Three butylphthalide derivatives were isolated from the Rhizome of Ligusticum chuanxiong using a series of isolation and purification approaches including macroporous resin, ODS-A column, Sephadex LH-20 and preparative HPLC. These structures were elucidated based on extensive spectroscopic data (UV, IR, HR-ESI-MS and NMR) and identified as (3Z,3aE)-(6R,7R,2'S)-6-hydroxy-7-(2-carboxyl-2-hydroxyethylthio)-3-(2-hydroxybutylidene)-4,5,6,7-tetrahydro-phthalide (1), (3Z,3aZ)-3-butylidene-6,7-dihydroxy-4,5,6,7-tetrahydro-phthalide 7-O-α-D-glucopyranosyl-(1→2)-β-D-fructo-furanoside (2) and 3-(3-β-D-glucopyranosyloxy-butylidene)-7-hydroxy-phthalide (3).

Objective To explore the effect of fluoride and arsenic pollution on bone metabolism in exposed population. Methods One hundred and fifty-two fluoride and arsenic exposed people were selected from Jiaole village, Yuzhang town, Xingron county, Guizhou province in 2006, and 59 not exposed people from Daguoduo village 13 km away from Jiaole village were selected as control. Urinary fluorine(UF), urinary arsenic (UAs), urinary hydroxyproline (UHYP), cross-linked N-telopeptides of type I collagen (UNTX) and bone strength index(STI) were detected. Results The main effect of fluoride on UHYP and UNTX were statistically significant (F = 9.785, 4.225, P < 0.01 ), but was not significant on STI(F = 0.183, P > 0.05). The main effect of arsenic on UNTX was statistically significant (F = 2.660, P < 0.05 ), but was not significant on UHYP and STI(F = 2.012, 0.183,all P > 0.05). The interaction between fluoride and arsenic on UNTX was statistically significant (F= 2.429, P <0.01), but was not significant on UHYP and STI(F= 1.218, 1.001, all P> 0.05). Conclusions Fluoride exposure can affect the metabolism of collagen and bone resorption, and Arsenic exposure main affect bone resorption, fluoride and arsenic co-exposure have more significant effect on bone resorption. UNTX may be used as biological biomarker of bone metabolism for population co-exposed to fluoride and arsenic in health monitoring.

To investigate the modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui with ussing chamber and rt-pcr, Rhodamine 123 (R123), a P-gp substrate and fluorescein sodium (CF), a model drug of non-P-gp substrate transported by a passive diffusion were taken as investigational drugs. Because these two drugs can be easily assayed and widely used in various research fields. The permeability of R123 or CF via Wistar rat jejunum membranes was evaluated by in vitro ussing chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Kansui for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry in the receiving solution. Meanwhile the expression of mdr1a in P-glycoprotein was detected by real-time fluorescent quantitative PCR. After oral administration of combined decoction of the single drug, the absorptive directed permeability of R123 increased significantly (P < 0.01). On the other hand, Kansui and combine decoction of the two drugs also decrease the permeability of secretory directed transport (P < 0.05). No action of Glycyrrhiza inflata was found on the secretory transport of R123 [Papp = (2.56 +/- 0.38) x 10(-5), cm x s(-1)] across the jejunum tissues, while Papp of control group was found [Papp = (2.35 +/- 0.27) x 10(-5), cm x s(-1)]. After oral administration of Kansui decoction for 1 week and 2 weeks, the levels of mdr1a expression in Wistar rats were lower than that of the control group, but there were no significant difference in the results. Meanwhile, Glycyrrhiza inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Kansui may slightly inhibit P-glycoprotein function in the intestinal membrane. For another, some compositions in Kansui inhibit P-glycoprotein function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-glycoprotein was enhanced by combination of Glycyrrhiza inflata and Kansui, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of Glycyrrhiza inflata and Kansui.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; pharmacokinetics ; Administration, Oral ; Animals ; Biological Transport ; drug effects ; Cell Membrane Permeability ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Euphorbia ; chemistry ; Fluorescein ; pharmacokinetics ; Glycyrrhiza ; chemistry ; Intestinal Absorption ; Intestinal Mucosa ; metabolism ; Jejunum ; metabolism ; Male ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Rhodamine 123 ; pharmacokinetics

