High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
Animals ; Biomarkers ; blood ; Blood Pressure ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Least-Squares Analysis ; Mass Spectrometry ; Metabolome ; Metabolomics ; Rats ; Rats, Inbred SHR ; Valsartan ; pharmacology

Config and modify open source software such as Nagios、 MRTG and Awstats, make it more suitable and stable for our network environment. Construct server monitor、 service monitor、 network monitor and website statistics system by using open source software. Besides, we construct network resource management system via ASP and database technology.Finish the network and service monitoring and management system based on B/S architecture. This system can keep close watch on the status of servers and services running on servers, and ensure all of the servers and services normal running, and provide the basic information service for policy-making body and other research institute.

Objective To investigate the protective effect of endotoxin pretreatment on hippocampal neurons in rat forebrain following ischemia reperfusion and its possible mechanism. Methods Rat forebrain ischemia reperfusion model was used. The effects of endotoxin pretreatment on the changes of superoxide dismutase (SOD), glutathione peroxidase (GSH PX) and malondialdehyde (MDA) activities and the neuron count in CA1 region were observed. Results Pretreament with endotoxin before cerebral ischemia enhanced the activities of SOD and GSH PX but decreased MDA level and the number of ischemic neurons in CA1 region. Conclusion Endotoxin pretreatment can protect the neurons in rat forebrain against ischemia reperfusion injury. The mechanism may be associated with the enhancement of endogenous antioxidant activity in central nervous system.

Puromycin-sensitive aminopeptidase (PSAP) belongs to the M1 family of aminopeptidases, characterized by the N-terminal substrate binding sequence GAMEN, the enzyme activity center HEXXH(X)₁₈E motif, and the C-terminal ERAP-1-like superfamily structural domain. Encoded by the gene NPEPPS located at 17q21.32, PSAP consists of 919 amino acids and is widely distributed throughout the human body, with the highest expression in the brain, followed by the heart and skeletal muscle. It is also found in the liver, renal tubular epithelium, small intestine, large intestine epithelium, and gastric epithelial cells. PSAP primarily relies on its aminopeptidase hydrolytic activity to remove toxic protein aggregates such as Tau, poly Q, and Cu, Zn-superoxide dismutase 1, making it an important factor in the development of diseases such as Alzheimer's disease, Huntington's chorea, and tumors. Existing PSAP inhibitors include bestatin, amastatin, leuhistin, actinonin, and purinomycin, some of which are already available or in clinical trials. This review provides an overview of the structural and biological functions of M1 family aminopeptidases, with a focus on PSAP, to facilitate further research and targeted drug development.

To develop a new small molecular probe for discovering an antitumor lead compound from the replacement of carboxylic group of two molecular antibacterial fluoroquinolones with a heterocyclic ring, a series of the C3/C3 bis-fluoroquinolones tethered with an 1, 3, 4-oxadiazole ring were synthesized as their respective HCl salts, and their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated via the respective IC50 values by methylthiazole trazolium (MTT) assay.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; drug effects ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Drug Design ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; drug effects ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

To develop gastric floating erodible plug pulse capsules with compound Danshen as the model drug, in order to realize the pulse release of traditional Chinese medicines. Through the study on impermeable capsules, optimized prescriptions, drug-containing rapid-release tablets and prescription screening, and erodible plug prescription and process, we successfully prepared compounded Danshen pulse capsule, so as to provide a new dosage form for controlling and treating heart disease to better cater to clinical demands.
Capsules ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Heart Diseases ; drug therapy ; Permeability ; Salvia miltiorrhiza ; chemistry

The aimed of this study was to prepare stabilized thiomers to overcome the poor stability character of traditional thiomers. Poly(acrylic acid)-cysteine (PAA-Cys) was synthesized by conjugating cysteine with poly(acrylic acid) and poly(acrylic acid)-cysteine-6-mercaptonicotinic acid (PAA-Cys-6MNA, stabilized thiomers) was synthesized by grafting a protecting group 6-mercaptonicotinic acid (6MNA) with PAA-Cys. The free thiol of PAA-Cys was determined by Ellmann's reagent method and the ratio of 6MNA coupled was determined by glutathione reduction method. The study of permeation enhancement and stabilized function was conducted by using Franz diffusion cell method, with fluorescein isothiocyanate dextran (FD4) used as model drug. The influence of polymers on tight junctions of Caco-2 cell monolayer was detected with laser scanning confocal fluorescence microscope. The results indicated that both PAA-Cys and PAA-Cys-6MNA could promote the permeation of FD4 across excised rat intestine, and the permeation function of PAA-Cys-6MNA was not influence by the pH of the storage environment and the oxidation of air after the protecting group 6MNA was grafted. The distribution of tight junction protein of Caco-2 cell monolayer F-actin was influenced after incubation with PAA-Cys and PAA-Cys-6MNA. In conclusion, stabilized thiomers (PAA-Cys-6MNA) maintained the permeation function compared with the traditional thiomers (PAA-Cys) and its stability was improved. The mechanism of the permeation enhancement function of the polymers might be related to their influence on tight junction relating proteins of cells.
Acrylic Resins ; chemistry ; Actins ; metabolism ; Animals ; Caco-2 Cells ; Cysteine ; chemistry ; Dextrans ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Glutathione ; Humans ; Intestinal Absorption ; Intestinal Mucosa ; drug effects ; Nicotinic Acids ; chemistry ; Rats ; Sulfhydryl Compounds ; chemistry

