analytical method of the hydrodynamic chromatography (HDC) were summarized, which is most widely used in hydrokinetic chromatography. The application of the hydrodynamic chromatography in the determination of the particle size and size distribution of the particulate drug delivery system was also reviewed. The method can determine the particle size of nano- and micron-scale particulate drug delivery systems rapidly. And this method also has the advantages of economic, convenient and no damage to the samples. In summary, there will be a good prospect for the application of HDC in the determination of particle size distribution features of particulate drug delivery systems.

In vivo effect of annexin I down-regulation on the growth of human pancreatic cancer in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To further explore the effect of annexin I on the tumor growth of human pancreatic cancer in nude mice.</p><p><b>METHODS</b>To knock down the expression of annexin I in pancreatic carcinoma cells by RNAi. A nude mouse model of human pancreatic cancer was established by subcutaneous inoculation of human pancreatic cancer cell line Suit-II cells. The effect of annexin I on tumor growth was assessed by tumor growth curve and tumor weight records, and Westen blot and flow cytometry were used to examine the expression of annexin I after annexin I-knocking down.</p><p><b>RESULTS</b>The results of Western blot revealed that the expression of annexin I was significantly decreased in Suit-II cells transfected with pSilencer-annexin I-siRNA1, and almost completely inhibited in the cells transfected with pSilencer-annexin I-siRNA2 and pSilencer-annexin I-siRNA3. The growth of tumors transfected with annexin I-siRNA2 and annexin I-siRNA3 was inhibited by 76.6% and 68.4%, respectively, in comparison with that of tumor from the parent Suit-II cells. At 44 days after tumor cell inoculation, the tumor weight was 0.8987 g (transfected with annexin I-siRNA2) and 0.8992 g (transfected with annexin I-siRNA3), significantly lower (P < 0.001) than that of tumor from parent Suit-II cells (2.5866 g) and transfected with annexin I-siRNAN (2.4070 g).</p><p><b>CONCLUSION</b>annexin I promotes the growth and proliferation of pancreatic carcinoma cells in vivo and increases the ability of tumor formation in nude mice. The results of this study support that annexin I may become a potential target in gene therapy for this disease.</p>

Tissue distribution and excretion of 5-fluorouracil from indomethacin 5-fluorouracil-1-ylmethylester in rats / 药学学报

To study the tissue distribution and excretion of indomethacin 5-fluorouracil-1-ylmethyl ester (IFM) metabolite 5-fluorouracil in rats, an accurate and specific high performance liquid chromatography method for quantifying IFM in rat plasma and tissues was developed. Biological samples were prepared by liquid-liquid extraction and separated on a Diamonsil C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase for tissue samples, plasma samples and feces samples were composed of methanol-water-36% acetic acid (3:96.9:0.1, v/v) and the mobile phase for urine samples was a mixture of methanol-water-36% acetic acid (10:89.9:0.1, v/v). The eluate was monitored by UV absorbance at 260 nm. After a single ig dose of 100 mg x kg(-1) IFM in rats, 5-Fu was mainly distributed in stomach, small intestine, and liver. The concentrations of 5-fluorouracil in other tissues and plasma were low. The excretion of 5-Fu in urine and feces amounted to 0.0065% and 0.063% of the dose, respectively. The method is shown to be accurate and specific, and suitable for preclinical pharmacokinetic studies of IFM.

Effective of ginkgolides on expression of apoptosis related gene during PC12 cells glucose deprivation / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of ginkgolides on glucose deprivation-induced apoptosis in PC12 cells and the mechanism underlying the protective effect.</p><p><b>METHOD</b>PC12 cells were treated under glucose deprivation, and the proliferation was determined by tetrazolium (MTT) assay. Furthermore, the mRNA levels of Bcl-2, Bax, c-myc were measured by Fluorescence Quantitative PCR (FQ-PCR).</p><p><b>RESULT</b>Ginkgolides could markedly inhibit the injury of glucose deprivation on the PC12 cells and increase the cell proliferation compared with the model groups (P <0.01). Ginkgolides could up-regulate Bcl-2 and down-regulate Bax and c-myc at 12 h, respectively. There were no significant differences in the Bcl-2 and Bax levels in both groups at 24 h, and ginkgolides only reduced the elevation of c-myc from 4. 32-fold to 2. 87-fold at this time.</p><p><b>CONCLUSION</b>Ginkgolides are able to protect the injured PC12 cells against cell apoptosis. During the early period of glucose deprivation, Bcl-2, Bax and c-myc were regulated to inhibit cell apoptosis by ginkgolides. After that, ginkgolides seems inhibit the apoptosis through attenuating the elevation of c-myc.</p>

Epidemiologic study on the relationship between smoking and sleep apnea/hypopnea syndrome / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate how smoking was affecting the prevalence of sleep apnea/ hypopnea syndrome (SAHS) among adults aged over 30 years in Chengde city of Hebei province.</p><p><b>METHODS</b>1168 subjects, over 30 years of age were derived from a random sample from a community-based population in Shuangqiao district of Chengde city. All subjects responded to a questionnaire at their own houses regarding their habits of snoring and smoking. 1168 subjects (95.2%) answered the questions satisfactorily.</p><p><b>RESULTS</b>(1) Among the smoking groups, the prevalence of snoring was 69.09%, higher than that in the nonsmoking groups 45.07% (P = 0.000). (2) In males, the smoking group had a higher prevalence (69.72%) of snoring than in the nonsmoking group (60.80%, P = 0.033). (3) Females in the smoking group had a higher prevalence of snoring (61.80%) than in the nonsmoking group (39.70%, P = 0.011). (4) The prevalence of snoring in males (60.80%) was significantly higher than that in females (39.70%, P = 0.000). (5) The prevalence (69.72%) of snoring in smoking males was similar to that in smoking females (61.80%, P = 0.336). (6) Data from logistic regression analysis indicated that smoking was one of the factors affecting snoring. (7) According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated. According to the AHI > or = 5 and the ESS > or = 9 cutoff-points, the prevalence rates of SAHS in smoking groups were both significantly higher than that in nonsmoking groups (P < 0.001).</p><p><b>CONCLUSION</b>Smoking and snoring among adults aged over 30 years had correlation in our city.</p>