OBJECTIVE To explore the antitumor effects of combined tanshinoneⅠ(TanⅠ),metformin (Met) and aspirin (Asp) on malignant melanoma in mice and the possible mechanisms. METHODS C57BL/6 mice were injected with 0.1 mL B16F10 cells(2.8×109L-1)to establish the subcutaneous trans-plantation tumor model at the right forelimbs axillary.Then,the mice were divided into 8 groups according to body mass,including model group, TanⅠgroup(20 mg·kg-1,ip),Asp group(210 mg·kg-1,orally in drinking water), Met group (70 mg·kg-1, orally in drinking water), Asp+Met group, TanⅠ+Asp group, TanⅠ+Met group and TanⅠ+Asp+Met group,10 mice in each group.Each mouse drank about 7 mL of water every day for a total of 18 d.The mouse body mass was measured every other day and the tumor diameter was calculated every day. The mice were sacrificed after treatment, the tumor mass was measured and the tumor inhibitory rates were counted. The histopathological changes of the liver and spleen were observed with HE staining. The percentage of lymphocytes in the tumor tissue such as CD8+T,CD4+T and Treg cells was detected by flow cytometry.Inflammatory factors such as interleukin-6 (IL-6),IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. RESULTS The body mass (including tumor mass)of mice in different groups increased during the experiment,but that of TanⅠ+Asp+Met group increased more slower than in model group(P<0.01).At the end of the experiment,no lesions were seen in any liver or spleen tissue by pathological observation,and the number of survivors was 8/10(model group),8/10(TanⅠgroup),7/10(Asp group),7/10(Met group),8/10(TanⅠ+Asp group), 8/10 (TanⅠ+Met group), 7/10 (Asp+Met group) and 5/10 (TanⅠ+Asp+ Met group), respectively. Compared with model group,there were no obvious changes in tumor volume or tumor mass in TanⅠ, Asp and Met groups and other two-two joint groups,but the tumor volume and tumor mass in TanⅠ+Asp+ Met group were significantly decreased (P<0.01, P<0.05), and the tumor inhibitory rate in this group was 46.2%.Compared with the model group,the percentage of CD8+T cells increased(P<0.05) in TanⅠ+Asp+Met group,but there were no significant changes in other groups.The contents of IL-6, IL-1β and TNF-α in tumor tissue of TanⅠ+Met group were much higher than in model group(P<0.01, P<0.05,P<0.05)and the content of IL-6 increased in TanⅠ+Asp+Met group(P<0.01).CONCLUSION Combination of TanⅠ,Asp and Met can effectively inhibit the growth of melanoma in mice,which may be related to the increasing percentage of CD8+T lymphocytes and IL-6 in tumor tissue.However there are possibly some side effects.

Background: Myocardial infarction (MI) is a major disease burden. Wild?type p53?induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. Methods:The study began in June 2014 and was completed in July 2016.We compared Wip1?knockout (Wip1?KO) mice and wild?type (WT) mice to determine changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5%isoflurane anesthesia.After MI, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin?6 (IL?6), tumor necrosis factor?α (TNF-α), and interleukin?1β (IL-1β) was assessed by quantitative real?time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor?stat3 (p?stat3) were also analyzed by Western blotting. Kaplan?Meier survival analysis, log?rank test, unpaired t?test, and one?way analysis of variance (ANOVA) were used for statistical analyses. Results: Wip1?KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac function before LAD ligation. After MI, Wip1?deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n = 35 [Wip1?KO], P < 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25 ± 0.36 vs. 5.84 ± 0.18, n = 10, P < 0.01, and 4 weeks: 6.05 ± 0.17 vs. 5.87 ± 0.24, n = 10, P > 0.05;cross?sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n = 6, P < 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ± 13.55, n = 6, P > 0.05), and reduced cardiac function (ejection fraction: 7 days: 29.37 ± 1.38 vs. 34.72 ± 1.81, P < 0.05, and 4 weeks: 19.06 ± 2.07 vs. 26.37 ± 2.95, P < 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P < 0.05, and 4 weeks: 8.79 ± 1.00 vs. 12.48 ± 1.48, P < 0.05; n = 10 [WT], n = 15 [Wip1?KO]). H&E staining revealed a larger infarct size in Wip1?KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P < 0.01). The expression of IL?6 and p?stat3 was downregulated in Wip1?KO mice (IL?6: 1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P < 0.01; and p?stat3/stat3: 1.15 ± 0.15 vs. 1.97 ± 0.23, n = 6, P < 0.05). Conclusion: The results suggest that Wip1 could protect the heart from MI?induced ischemic injury.

Resveratrol, isorhapontigenin and pinosylvin, isolated from Gnetum parvifolium, and their analogues have been synthesized and tested for their inhibitory activity of HIV-1. Natural product 12a and analogues (12d, 12e, 12g) display significant inhibitory activity of HIV-1 replication. Among them, compound 12d (trans-3, 4, 5, 4'-tetrahydroxystilbene) exhibits the most potent anti-HIV-1 activity with an IC50 value of 1.84 micromol x L(-1).
Anti-HIV Agents ; isolation & purification ; pharmacology ; Cells, Cultured ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gnetum ; chemistry ; HIV-1 ; drug effects ; physiology ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; cytology ; virology ; Molecular Structure ; Plants, Medicinal ; chemistry ; Stilbenes ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Virus Replication ; drug effects

OBJECTIVETo analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat.

