BACKGROUND:In order to overcome the shortcomings of single materials, antibiotics-loaded hydroxyapatite/titanium composites have attracted people’s attentions.
OBJECTIVE:To evaluate the biocompatibility of vancomycin/hydroxyapatite/titanium nanotubes.
METHODS:Mouse osteoblasts, MC-3T3-E1, were co-cultured with titanium (Cp-T), TiO2nanotubes, and vancomycin/hydroxyapatite/titanium nanotubes, respectively. Cel morphology and growth were observed after 1, 3 and 5 days of co-culture under inverted microscope and scanning electron microscope. The cel proliferation was detected by AO-EB method. The total protein, calcium and alkaline phosphatase levels were detected at 7 and 14 days of co-culture.
RESULTSAND CONCLUSION:The MC-3T3-E1 cels with good viability and morphology adhered wel on the surface of vancomycin/hydroxyapatite/titanium nanotubes compared with those on the surface of pure titanium and TiO2nanotubes under the scanning electron miscroscope. Moreover, there were a large amount of pseudopodia on the surface of composite nanotubes. Compared with the other two groups, the cel number on the surface and the levels of intracelular calcium and alkaline phosphatase were al higher in the vancomycin/hydroxyapatite/titanium nanotubes group. These findings suggest that the vancomycin/hydroxyapatite/titanium nanotubes have good biocompatibility and no cytotoxicity.

BACKGROUND: Present studies have proved that titanium coating nanotubes cannot only promote the biological activity of the material itself, but also be used as a drug carrier loading antibiotics and growth factors. OBJECTIVE: To investigate the antibacterial properties of vancomycin/hydroxyapatite/titanium dioxide nanotubes in vitro and in vivo. METHODS: The releasing property in vitro of vancomycin/hydroxyapatite/titanium dioxide nanotubes and vancomycin/titanium dioxide nanotubes were detected. And 1010/L Staphylococcus aureus dilution was put onto the commercial titanium, titanium dioxide nanotube and vancomycin/hydroxyapatite/titanium dioxide nanotube, respectively. Twenty-four hours later, the bacterial growth and activity was observed by scanning electron microscope and confocus scanning electron microscope, respectively. RESULTS AND CONCLUSION: Scanning electron microscope showed: the number of Staphylococcus aureus was the least on the vancomycin/hydroxyapatite/titanium dioxide nanotube, and the bacterial morphology was destroyed. Confocus scanning electron microscope observed: the number of bacteria and viable bacteria was the least on the vancomycin/hydroxyapatite/titanium dioxide nanotube, and the most on the commercial titanium. Besides, the releasing time of vancomycin from the hydroxyapatite/titaniumdioxide nanotube was up to 18 days, but the releasing time of vancomycin was only 4 hours from the titanium dioxide nanotube. In conclusion, the vancomycin/hydroxyapatite/titanium dioxide nanotube has good antibacterial property and slow-releasing performance.

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

AIMTo investigate the combined effect of cosolvent and cyclodextrin (CD) on solubilization of insoluble drugs.

METHODSPhase-solubility method was applied to determine solubilization of two diterpenoids in cosolvent / cyclodextrin combinations. The combined effect was evaluated and explained with an established mathematical model, and the model parameters were calculated by means of nonlinear regression analysis.

RESULTSThe strong agreement between the predicted and the observed solubility data supports the validity of the proposed model, with the determination coefficients of two regression models were 0.993 and 0.992, separately.

CONCLUSIONThe validated mathematical model can be used to explain and predict the combined solubilization of the two insoluble drugs in different cosolvent systems.

2-Hydroxypropyl-beta-cyclodextrin ; Algorithms ; Diterpenes ; chemistry ; Models, Chemical ; Solubility ; Solvents ; chemistry ; Water ; chemistry ; beta-Cyclodextrins ; chemistry

Cell Membrane Permeability ; Crystallization ; Dosage Forms ; Nephelometry and Turbidimetry ; Pharmaceutical Preparations ; chemistry ; Pharmacokinetics ; Quantitative Structure-Activity Relationship ; Solubility ; Technology, Pharmaceutical ; methods ; trends

Objective To investigate the effects of ginkgo flavone on the expression of NF-κB and TLR4 in the liver of mice with nonalcoholic fatty liver disease (NAFLD). Methods 120 KM mice were randomly divided into the control group, model group, as well as high, medium and low dosage of ginkgo flavone groups. The animal model of NAFLD in mice was constructed with high fat diet. The pathological changes of liver, liver index , the serum TNF-α, IL-6 , TG , NF-κB and TLR4 in hepatic tissue was observed after 8 weeks of administration. Results Compared with the model group, the level of liver index, serum TG, TNF-α, IL-6 and the expression of NF-κBp65 in the ginkgo flavone groups dramatically decreased 8 weeks after the administration. And the hepatic steatosis was milder. There was no statistical differences in the expression of TLR4 between the ginkgo flavone groups and the control group (P > 0.05). Conclusions These results suggested the closely relationship between TLR4/NF-κB inflammatory pathway and NAFLD. Ginkgo flavone had the therapeutical effects on NAFLD by anti-inflammatory and lipid-lowering action, but no effect was observed on the expression of TLR4 in hepatic tissue.

