This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
Animals ; Antihypertensive Agents ; chemistry ; pharmacology ; Calcium Channel Blockers ; chemistry ; pharmacology ; Calcium Channels, L-Type ; genetics ; metabolism ; Drug Repositioning ; methods ; Molecular Structure ; Myocardium ; metabolism ; Rabbits

Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.
Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Calorimetry, Differential Scanning ; Drug Carriers ; Indomethacin ; administration & dosage ; chemistry ; Microscopy, Electron, Scanning ; Nanostructures ; Phosphodiesterase 3 Inhibitors ; administration & dosage ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Tetrazoles ; administration & dosage ; chemistry ; X-Ray Diffraction ; Zinc Oxide ; chemistry

Aim To explore the effect and mechanism of antioxidant peptide AOP1 on repair of skin burn wound healing in mice.Methods Fluorescence probe DCFH-DA was used to detect the changes of intracellular reactive oxygen species (ROS).Cell proliferation and migration assay were used to detect AOP1 toxicity and its effect on wound healing.Moreover,the skin scald wound was made on the shaved dorsum of the anesthetized mice with a 1.0 cm diameter brass cylinder heated in a water bath at 80 ℃ for 2 min and pressed against the rat skin for 10 s.The effects of AOP1 on the healing of skin burns were observed by HE and Masson staining and the contents of MDA and the activity of SOD in skin tissues were measured.Results The antioxidant peptide AOP1 could significantly reduce the number of ROS in HaCaT and L929 cells,and promote cell migration and proliferation.Compared with the untreated group,the skin healing time of AOP1 group was short,the healing rate was high,the area of scab was small,and inflammation and the content of MDA in burned tissue significantly decreased.The effect of AOP1 on healing of burn wound healing was also confirmed by HE and Masson staining.Conclusion It is suggested that the antioxidant peptide AOP1 with natural activity may promote the healing of skin burns by reducing the oxidative stress caused by burns.

OBJECTIVETo investigate the comprehensive measures for improving radical resection rate and safety of Bismuth-Corlette type III hilar cholangiocarcinoma.

METHODSThe clinical data of 15 patients with Bismuth-Corlette type III hilar cholangiocarcinoma who performed radical resection from June 2009 to December 2011 was analyzed retrospectively. There were 11 male and 4 female patients, aged from 45 to 74 years (mean 59 years). The preoperative evaluation were conducted by using magnetic resonance cholangiopancreatography (MRCP), dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System providing three-dimensional reconstruction of tumor, bile duct, hepatic artery and portal vein, which could help to chose the appropriate treatment modality. All patients were treated with selective hemi-hepatic vascular control of removal liver, hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy. The merits of each evaluation methods and measures of surgical treatment were analyzed thoroughly.

RESULTSThe preoperative evaluation modalities including the dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could clearly show the involvement of bile duct, hepatic artery and portal vein invaded by the tumor. The satisfactory postoperative recovery could be achieved by the remnant liver volume of > 40% after the hemi-hepatectomy combined with whole caudate lobe resection through the selective preoperative biliary drainage and hemihepatic vascular control. The mean complication was transient aggravated liver dysfunction. There was no death reported during perioperative period in the group.

CONCLUSIONSThe preoperative imaging evaluation modalities including MRCP, dual source spiral CT combined with IQQA-Liver CT Imaging Analysis System could do favor for the preoperative evaluation of invasion degree of hilar cholangiocarcinoma and the selection of appropriate surgical treatment. Hemi-hepatectomy combined with whole caudate lobe resection and regional lymphadenectomy could be an alternative management of Bismuth-Corlette type III hilar cholangiocarcinoma.

Aged ; Bile Duct Neoplasms ; surgery ; Cholangiocarcinoma ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVETo observe the effect of chronic lead contaminant on protein expression of protein kinase (PKC) and calmodulin (CaM) in hippocampus of baby-rats.

METHODSThe Wistar pregnant rats were randomly divided into 3 groups fed with distilled water and lead-contained water (0.2% and 1.0% lead acetate) respectively. The lead exposure period ranged from the 0 day of pregnancy to the offspring weaned. Then the baby-rats were fed with lead water the same as their mothers. Pups were killed at postnatal day 8 and 50 respectively. Atomic absorption spectrometry was used to determine lead content of rats' brain. Western-blotting was used to observe protein expression of PKC and CaM in hippocampus of baby-rats.

