Objective To investigate the influence of Tanyu-Tongzhi (TYTZ)recipe on Rho/Rho kinase signal transduction pathway of myocardial ischemia-reperfusion injury in high fat-fed rats.Methods 60 SD rats were divided into 5 groups randomly,a sham-operated group,a model group,a western medicine control group,a high-dose group and a low-dose group of TYTZ recipe.The model of ischemia reperfusion of the myocardium was reproduced by ligation of left descending artery for 30 min followed by releasing the ligation for 2 hours in rats.The downstream substrates of ROCK myosin light chain (MLC) phosphorylation expression of myocardial tissues in rats were detected by Western blotting method.The levels of RhoA,ROCK Ⅱ mRNA were determined with RT-PCR.Results Compared with the model group,the expression of p-MLC and RhoA,ROCK Ⅱ mRNA were lower in low-dose group of TYTZ,there were significant differences between the two groups(P=0.004、0.003、0.018、0.004,P＜0.01).Conclusion The TYTZ Recipe can protect myocardium from MI/RI.The mechanism of action was related to its inhibiting the protein expression of RhoA,ROCK Ⅱ and p-MLC,restraining the activation of Rho/Rho kinase signal transduction pathway.

Three-electrode testing method was used to investigate the effect of temperature on electrode impedance, and the pH shifts in saline solution resulting from the electrical stimulation were also determined. Experiments in PBS (phosphate buffered solution) solution showed that the electrode impedance was almost invariable at the human body temperature range (35 degrees C-40 degrees C). And the experiments in unbuffered saline solution showed that pH shifts decreased from 0.03 to 0.005 when the frequency of biphasic charged-balanced pulses increased from 1 Hz to 100 Hz. Even stimulated by monophasic pulses (frequency is 15 Hz, amplitude is 50 microA), the stimulus-induced pH shift of electrode only varies 0.15 (anodic pulse current increased 0.15 and cathodic pulse current decreased 0.15).
Electrochemistry ; Eye, Artificial ; Materials Testing ; Microelectrodes ; Prostheses and Implants

OBJECTIVETo investigate the influence of Tanyu Tongzhi (TYTZ) recipe on chemorheology, blood lipid and inflammatory factors of hyperlipidemia and myocardial ischemia-reperfusion injury in rats.

METHODSixty SD male rats were divided into 5 groups randomly, sham-operated group, model group, high dose group of reproduced by ligation of left descending artery for 30 min followed by releasing the TYTZ and low group of TYTZ. The model of MI/RI injury of the myocardium was ligation for 2 hours in rats. Serum contents of CHO, TG, HDL-L, LDL-L and whole blood viscosity, plasma viscosity and ICAM-1, TNF-alpha, IL-10 were measured after myocardial reperfusion injury.

RESULTCompared with sham-operated group, the levels of CHO, TG, LDL-L, whole blood viscosity (1.0,3.0) plasma viscosity and the contents of ICAM-1 were significantly higher, however, HDL-L, IL-10 levels were lower in model group (P < 0.01 and P < 0.05). CHO, TG, whole blood viscosity (1.0, 3.0, 30) and expression of ICAM-1, TNF-alpha were obviously lower in low group than the model group (P < 0.01 and P < 0.05).

CONCLUSIONThe TYTZ recipe can relieve reperfusion injury through regulating blood lipid, improving hemorheological characteristic and inhibiting inflammatory reaction.

Animals ; Blood Proteins ; analysis ; metabolism ; Blood Viscosity ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart ; drug effects ; Hemorheology ; drug effects ; Hyperlipidemias ; drug therapy ; Inflammation ; blood ; prevention & control ; Lipids ; blood ; Male ; Myocardial Reperfusion Injury ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To investigate on the prognosis factors of nosoco-mial pneumonia due to Pseudomonas aeruginosa in Southern Hospital. Methods By a retrospective study, the date of 136 cases of nosocomial pneumonia due to Pseudomonas aeruginosa in Southern Hospital were ana-lyzed. Results Multivariate Logistic regression analysis identified three independent factors: high clinical pulmonary infection score (CPIS) (OR = 5.01), Lower CPIS at day 5 (OR = 0. 001) and Pan-drug resistance Pseudomonas aeruginosa(OR =28. 80). Lower CPIS at day 5 is a protective factor. Empiric combination antibiotic therapy can increase the frequency of the lower CPIS at day 5. Conclusion High CPIS, lower CPIS at day 5 and Pan-drug resistance Pseudomonas aeruginosa were independent prognostic factors for nosocomial pneumonia due to Pseudomonas aeruginosa.

OBJECTIVETo evaluate the anti-angiogenic activity of peptide 21 obtained by modification of tumstatin, and its inhibitory effect on the growth and metastasis of human ovarian cancer transplanted in nude mice.

METHODSThe peptide 21 was purified by affinity chromatography. Human ovarian cancer SKOV3 cells were inoculated in nude mice and the transplanted tumor was treated with the peptide 21 to observe the tumor growth and metastasis. The microvessel density (MVD) and immunohistochemical staining index of PCNA, VEGF and MMP-2 and TIMP-2 were performed to assess the inhibitory effect of the peptide 21.

RESULTSIn the nude mice at 21 days after peptide 21 treatment, the inhibition rate of tumor growth was 53.17%, the tumor microvessel density was significantly reduced (P <0.05), the expression of PCNA, VEGF and MMP-2 were significantly lower (P <0.01), and TIMP-2 expression was significantly higher (P <0.01) in comparison with that of control group.

