90,180 and 360 mg·kg-1 on general central nervous system (CNS) of mice was investigated by general behavior observation, nembu-tal subthreshold hypnosis experiment, spontaneous activity test and rotary rod test. The changes in blood pressure, heart rate, electro-cardiogram, breathing flow and frequency in anaesthetic Bealge dogs were observed to evaluate the effects of the capsules respectively at the low, medium and high dosage of 16,32 and 64 mg·kg-1 on cardiovascular and respiratory systems. Results:The general behavior of mice was normal after the administration of Sansheng Jindan capsules. The capsules showed no synergetic hypnotic effect on nembu-tal, and had no influence on the spontaneous activity and body coordination ability of mice (P>0. 05). The blood pressure, ECG and respiratory index of anaesthetic Bealge dogs were also normal after the administration of the capsules (P>0. 05). Conclusion:There are no significant effects of Sansheng Jindan capsules at the experimental dosages on central nervous system of mice and respiratory and cardiovascular systems of Beagle dogs.

This paper is to evaluate the biocompatibility and cytotoxicity of a new Ni-free Zr-based bulk metallic glass (BMG), Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, by comparing it with conventional Ti6Al4V alloy. According to ISO 10993-5: 1999 and GB/T 16886.5-1997 standards, Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, pure Zr and Ti6Al4V materials were extracted with surface area of sample/volume of medium ratio being 1 cm2/mL and 0.5 cm2/mL, respectively. The viabilities of MG-63 cells (Human osteosarcoma cell line) cultured in the BMG medium extracts for 1, 3 and 5 days were determined by CCK-8 assay. The cellular morphology of MG-63 cells cultured on the surface of samples for 3 days was tested through laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM). The relative growth rate (RGR) of MG-63 cells cultured in Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and pure Zr were both more than 85%, indicating that the cytotoxicity of BMG was relatively low and met the national biomedical material eligibility standard. There was insignificant difference in the morphology of MG-63 cells cultured in the BMG medium extracts and the control group through LSCM and SEM, which showed the BMG had excellent biological compatibility. The Zr-based bulk metallic glass Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and the conventional Ti6Al4V alloy both had no obvious cytotoxicity to MG-63 cells. These results provided evidence that the new Zr-based bulk metallic glass could be potential replacement material for the orthopedic surgical implant.
Alloys ; Biocompatible Materials ; Cell Line ; Glass ; Humans ; Microscopy, Electron, Scanning ; Nickel ; Titanium ; Zirconium

In this study, the rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS) was used to profile the metabolites of urine samples from chronic heart failure (CHF) patients and healthy controls to find the differential metabolites which could provide the scientific evidence to explain the pathogenesis of the disease and supply a better therapy plan.Urine samples from 15 CHF patients (age (62.27±3.14) years) and 15 healthy controls (age (65.41±4.63) years) were analyzed by RRLC-QTOF/MS.After processing the data, the multivariate statistical analysis (principal component analysis, PCA) was performed to find the potential biomarkers.Result showed that urine samples of CHF patients were successfully distinguished from those of healthy controls.Two significantly differentially expressed metabolites, uridine and alanyltryptophan, were found and identified as potential biomarkers.The result showed that the LC-MS based metabolomics approach had good performance to identify potential biomarkers, and the disorder of uracil metabolism and Tryptophan metabolism may play an important role in the mechanism of CHF.

OBJECTIVE: To help researchers learn and utilize drug target database for new drug research, and to provide important information for the management and construction of Drug Target Database.

OBJECTIVEIn this study, we aimed to investigate the expressions of adhesion molecules on human bronchial epithelial cells and neutrophils in co-culture system, assess the effects of puerarin on suppressing these adhesion molecules expressions, and explore the roles of two crucial signal-transduction elements p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NF-κB) in modulating adhesion molecules expressions.

METHODSNeutrophils and BEAS-2B cells (one human bronchial epithelial cell line) were co-cultured, and adhesion molecules expressions on cell surface were detected using flow cytometry. The mRNA levels of adhesion molecules were assessed by real-time quantitative polymerase chain reaction (real-time qPCR). Phosphorylated p38 MAPK and inhibitor κB were analyzed by Western blot.

RESULTSIn co-culture system, adhesion molecules expressions on BEAS-2B cells and neutrophils were enhanced significantly (P<0.05). Correspondingly, the mRNA levels of adhesion molecules were also increased greatly. Moreover, the pretreatment of peurarin obviously suppressed adhesion molecules expressions on cell surface. Furthermore, phosphorylated p38 MAPK and inhibitor κB in BEAS-2B cells and neutrophils were elevated in co-culture system, but decreased significantly after upon the treatment of peurarin (P<0.05).