METHODSExperiments were performed on 184 male Wistar rats (three exposure groups and a sham group). Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5, 5, and 10 mW/cm2. Learning and memory abilities were assessed by Morris water maze. High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus. Hippocampal structures were observed by histopathological analysis.

RESULTSFollowing long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d, 14 d, and 1 m in all three microwave exposure groups. Neurotransmitter concentrations of four amino acids (glutamate, aspartic acid, glycine, and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group. There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups. Further, mitochondria became swollen and cristae were disordered. The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles.

CONCLUSIONThese data suggest that the hippocampus can be injured by long-term microwave exposure, which might result in impairment of cognitive function due to neurotransmitter disruption.

Animals ; Chromatography, High Pressure Liquid ; Cognition ; Hippocampus ; pathology ; physiopathology ; radiation effects ; Learning ; Male ; Memory ; Microscopy, Electron, Transmission ; Microwaves ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB).

METHODSWe randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different

RESULTSAmong the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse

CONCLUSIONCombination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

Aged ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prospective Studies ; Prostatic Hyperplasia ; complications ; drug therapy ; Quinuclidines ; administration & dosage ; therapeutic use ; Solifenacin Succinate ; Sulfonamides ; administration & dosage ; therapeutic use ; Tetrahydroisoquinolines ; administration & dosage ; therapeutic use ; Urinary Bladder, Overactive ; complications ; drug therapy

OBJECTIVETo study the expressions of VEGF/VEGFRs and activation of STATs in ovarian epithelial carcinoma, and to elucidate direct effect of VEGF on ovarian carcinoma cells.

METHODSTissue samples from 42 women with primary ovarian epithelial carcinoma (OVCA), 29 with begnin ovarian tumor (OVBT) and 11 with normal ovarian tissue (NOV) were collected. LSAB immunohistochemical staining was used to determine the expression of VEGF, VEGFR1, VEGFR2 and activated STATS (P-STAT1, P-STAT3, P-STAT5, P-STAT6) proteins.

RESULTS(1) Semi-quantitative scoring showed that VEGF expression in OVCA was significantly higher than that in OVBT and NOV (P < 0.01). Expressions of VEGFR1 and VEGFR2 were significantly elevated in OVCA, including tumor cells and stromal vascular endothelial cells (P < 0.01, compared with OVBT and NOV). There was no difference in VEGFRs expressions between OVBT and NOV. (2) In OVCA, tumor cells and endothelial cells expressed P-STAT3 and P-STAT5 at significantly higher levels than those in OVBT and NOV (P = 0.000). The staining of P-STAT1 and P-STAT6 was weak with no significant differences among OVCA, OVBT and NOV. (3) Expressions of VEGFR1 and VEGFR2 in endothelial cells were significantly correlated with P-STAT5 and P-STAT3, respectively (P = 0.006 and 0.001). In cancer cells, VEGF, VEGFR1 and VEGFR2 were all significantly correlated with P-STAT3 and P-STAT5 (P = 0.000), but not with P-STAT1 or P-STAT6.

CONCLUSIONVEGF affects ovarian carcinoma cells via VEGFRs, and STATs probably participate in intracellular signaling of VEGF.

Adult ; Aged ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Endothelial Cells ; metabolism ; Female ; Humans ; Middle Aged ; Milk Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Ovary ; metabolism ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Signal Transduction ; Trans-Activators ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo evaluate the prognostic factors in treating primary liver cancer (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus providing evidence and optimizing Pi-strengthening and qi-regulating program.

METHODSClinical data of 151 PLC patients treated by PSQRM at Oncology Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was determined to analyze possible prognostic factors. Selected key factors were introduced into the COX proportional hazard model, and multivariate analysis was carried out.

RESULTSThe 1-year survival rate was 21.85%, the median survival time was 6.80 months, and the mean survival time was 8.98 months. The univariate analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin classification, albumin classification, Child-Pugh classification, and domestic staging of liver cancer were significant prognostic factors (P < 0.05). The statistic data of multivariate analysis indicated that CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer were independent factors influencing prognosis (P < 0.05).

CONCLUSIONThe prognosis of PLC treated with PSQRM is determined by multiple factors including CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; epidemiology ; therapy ; Female ; Humans ; Liver Neoplasms ; epidemiology ; therapy ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome