Objective: To observe the efficacy of acupoint sticking with Jianpi Tongjing Zhitong ointment in the treatment of functional dyspepsia due to liver-qi stagnation and spleen deficiency and its effect on serum 5-hydroxytryptamine (5-HT) and ghrelin contents. Methods: One hundred patients with functional dyspepsia due to liver-qi stagnation and spleen deficiency were divided into a treatment group and a control group by the random number table method, with 50 cases in each group. The treatment group received acupoint sticking with Jianpi Tongjing Zhitong ointment and the control group was treated with mosapride citrate orally. Patients were treated for 4 weeks as a course. The therapeutic efficacy was compared after one-course treatment and the differences in gastric emptying rate, and serum 5-HT and ghrelin contents between groups were compared before and after treatment. Results: The total effective rate was 79.6％ in the control group and 89.4％ in the treatment group, showing significantly different between groups (P<0.05). After treatment, the gastric emptying rate and serum ghrelin content of the two groups increased significantly, and the serum 5-HT content decreased significantly, the intra-group differences were significant (all P<0.01). After treatment, the gastric emptying rate and serum ghrelin content were significantly higher in the treatment group than those in the control group, while the serum 5-HT was significant lower in the treatment group, the inter-group differences were significant (all P<0.05). A negative correlation (r=-0.59) was observed between serum 5-HT content and gastric emptying rate, and a positive correlation (r=0.64) was observed between serum ghrelin content and gastric emptying rate, showing statistical significance (all P<0.01). Conclusion: Acupoint sticking with Jianpi Tongjing Zhitong ointment has a remarkable clinical efficacy in treating patients with functional dyspepsia due to liver-qi stagnation and spleen deficiency and is able to influence the secretion of serum 5-HT and ghrelin. Improving the gastrointestinal motility through the regulation of related brain-gut peptides is suggested as an underlying mechanism for this therapy.

Actin cytoskeleton in podocyte is a complicated network structure,and the stability of this structure depend on many proteins which located in slit diaphragm,the apical membrane domain and the basal membrane domain with the stimulus of mechanical stress,the actin cytoskeleton can be adaptive regulated to maintain the normal function of glomerulus,and several signal pathways involve in the process,such as RhoA/Rho kinase signal pathway and TRPC6.

Child ; Crush Syndrome ; complications ; Female ; Humans ; Male ; Pulmonary Edema ; complications

Abstract: Fifteen novel ligustrazine-tetrahydroisoquinoline derivatives were designed and synthesized according to the association principle of pharmaceutical chemistry. The structures were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by ADP and AA have been measured by Bron method. Preliminary pharmacological results showed that compounds 7g, 7h and 7n had potent inhibitory activity against platelet aggregation induced by AA, and the compound 7o showed significant inhibitory activity against platelet aggregation induced by ADP.
Drug Design ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Pyrazines ; chemical synthesis ; chemistry ; Tetrahydroisoquinolines ; chemical synthesis ; chemistry

For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1 promoter activity was detected by Dual-Luciferase Reporter Assay System, it came that the relative luciferase activity of COL1A1 promoter was 15.98 times higher than that of control group induced by TGF-β1, showing the recombined plasmid could be used in cell model. The recombined plasmid was transfected into human hepatic stellate cells LX2, detected the effect of potential drugs, and obtained a stable expression system through stable transfection and monoclonal cell culture. A sample which could reduce COL1A1 promoter activity signally by our cell model, decreased collagen I mRNA and protein expression detected by real-time RT-PCR and Western blotting. It indicates this novel cell model can be used in high-throughput drug screening of potential anti-liver fibrosis drugs.
Collagen Type I ; genetics ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; Hepatic Stellate Cells ; High-Throughput Screening Assays ; Humans ; Liver Cirrhosis ; drug therapy ; Luciferases ; Plasmids ; Promoter Regions, Genetic ; RNA, Messenger ; Transfection ; Transforming Growth Factor beta1 ; pharmacology

Humans ; Metals ; Microwaves ; adverse effects ; Occupational Exposure ; adverse effects ; analysis ; Workplace

Antibodies ; analysis ; Biopsy ; Child ; Child, Preschool ; Disease Progression ; Drug Resistance ; Female ; Fluorescent Antibody Technique ; Humans ; Immunoglobulin A ; analysis ; Kidney Glomerulus ; immunology ; pathology ; Male ; Nephrosis ; drug therapy ; pathology ; Prognosis ; Steroids ; pharmacology ; therapeutic use

Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.
CDC2 Protein Kinase ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; G1 Phase ; drug effects ; Hep G2 Cells ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; Thiazoles ; pharmacology

This study aimed to investigate the synergistic effect of lidamycin (LDM) and rituximab on human B cell lymphoma Ramos cells. Cell proliferation was measured using MTS assay, cell apoptosis was analyzed by Annexin V-FITC/PI assay, the expression of apoptosis related proteins was analyzed by Western blotting, and the in vivo lymphoma inhibition was verified using BALB/c mice inoculated via tail vein using Ramos cells which stably expressed pEGFP-N1 plasmid. The results showed that, after the pretreatment with rituximab for 48 h, rituximab and LDM showed significantly synergistic effects on cell proliferation. Cells in combined treatment group had a higher apoptosis rate than that in LDM treatment group. Compared with the LDM treatment group, the expression of apoptosis-related proteins such as Cleaved caspase-3, Cleaved caspase-7, Cleaved caspase-9 and Cleaved PARP in combined treatment groups increased, and expression of cIAP-2 and Bcl-2 decreased. The result of in vivo experiment showed that, in the combined treatment group, the survival time of BALB/c mice was significantly longer than the mice in control group and LDM treatment group, and the degree of tumor accumulation and metastasis to lymph nodes and spleen was lower.
Aminoglycosides ; pharmacology ; Animals ; Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 7 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Enediynes ; pharmacology ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Lymphoma, B-Cell ; metabolism ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; Neoplasm Transplantation ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Random Allocation ; Rituximab ; pharmacology

A geldanamycin (GDM) producing strain, Streptomyces hygroscopicus 17997, was isolated from Yunnan China soil by our institute researchers. GDM is an ansamycin antibiotic, which has the ability to bind with Hsp90 (Heat Shock Protein 90) and alter its function. Hsp90 is a chaperone protein involved in the regulation of the cell cycle, cell growth, cell survival, apoptosis, and oncogenesis. So it plays a key role in regulating the physiology of cells exposed to environmental stress and in maintaining the malignant phenotype of tumor cells. As an inhibitor of Hsp90, GDM possesses potent antitumor and antivirus bioactivity, but the hypato-toxicity and poor solubility in water limits its clinical use. Two GDM derivatives, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) and 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG), both showing lesser hepato-toxicity, are now in Phase II and Phase I clinic trials. In order to accomplish the structure modification of GDM by genetic means, an attempt to obtain the biosynthetic gene cluster of GDM from S. hygroscopicus 17997 was made. In this study, a pair of primers was designed according to a conserved sequence of one of possible post-PKS (polyketides synthase) modification genes, the carbamoyltransferase (CT) gene (gdmN) in GDM biosynthesis. The 732 bp PCR product was obtained from the S. hygroscopicus 17997 genomic DNA. Through the colony-PCR Binary Search Method, using the CT gene primers, six positive cosmid clones, CT1-6, were identified from the S. hygroscopicus 17997 cosmid genomic library. The CT gene containing fragments were verified and localized by Southern blot. The CT-4 positive cosmid was then sub-cloned and sequenced. Approximately 28.356kb of foreign gene sequence from CT-4 cosmid and by further PCR extension reaction was obtained. Based on BLAST analysis, this sequence contains 13 possible ORFs and their deduced functions are believed to be involved in GDM production. The ORF1 encoding products show homology (87%) with incomplete sixth module and complete seventh module of PKS, gdmA3, in S. hygroscopicus NRRL 3602. The ORF2-13 gene products are similar to gdmF(9 5%), gdmM(8 8%), gdmN (92%), gdmH (92%), I (93%), J (90%), K (93%), G (96%), gdmO (91%), gdmP (93%) and two transcription regulation genes gdmRI (83%) and gdmRII (90%). The obtained possible GDM biosynthetic gene cluster in S. hygroscopicus 17997 will facilitate the further functional analysis of the genes and to modify the structure of GDM through combinatorial biosynthesis.
Anti-Bacterial Agents ; metabolism ; Benzoquinones ; metabolism ; Carboxyl and Carbamoyl Transferases ; genetics ; Chromosome Mapping ; Cloning, Molecular ; DNA Primers ; genetics ; Lactams, Macrocyclic ; metabolism ; Multigene Family ; Streptomyces ; genetics ; metabolism