There are 250 species of Zanthoxylum (Rutaceae) in the world. This genus distributed in tropical and subtropical regions. Alkaloids are the major and representative ingredients in these plants including quinolines, isoquinolines, and amide alkaloids, with such biological activities as anti-tumor, anti-inflammatory, analgesic, anti-virus, anti-platelet aggregation, anti-bacteria and anti- oxidant. These species have been used for a long time to treat toothache, urinary and venereal diseases, lumbago and rheumatism. This review summarizes the chemical constituents and pharmacological activities from the Z. sppplants, in an effort to the systematic research and application of the alkaloids of this genus.
Alkaloids ; chemistry ; pharmacology ; Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Zanthoxylum ; chemistry

Objective To examine the neural basis of item memory and source memory with fMRI approach.Methods Eight male and eight female healthy fight-handed native Chinese speakers were involved in this study.The item memory and source memory task were conducted with 504 highly frequent Chinese double-character words in the Block-designed experiment.Participants underwent such a double- round procedure as fMRI scanning following study.The fMRI data collected from a GE 1.5T MRI system were analyzed to generate corresponding activation maps for females and males respectively(P20)using statistical parametric mapping software(SPM).Results For females,item memory task activated the bilateral dorsolateral prefrontal cortex(BA6,the number of activated voxel clusters was 62 or 11 in the left and the right,respectively),source memory more activated the left dorsolateral prefrontal cortex(BA6/46,the number was 59).For males,item memory activated the right dorsolateral prefrontal cortex(BA6/46,the number was 64),source memory activated the bilateral dorsolateral prefrontal cortex(BA6,9 and 40 in the left and the right).Conclusion On the neural basis of item or source memory,there exists dissociation,which is that right dorsolateral prefrontal areas are more activated by item memory while left dorsolateral prefrontal areas by source memory.For the difference of gender,it is suggested that left dorsolateral prefrontal areas(BA6/46)are more activated in females while right dorsolateral prefrontal cortex(BA6/46)more in males.

ObjectiveTo investigate the effect of hyperbaric oxygen (HBO) on proliferation and differentiation of endogenous neural stem cells after acute spinal cord half cut-off in rats. MethodsThe differences of proliferation and differentiation of endogenous neural stem cells between injured group and intervention group were compared. ResultsThere were remarkable differences between injured group and intervention group. ConclusionHBO can promote the proliferation and differentiation of the neural stem cells in rats after spine cord injury.

OBJECTIVETo investigate the selective killing of colorectal tumor cells by lentivirus-mediated double suicide gene under the regulation of KDR promoter.

METHODS293T packaging cells were transfected with the plasmid FGW-KDRP-CD/TK to obtain the infectious viruses. KDR-expressing LoVo cells and LS174T cells that did not produce KDR were transfected with the recombinant virus, and the transfection efficiency was evaluated by the fluorecence microscope. RT-PCR was employed to examine the expression of CDglyTK. After treatment of the cells with 5-FC and GCV, the killing effects on the two cell lines were evaluated.

RESULTSThe recombinant construct showed similar infection rate of the two cell lines. RT-PCR demonstrated that CDglyTK gene was expressed only in LoVo cells infected with FGW-KDRP-CD/TK but not in LS147T cells, and the sensitivity of the two cell lines to the prodrugs was significantly different (P<0.001). The killing effect of the double suicide gene was much stronger than that of single suicide gene administered (P<0.001).

CONCLUSIONThe double suicide gene driven by KDR promoter has specific killing effect on the KDR-expressing colorectal tumor cells.

Antimetabolites ; pharmacology ; Apoptosis ; drug effects ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Cytosine Deaminase ; genetics ; metabolism ; Flow Cytometry ; Flucytosine ; pharmacology ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; Promoter Regions, Genetic ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; Thymidine Kinase ; genetics ; metabolism ; Transfection ; Vascular Endothelial Growth Factor Receptor-2 ; genetics

OBJECTIVETo study the selective cytotoxic effect of lentivirus-mediated double suicide gene (CD/TK) against human gastric carcinoma cells SGC-7901 in vitro.