Animals ; Animals, Newborn ; Cerebral Cortex ; drug effects ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; Progesterone ; pharmacology ; Rats ; Rats, Sprague-Dawley

Objective In order to study the difference of depression-like behaviours among three widelyused stress models in rats.Methods The new-born Spragne-Dawley rats were randomly divided into maternal deprivation(MD) group(n=27),chronic mild stress(CMS) group (n=29),dual stress(DS) group ( n=31 ) and control (C) group ( n =30) on postnatal day 1.MD rats only received maternal deprivation.CMS rats only received chronic mild stress when 10 weeks old.DS rats received both maternal deprivation and chronic mild stress.Control rats received no experimental handling.Behavior tests including forced swimming test and sucrose consumption which were carried out to evaluate rats' depression-like behaviors in the thirteenth weeks.The extend time of floating and sucrose preference ratio should be recorded in the forced swimming test and sucrose consumption test respectively to reflect the behavior of helplessness and anhedonia of rats.Results In the forced swimming test,the extend floating time of MD group( 119.30 ± 65.56) s,CMS group ( 145.00 ± 80.24) s and DS group ( 170.03 ±61.75 )s were longer than the control group(81.14 ± 52.40)s (F =11.53,P ＜ 0.01 ).In the sucrose consumption test,the MD group(0.32 ± 0.22) had a low sucrose consumption.The comparison of the MD group and CMS group (0.43 ± 0.28 ) to the control group (0.54 ± 0.28 ) had significant differences (F =4.33,P ＜ 0.01 ).In these four groups,no sexual difference was found in the forced swimming test and sucrose consumption test ( all P ＞ 0.05 ).Conclusion The results suggest that MD,CMS and DS may induce some kind of depression-like behaviors in rodents such as anhedonia or the behavior of helplessness and the depression-like behaviors induced by different stresses are similar in male and female individuals.

Objective:To explore protective effect of atorvastatin on blood vessels in early stage of atherosclerosis (AS).Methods:A total of 120 patients without AS plaques,who had >2 cardiovascular risk factors and received control cardiovascular risk factors therapy,were randomly divided into four groups:control group (did not receive atorvastatin),atorvastatin 5mg group,10mg group and 20mg group (received corresponding dose of atorvastatin). All patients were followed up for six months,changes of thromboxane B2 (TXB2),6-Keto-prostaglandin F1α (6-Keto-PGF1α),brachial-ankle pulse wave velocity (baPWV),ankle brachial index (ABI)and intima-media thickness (IMT)were observed.Results:There were no significant changes in ABI and IMT between before and after treat-ment among four groups (P >0.05 all).Compared with baseline,TXB2、baPWV levels significantly rose,6-Keto-PGF1αlevel significantly decreased after treatment in control group and 5mg group;in contrast,TXB2、baPWV lev-els significantly decreased,6-Keto-PGF1αlevel significantly rose after treatment in 10mg group and 20mg group(P <0.05~ < 0.01).After treatment six-month,compared with control group and 5mg group,the TXB2 [(148.3 ± 29.2)pg/ml,(142.3±30.6)pg/ml vs.(111.5±22.8)pg/ml,(104.9 ± 17.4)pg/ml]、baPWV[(1621.1 ± 136.1) cm/s,(1597.7±125.3)cm/s vs.(1232.9±132.3)cm/s,(1178.2±155.1)cm/s]levels significantly decreased,6-Keto-PGF1α[(104.7±66.1)pg/ml,(102.2±70.3)pg/ml vs.(132.8±48.3)pg/ml,(139.1±66.3)pg/ml]level significantly rose(P <0.05~<0.01)in 10 mg group and 20 mg group.Conclusion:Atorvastatin has protective effect on blood vessels in early stage of atherosclerosis,and 10mg atorvastatin may be the minimum effective dosage to protect blood vessels.

Objective To study the effect of dual stress on the behaviors and the expression of hippocampal let-7a and serotonin receptor 4(HTR4) in rats.Methods Newborn SD rats were randomly divided into dual stress group (DS,n=6) and control group (C,n=6).The DS rats were deprived of the mother care 6 hours per day from postnatal day 1 to 14 and then were exposed to chronic mild stress for 21 days from 10 weeks old,while the rats from C group received no experimental handle but husbandry care.Open field test,forced swimmiug test and sucrose consumption test were conducted to evaluate rats' depression-like behaviors at the age of thirteen weeks.The let-7a level in hippocampus was detected by real-time Polymerase Chain Reaction and the HTR4 protein level was measured by Western Blotting.Results In the open filed test,the rearing times of DS rats was shorter than that of C group((7.50±2.35) vs (19.00±5.73),P＜0.05).In the forced swimming test,the floating time of DS rats was longer than that of C group ((110.17 ± 1.72)s vs (70.33± 1.16)s,P＜ 0.05).In the sucrose c onsumption test,DS rats consumed less sucrose than rats from C group did((0.80±0.73) vs (0.52±0.26),P＜ 0.05).The protein level of hippocampal HTR-4 in DS group was lower than that of C group((1.44±0.38) vs (0.46±0.29),P＜0.01).The let-7a level in DS group was higher than that of C group((0.04±0.01) vs (1.58±0.27),P＜0.01).The Pearson correlation analysis revealed that the sucrose preference rate of rats were negatively and positively correlated with hippocampal let-7a and HTR4 level respectively(r=-0.653,P＜0.05; r=0.774,P＜0.01),and hippocampal let-7a level showed negative association with HTR4 protein level (r=-0.803,P＜0.01).Conclusion Dual stress can induce the depressive behaviors of rats and affect the expression of let-7a and HTR4 in hippocampus.Hippocampal HTR4 and let-7a might be involved in determining individual ability to experience pleasure in rats;and hippocampal let-7a may be involved in the regulation of HTR4 gene expression in rats.