RESULTSThe brain lead content of test groups was much higher than that of the control group in the same growth period (P < 0.01). The content of brain lead in rats of postnatal day 50 was significantly higher than that of rats of postnatal day 8 (P < 0.01). Compared with control group, PKC and CaM protein expressions of chronic lead exposure baby-rats in the hippocampus were down trend (P < 0.05).

CONCLUSIONThe decrease of PKC and CaM protein expression level in hippocampus might be one of the molecular mechanisms of lead induced impairment of learning and memory.

Animals ; Calmodulin ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; Protein Kinase C ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo assess the value of color Doppler ultrasound in evaluating the mesenteric lymph nodes in healthy children.

METHODSThe mesenteric lymph nodes were examined with color Doppler ultrasonography for 730 randomly selected healthy children under 14 years of age, including 410 boys and 298 girls who did not report any recent medical conditions.

RESULTSAbdominal lymph node detection rate was higher in boys than in girls. Abdominal lymph nodes were detected most often in children between the ages of 1 and 4 years, and the lymph node size decreased gradually with age.

CONCLUSIONColor Doppler ultrasonography is valuable for evaluating abdominal lymph nodes in children.

Child ; Female ; Humans ; Lymph Nodes ; diagnostic imaging ; Male ; Mesentery ; diagnostic imaging ; Ultrasonography, Doppler, Color

OBJECTIVETo study the effect of p38 on the cycloheximide (CHX)-induced HL-60 cell death through mitochondria pathway.

METHODSInhibition of p38 pathway was by SB203580 (SB). Four groups were set up: control, SB only, CHX only and SB + CHX. Sub-diploid cell ratio was detected by PI staining flow cytometry at 6, 9, 12, 18, 24 h time points, and apoptotic cell ratio by Annexin V-FITC/PI double staining flow cytometry at 6 h and 18 h time points. High J-aggregate cells were evaluated by the J-aggregate contents, measurement of the J-aggregate (FL2) and J-monomer (FL1) by JC-1 flow cytometry, calculation of the delta psi m by FL2/FL1 and analysis of the delta psi m changes at 18 h time points.

RESULTSThe sub-diploid cell ratio in CHX group was significantly higher than that in control group at 6 h time point, and the ratio in SB + CHX group was significantly higher than that in CHX group at 9 h time point. At 18 h time point the apoptotic cell ratios in both CHX and SB + CHX groups were significantly higher than those in control group (P < 0.01). There was no significant difference of apoptotic cell ratio between CHX group and SB + CHX group (P > 0.05). At 18 h time point the necrotic cell ratios in both CHX and SB + CHX groups were significantly higher than that in control group (P < 0.01); and that in SB + CHX group was significantly higher than that in CHX group (P < 0.01). The high J-aggregate cell ratios in CHX and SB + CHX groups were significantly lower than that in control group (P < 0.05), and that was signficantly lower in SB + CHX group than in CHX group (P < 0.01). For the FL2/FL1 value (delta psi m) CHX group (0.17 +/- 0.01) and SB + CHX group (0.05 +/- 0.003) were significantly higher than control group (0.38 +/- 0.02) (P < 0.01), and SB + CHX group was significantly lower than CHX group (P < 0.01).

CONCLUSIONCHX can induce HL-60 cell apoptosis and the cell mitochondria depolarization, and the latter was intensified by inhibition of the p38 pathway. p38 pathway may related to the cell necrosis in the cycloheximide-induced HL-60 cell apoptosis model. s

Apoptosis ; drug effects ; Cycloheximide ; pharmacology ; HL-60 Cells ; Humans ; Membrane Potentials ; Mitochondria ; physiology ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVETo compare the enlarged mesenteric lymph nodes in healthy children with those children with mesenteric lymphadenitis.

METHODSAccording to the diagnostic criteria defining lymph node enlargement as a 5-mm enlargement or greater in the short diameter, 137 healthy children and 148 children with mesenteric lymphadenitis were retrospectively analyzed for mesenteric lymph node enlargement based on the ultrasonographic data.

RESULTSThe distribution of enlarged mesenteric lymph nodes was detected in the right lower quadrant (RLQ) in 46.3%, in the para-aortic areas in 19.2%, and in the left lower quadrant (LLQ) in 13.6% of the children. The clusters of lymph nodes between the two groups showed no significant difference in the distribution, age, L/W, longitudinal diameter or clusters, only the short diameter differed significantly between them.

CONCLUSIONEnlarged mesenteric lymph nodes are present in many healthy children, which does not necessarily suggests any abnormalities. The mesenteric lymph nodes increase with the age until 6 years and then decrease. The lymph nodes with a short diameter larger than 8 mm may indicate the condition of mesenteric lymphadenitis.

Abdomen ; Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Hypertrophy ; Lymph Nodes ; pathology ; Lymphatic Diseases ; diagnosis ; pathology ; Male ; Mesenteric Lymphadenitis ; diagnosis ; pathology ; Mesentery ; Retrospective Studies

Midkine is a heparin-binding growth factor, which plays important roles in the regulation of cell growth and differentiation. The non-tagged recombinant human midkine (rhMK) is therefore required to facilitate its functional studies of this important growth factor. In the present work, rhMK was expressed in Escherichia coli (E. coli) BL21 (DE3). The expression of midkine was efficiently induced by isopropyl-beta-D-thiogalactopyranoside (IPTG). After sonication, midkine was recovered in an insoluble form, and was dissolved in guanidine hydrochloride buffer. Renaturation of the denatured protein was carried out in the defined protein refolding buffer, and the refolded protein was purified using S-Sepharose ion-exchange chromatography. The final preparation of the rhMK was greater than 98% pure as measured by sodium dodecylsulfate-polyacrylamid gel electrophoresis (SDS-PAGE) and reverse phase high performance liquid chromatography (RP-HPLC). The purified rhMK enhanced the proliferation of NIH3T3 cells.
Animals ; Base Sequence ; Cell Proliferation ; drug effects ; Cytokines ; biosynthesis ; genetics ; isolation & purification ; pharmacology ; Escherichia coli ; genetics ; Humans ; Mice ; Molecular Sequence Data ; NIH 3T3 Cells ; Recombinant Proteins ; biosynthesis ; isolation & purification

Objective To explore the effects of gravitational traction and target regulation of caspase3 on the degenerative intervertebral disc cells in rabbits.Methods Rabbits nucleus pulposus cells transfected with caspase3 siRNA or negative control siRNA were incubated in serum-starved medium for 6 hours and 48 hours.The expression of caspase3 siRNA and cell apoptosis were analyzed by RT-qPCR and Annexin V-fluorescein staining.In order to create intervertebral disc degeneration model,the right anterior side of the annulus fibrosus of lumbar vertebrae of 35 rabbits were damaged by 16-gauge needle.After confirming the success of modeling,35 animal models were randomized into 3 groups:model group (n=10),negative siRNA group (n=10) and caspase3 siRNA group (n=5).Either negative control siRNA or caspase3 siRNA was injected into the center of nucleus pulposus using a 26-gauge needle from the left anterior side,while the model group received no injection.Nucleus pulposus tissue of 5 rabbits selected randomly from every group after 48 hours were analyzed by PCR and Western blotting for caspase3 mRNA and protein expressions.Half of the casepase3 siRNA group were selected randomly and received a routine gravitational traction using a model of our own design,30min per day for 2 weeks,while other groups received no treatment.TNF-o and IL-1β expression levels and histopathological observations were performed after intervention.Results Expression of caspase3 mRNA in rabbit nucleus pulposus cells transfected with caspase3 siRNA decreased obviously in serum-starved medium,and the apoptosis rate of cells cultured in serum-starved medium decreased significantly (P＜0.05).Caspase3 mRNA and caspase3 protein expression of nucleus pulposus injected by caspase3 siRNA down-regulated in the caspase3 siRNA group.Compared with model group and negative control siRNA group,TNF-α and IL-1β expression levels of caspase3 siRNA traction group decreased significantly (P＜0.05),but there was no statistical significance compared with caspase3 siRNA group (P＞0.05).Pathological observation revealed that viable cell number and extracellular matrix contents increased and collagenous fibers arranged regularly in caspase3 siRNA traction group.Conclusion Gravitational traction and target regulation of caspase3 can prevent apoptotic cell death and delay early intervertebral disc degeneration.