Objective To investigate the effects of caudal type homeobox 2 (Cdx2) silence on reservion of multi-drug resistance of gastric carcinoma cisplantin-resistant cell SGC7901/DDP.Methods Gastric carcinoma cisplantin-resistant cells SCG7901/DDP in the logarithmic phase were cultured in the plate,and were divided into the experimental group [gastric carcinoma cells of SGC7901/DDP were infected with a silent Cdx2-recombinanted lentiviral vector (pLL-Cdx2-shRNA)],the negative control group (gastric carcinoma cells of SGC7901/DDP were infected with empty lentiviral vector) and the blank control group (gastric carcinoma cells of SGC7901/DDP were not treated).The protein and mRNA expressions of Cdx2 and apoptosis related genes like c-myc,cyclin D1 and survivin were detected by the Western blot and reverse-transcription PCR,respectively.The sensitivity of the cells in the 3 groups to adriamycin,5-fluorouracil and cisplatium were assessed by MTT.The pump-out rate of adriamycin,cell cycle distribution and apoptosis of the 3 groups were analyzed using flow cytometry.All measurement data were expressed with mean ± standard deviation.Comparison among multi-groups was done by one-way analysis of variance,and comparison between 2 groups was done by SNK-q test.The enumeration data were analyzed using the chi-square test.Results The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.187 ± 0.060,0.086 ± 0.004,0.016 ± 0.005 and 0.276 ± 0.012 in the experimental group,0.535 ± 0.033,0.379 ± 0.006,0.141 ± 0.003 and 0.672 ± 0.009 in the negative control group,and 0.567 ± 0.014,0.354 ± 0.004,0.162 ± 0.008 and 0.517 ± 0.313 in the blank control group,respectively.The relative protein expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =247.385,3.353,597.882,98.628,P ＜0.05).The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin were 0.184 ± 0.010,0.212 ± 0.022,0.045 ± 0.009 and 0.401 ± 0.027 in the experimental group,0.894 ± 0.056,0.538 ± 0.021,0.163 ±0.009 and 0.824 ± 0.016 in the negative control group,and 0.837 ±0.049,0.545 ±0.032,0.157 ±0.010 and 0.782 ±0.056 in the blank control group,respectively.The relative mRNA expression levels of Cdx2,c-myc,cyclin D1 and survivin in the experimental group were significantly lower than those in the negative control group and the blank control group (F =243.776,161.793,138.523,118.426,P ＜ 0.05).The IC50 values detected by MTT of adriamycin,5-flurouracile and cisplatin to gastroc carcinoma cisplantin-resistant cell SCG7901/DDP were (0.12 ± 0.05) mg/L,(0.52 ± 0.13) mg/L and (0.82 ± 0.13) mg/L in the experimental group,(0.33 ± 0.08) mg/L,(4.10.± 1.25) mg/L and (2.81 ± 0.50) mg/L in the negative control group,(0.39 ±0.15)mg/L,(4.05 ± 1.44) mg/L and (3.28 ± 1.03) rng/L in the blank control group,respectively.The pump-out rates of adriamycin of the experimental group,negative control group,and the blank control group were0.21％,0.37％ and 0.35％.Compared with the negative control group and the blank control group,the IC50values of adriamycin,5-fluorouracil and cisplatin in the experimental group were significantly increased,and thepump-out rate of adriamycin was significantly decreased (F =8.101,13.854,15.159,x2 =7.106,P ＜ 0.05).The ratios of cells in the G0/G1 phase were 17.87％,34.71％ and 37.20％ in the experimental group,negative control group and the blank control group,respectively.Compared with the negative control group and blank control group,the ratio of cells in the G0/Gt was significantly decreased (x2=1.055,P ＜ 0.05).The ratio of cells in the G2/M phase in the experimental group was 11.93％,and the apoptosis rate was 31.13％,which were significantly higher than the negative group (0.26％,16.58％) and the blank control group (0.35％,13.18％) (x2=2.249,11.030,P ＜ 0.05).Conclusions Silent Cdx2 can effectively enhance the sensitivity of the SGC7901/DDP cells and the intracellular accumulation concentration of the drugs.Silent Cdx2 can also reverse the multidrug resistance of the SGC7901/DDP cells.

Objective To investigate the effect of ropiyacaine combined with intra-spinal epidural anesthesia by using the same volume but different injection speed on anaesthetic level.Methods 80 cases of patients of ASA～Ⅱdegree suitable to use intra-spinal epidural combined anesthesia for gynecologic operation were selected and ran- domly divided into three groups,0.75 % ropivacaine 2mg(15mg)administered,group A the speed of injection was 10 seconds,group B injection speed was 20 seconds,group C injection speed was 30 seconds,the anaesthetic level reached T_(10).The time of highest level in spinal anesthesia,30 minutes after spinal anesthesia MAP,and number of cases need to add epidural drug were all recorded.Results The best effect of anesthesia was found in group B,the block level of anesthesia was satisfactory,blood dynamic was stable,and there was no need to add epidural drug.Conclusion The speed of 0.75 % ropivacaine 2ml spinal epidural combined with anesthesia was suitable at the speed of 20 seconds.

Objective To explore therapeutic effects and mechanisms of radical scavenger edaravone on experimental cerebral hemorrhage.Methods Two hundred-forty male SD rats were divided randomly into four groups:control group,cerebral hemorrhage group,edaravone treatment group before operation (A) and edaravone treatment group after operation (B).Experimental cerebral hemorrhage model was made according to the method reported by Rosenberg.Water quantity contained in brain and nervous missing sign were observed,meanwhile the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue were measured.Results Compared with cerebral hemorrhage group,nervous missing sign and water quantity contained in brain obviously changed in edaravone treatment group (P