CONCLUSIONSCoculture boosted the interactions between human bronchial epithelial cells and neutrophils mimicking airway inflflammation, whereas peurarin decreased the expression of adhesion molecules on cell surface by suppressing the activities of p38 MAPK and NF-κB pathways, and exhibiting its anti-inflflammation activity.

Animals ; Base Sequence ; Bronchi ; cytology ; enzymology ; metabolism ; Cattle ; Cell Adhesion Molecules ; metabolism ; Cell Line ; Coculture Techniques ; DNA Primers ; Down-Regulation ; drug effects ; Epithelial Cells ; enzymology ; metabolism ; Isoflavones ; pharmacology ; NF-kappa B ; metabolism ; Neutrophils ; enzymology ; metabolism ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.

OBJECTIVETo investigate the effects of two fluid resuscitations on the bacterial translocation and the inflammatory factors of small intestine in rats with hemorrhagic shock.

METHODSFifty SD healthy male rats were randomly divided into 5 groups (n equal to 10 per group): Group A (Sham group), Group B (Ringer's solution for 1 h), Group C (Ringer's solution for 24 h), Group D (hydroxyethyl starch for 1 h) and Group E ((hydroxyethyl starch for 24 h). A model of rats with hemorrhagic shock was established. The bacterial translocation in liver, content of tumor necrosis factor-alpha (TNF-alpha) and changes of myeloperoxidase enzyme (MPO) activities in small intestine were pathologically investigated after these two fluid resuscitations, respectively.

RESULTSThe bacterial translocation and the expression of TNF-alpha in the small intestine were detected at 1 h and 24 h after fluid resuscitation. There were significant increase in the number of translocated bacteria, TNF-alpha and MPO activities in Group C compared with Group B, significant decrease in Group E compared with Group D and in Group B compared with Group D. The number of translocated bacteria and TNF-alpha expression significantly decreased in Group E as compared with Group C.

CONCLUSIONSThe bacterial translocation and the expression of TNF-alpha in the small intestine exist 24 h after fluid resuscitation. 6% hydroxyethyl starch can improve the intestinal mucosa barrier function better than the Ringer's solution.

Animals ; Bacterial Translocation ; drug effects ; Fluid Therapy ; Hydroxyethyl Starch Derivatives ; administration & dosage ; pharmacology ; Intestine, Small ; metabolism ; Isotonic Solutions ; administration & dosage ; pharmacology ; Male ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; therapy ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms. METHODS: The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects. RESULTS: GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 μg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 μg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination. CONCLUSION GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.
Apoptosis ; Cell Line, Tumor ; drug effects ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Grape Seed Extract ; pharmacology ; Humans ; MicroRNAs ; genetics ; metabolism ; Pancreatic Neoplasms ; pathology ; Proanthocyanidins ; pharmacology ; Up-Regulation

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

Objective To investigate the effect and mechanism of mitomycin C in reducing hypertrophic scar in rat traumatic osteomyelitis model.Methods A total of 120 Wistar rats were divided into control group (Group A,n =40),traumatic osteomyelitis group (Group B,n =40),traumatic osteomyelitis treated with Mitomycin C group (Group C,n =40),according to the random number table.The model of traumatic osteomyelitis was produced by Staphylococcus aureus.Muscle tissues around the focus were harvested at 15 d and 30 d postinjury.HE staining was used to observe the changes of muscle tissue structure.Immunohistochemistry was used to detect expression of transforming growth factor (TGF)-β1.Masson staining was used for collagen deposition evaluation.Western blot was used for detection of levels of TGF-β1 and collagen Ⅰ.Results HE staining revealed consistent alignment of fibers within the muscle in Group A.Fibrosis with the muscle was observed in both Group B and C,but the degree of muscle fiber disorder was decreased in Group C compared to Group B.Either 15 d or β0 d after injury,expressions intensity of TGF-β1,collagen fraction volume,and activation levels of TGF-β1 as well as collagen Ⅰ were higher in Group B and C than Group A,and all parameters were decreased in Group C compared to Group B (all P ＜ 0.05).Conclusion Mitomycin C can reduce hypertrophic scar formation in traumatic osteomyelitis model,and the potential mechanism relates to downregulated TGF-β1 and collagen Ⅰ.