CONCLUSIONThe peptide 21 generated in this study has a significant anti-angiogenetic activity, showing significant inhibitory effect on the growth of human ovarian cancer transplanted in nude mice. The mechanism of its inhibitory action on ovarian cancer growth may be mediated by reduction of neovascularization and reduction of expression of angiogenetic factors.

Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Antigens, CD34 ; metabolism ; Antineoplastic Agents ; chemistry ; pharmacology ; Autoantigens ; chemistry ; pharmacology ; Cell Line, Tumor ; Collagen Type IV ; chemistry ; pharmacology ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; pathology ; prevention & control ; Ovarian Neoplasms ; metabolism ; pathology ; Peptides ; chemistry ; pharmacology ; Proliferating Cell Nuclear Antigen ; metabolism ; Recombinant Proteins ; chemistry ; pharmacology ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; enzymology ; pathology ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Esophageal Neoplasms ; drug therapy ; enzymology ; pathology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; metabolism ; Humans ; Mitogen-Activated Protein Kinase Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-raf ; antagonists & inhibitors ; metabolism ; Signal Transduction ; drug effects ; ras Proteins ; antagonists & inhibitors ; metabolism

Objective To explore the mechanism of'homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a protein-protein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(GO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9 962 targets of coronary heart disease,5 735 targets of arrhythmia and 7 722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao Decoction'homotherapy for heteropathy'were the response to hormones,the positive regulation of circulatory system process,phosphorus metabolism process,the response to exogenous stimulation,and the response to organic matter,the main cellular components(CC)include lipid rafts,receptor complexes,cytoplasmic perinuclear regions,dendrites,membrane sides,etc.,the main molecular functions(MF)include protein kinase activity,kinase binding,protein homopolymerization activity,nuclear receptor activity,heme binding,etc..KEGG pathway enrichment analysis showed that the main signaling pathways involved in Zhigancao Decoction'homotherapy for heteropathy'were lipid and atherosclerosis,calcium signaling pathway,cAMP signaling pathway,insulin resistance,cGMP-PKG signaling pathway,JAK-STAT signaling pathway,NF-κB signaling pathway,etc..The results of molecular docking suggested that there was a good binding activity between the main active component targets of Zhigancao Decoction and the core targets of'homotherapy for heteropathy'.Conclusion Zhigancao Decoction mainly regulates JAK-STAT,NF-κB,cAMP and other signaling pathways,acts on IL-6,STAT3,TNF,MMP-9 and other gene targets,and exerts the effect of'homotherapy for heteropathy'on coronary heart disease arrhythmia and pulmonary fibrosis.

OBJECTIVETo screen the polypeptides specifically binding to human large intestinal cancer LoVo cells from a phage-displayed peptide library for potential use as targeting vectors for large intestinal cancer therapy.

METHODSWith the LoVo cells as the target cells and human normal large intestinal mucosal epithelial cells as the absorber cells for subtraction biopanning from a c7c phage-display peptide library, the positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence detection. The amino acid sequences of the identified peptides were deduced by DNA sequencing.

RESULTSAfter 3 rounds of screening, 5 positive phage clones showing specific binding to LoVo cells and containing conserved motif RPMP were obtained from the 20 randomly selected clones.

CONCLUSIONSpecific peptide against large intestinal cancer cells can be obtained from a phage-display peptide library for use as potential vectors for targeting therapy of large intestinal cancer.

Amino Acid Sequence ; Base Sequence ; Binding, Competitive ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Humans ; Molecular Sequence Data ; Peptide Library ; Peptides ; genetics ; isolation & purification ; metabolism ; Protein Binding

Objective To evaluate the efficacy and safety of oxiracetam in the treatment of neurological deficits resulting from brain injury through the comparison of oxiracetam for injection and piracetam for injection in clinical trials. Methods A multiple-center, randomized, double-blind,parallel study was performed on 239 patients; these patients were divided into experimental group (oxiracetam for injection, n=120) and control group (piracetam, n=119). National institutes of health stroke scale (NIHSS), Glasgow coma scale (GCS), myodynamia grading, mini-metal state examination (MMSE) were employed to evaluate the therapeutic effects; electrocardiogram and laboratory examination were performed, and the side effects were also observed. Results The scores of NIHSS,GCS and myodynamia grading after treatment in the 2 groups were all significantly higher than those before treatment (P＜0.05); however, no significant differences on these scores were noted between the experimental group and control group (P＞0.05). No serious adverse events were noted in both groups.Conclusion Oxiracetam, the same as piracetam, is safe and effective in the treatment of neurological deficits secondary to brain injury.

Isotemporal substitution model is a powerful tool to explore the real association between physical behavior and health outcomes, which has the potential of the application in large-scale cohort study. This paper systematically introduces the principle of isotemporal substitution model and its implementation method in specific analysis to provide analytical ideas for the epidemiological research related to physical behavior in China. The baseline data of Regional Ethic Cohort Study in Northwest China conducted in Shaanxi province were used to analyze the relationship between physical behavior and cardiovascular disease with single-factor model, partition model and isotemporal substitution model. The advantages and disadvantages of different models were compared, and the advantages of isotemporal substitution model in quantifying physical activity health risk were introduced. Isotemporal substitution model could qualify physical behavior and health outcomes, which has wide application value in epidemiological research.
Humans ; Cohort Studies ; Epidemiologic Studies ; Cardiovascular Diseases ; China/epidemiology*