Evaluation on the visual inspection with Lugol's iodine in cervical cancer screening program / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate visual inspection with Lugol's iodine (VILI) in cervical cancer screening program and to provide evidence for designing a cervical cancer screening algorithm in high risk areas of existing low-resource settings to reduce the incidence and mortality of cervical cancer.</p><p><b>METHODS</b>Women in Yangcheng county, Shanxi province were screened with VILI, colposcopy, liquid-based cytology test and human papilloma virus (HPV) DNA test. The efficacy of different screening tests was compared by Youden's index based on the pathology as the gold standard.</p><p><b>RESULTS</b>In the population being screened, the mean age was 40.80 +/- 10.75 years old. Based on pathological findings, 4.35% (32/735) of the subjects had >or= CIN (cervical intraepithelial neoplasia) II. The sensitivity and specificity for the VILI test (>or= positive) were 53.13 and 82.19, while 56.25 and 79.09 were for colposcopy (>or= low grade dysplasia) respectively. Comparing by the Youden's indexs, there was no statistically significant difference (P > 0.05) between VILI and colposcopy. However, statistical significant difference (P < 0.05) was found between VILI and liquid-based cytology test and HPV DNA test. In addition, there was no statistically significant difference (P > 0.05) found between the experienced doctors and the newly-trained doctors working in the field station.</p><p><b>CONCLUSION</b>With low sensitivity when using microscope but low cost of equipments, VILI can be one of the primary screening tests in China's rural area with low-resource settings if the screening frequency is to be increased.</p>

Tyrosine kinase dependent lectin-like oxidized LDL receptor-1 upregulation by thrombin and factor Xa in vascular smooth muscle cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>Thrombin and factor Xa are key players in the process of arterial thrombi formation and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a cell surface endocytosis receptor for atherogenic oxidized LDL (ox-LDL). Here we investigate whether thrombin and factor Xa can induce LOX-1 protein expressions in cell-associated forms and soluble forms in cultured bovine aortic smooth muscle cells (BSMCs).</p><p><b>METHODS</b>BSMCs were treated with thrombin or factor Xa in the presence or absence of AG1478, an epidermal growth factor (EGF) receptor-associated tyrosine kinase inhibitor. Total cell lysates and concentrated culture medium were then analyzed by Western blot using a mouse anti-LOX-1 monoclonal antibody.</p><p><b>RESULTS</b>LOX-1 protein levels in cell lysates and culture medium were significantly increased by thrombin and factor Xa in a concentration- and time-dependent manner. Upregulation of LOX-1 protein expressions in cell lysates and concentrated culture medium was observed at concentrations above 2.0 and 3.0 U/ml of thrombin and 50 and 100 nmol/L of factor Xa, respectively. Increased LOX-1 protein expressions in cell lysates and cell culture medium were detectable as early as 4 h and peaked at 12 h after treatment with thrombin or factor Xa. LOX-1 expression induced by thrombin and factor Xa could be blocked by pretreatment with AG1478.</p><p><b>CONCLUSIONS</b>Thrombin and factor Xa can act as LOX-1 inducers via tyrosine kinase activation.</p>

Primary study on the anti-tumor effect of ethanol extracts of Solanum lyratum / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the anti-tumor activity of the ethanol extracts of Solanun lyratum in vitro and in vivo.</p><p><b>METHOD</b>In vitro, the inhibitory effects of ethanol extracts of S. lyratum on proliferation of human hepatoma BEL-7402 cell and gastric carcinoma SGC-7901 cell were measured by MTT colorimetric assay. The mouse tumor model was used to investigate the effects of ethanol extracts on tumor growth.</p><p><b>RESULT</b>The studies demonstrated that ethanol extracts of S. lyratum inhibited proliferation of BEL-7402 cells and SGC-7901 cells, and the IC50 values on them were (287.40 +/- 5.84) micron x mL(-1) and (176.14 +/- 5.18) microg x mL(-1), respectively. The tumor inhibitory rate of high doses of ethanol extracts on S180 sarcoma-transplanted mice and H22 hepatic cancer were (41.15 +/- 4.54) % and (45.00 +/- 7.37) %, respectively. When the dose of ethanol extracts varied from low to high, it was able to inhibit the growth of S180 sarcoma-transplanted mice and H22 hepatic cancer in a dose-dependent manner.</p><p><b>CONCLUSION</b>In tumor inhibitory test, it was shown that the ethanol extracts of S. lyratum may possess significantly inhibitory effect in vitro and in vivo. No acute toxic effect was found in our experiment.</p>

Expression of major histocompatibility complex in ovarian epithelial carcinoma / 肿瘤研究与临床

Objective To investigate the numbers and the expression of MHC-Ⅰpositive cells in hu- man ovarian epithelial carcinoma tissues and provide the experimental data in the futher biological therapy of ovarian carcinoma.Methods Thirty one samples of ovarian epithelial carcinoma were analysed with flow cy- tometry for MHC classⅠexpression.Results The number of MHC classⅠcells(25.22?21.23,4.37?3.63)was fewer in ovarian epithelial carcinoma than that in normal ovarian tissues(43.56?18.47,7.43?5.87),and was related with pathologic grades(P