METHODSSGC-7901 cells were infected with FGW-KDRP-CD/TK vector and the infection efficiency was observed under a fluorescence microscope. The morphological changes of the infected cells were observed by Giemsa staining. Flow cytometry (FCM) was employed for cell cycle analysis, and the expression of CD/TK was detected by RT-PCR. The infected cells were then treated with the prodrugs ganciclovir (GCV) and/or 5-fluorocytosine (5-FC) at different concentrations, and the cytotoxic effects were evaluated using MTT method.

RESULTSThe infection efficiency of the lentiviral vector in SGC-7901 cells increased with the titer of the virus, which produced no significant effect on the cancer cell morphology in vitro or on the percentages of G0-G1, G2-M and S phase cells (P>0.05). RT-PCR demonstrated the expression of CD/TK gene in SGC-7901 cells infected by FGW-KDRP-CD/TK. The infected cells were highly sensitive to the prodrugs with a dose-dependent cytotoxic effect within a specific concentration range of the drugs, whereas the non-infected cells were not sensitive to the prodrugs. Combined use of the two prodrugs produced an obviously stronger inhibitory effect than either of the them (P<0.05). When combined, GCV and 5-FC at the concentration of 0.1+40, 1+80, 10+160, and 100+320 mg/L demonstrated a synergetic effect with a CDI<1.

CONCLUSIONLentivirus-mediated CD/TK fusion gene system can selectively kill gastric cancer cells, and the two prodrugs show a synergistic cytotoxic effect.

Adenocarcinoma ; genetics ; pathology ; Cell Line, Tumor ; Cytosine Deaminase ; biosynthesis ; genetics ; Cytotoxins ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology ; Stomach Neoplasms ; genetics ; pathology ; Thymidine Kinase ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo study the effect of adenovirus (Ad)-mediated fusion gene system driven by KDR promoter on the proliferation of human stomach adneocarcinoma SCG7901.

METHODSThe KDR-expressing SCG7901 cells and HepG2 cells that did not express KDR were both transfected with AdEasy-KDR-CDglyTK followed by treatment with the prodrugs 5-FC and/or GCV at different concentrations. The killing effects of the transfection on the cells were evaluated.

RESULTSThe expression of green fluorescent protein (GFP) was observed in 95% of the infected SCG7901 and HepG2 cells with the multiple of infection (MOI) of the Ads of 100. Transfection of SCG7901 and HepG2 cells did not produce significant changes in the cell growth, and the infected cells exhibited different sensitivities to the two prodrug: SCG7901 cells infected with rAd were highly sensitive to the prodrugs, but the infected HepG2 cells were not (P<0.01). The killing effect of CDglyTK fusion gene on the target cells was much stronger than that of either the single suicide gene (P<0.01).

CONCLUSIONCDglyTK fusion gene system driven by KDR promoter selectively kills the KDR-CDglyTK SCG7901 cells and inhibits their proliferation.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Adenoviridae ; genetics ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Flucytosine ; pharmacology ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Vectors ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Neovascularization, Pathologic ; genetics ; metabolism ; pathology ; Prodrugs ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transfection ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis ; genetics

It is now well established that inflammation plays an important role in the development of numerous chronic metabolic diseases including insulin resistance (IR) and type 2 diabetes (T2DM). Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Our pre- vious study has shown that rutaecarpine (Rut) can benefit blood lipid profile, mitigate inflammation, and improve kidney, liver, pan- creas pathology status of T2DM rats. However, the effects of Rut on inflammatory cytokines in the development of IR-skeletal muscle cells have not been studied. Thus, our objective was to investigate effects of Rut on inflammatory cytokines interleukiri (IL)-1, IL-6 and tumor necrosis factor (TNF)-α in insulin resistant primary skeletal muscle cells (IR-PSMC). Primary cultures of skeletal muscle cells were prepared from 5 neonate SD rats, and the primary rat skeletal muscle cells were identified by cell morphology, effect of ru- taecarpine on cell proliferation by MTT assay. IR-PSMC cells were induced by palmitic acid (PA), the glucose concentration was measured by glucose oxidase and peroxidase (GOD-POD) method. The effects of Rut on inflammatory cytokines IL-1, IL-6 and TNF-α in IR-PSMC cells were tested by enzyme-linked immunosorbent assay (ELISA) kit. The results show that the primary skeletal muscle cells from neonatal rat cultured for 2-4 days, parallel alignment regularly, and cultured for 7 days, cells fused and myotube formed. It was shown that Rut in concentration 0-180. 0 μmol x L(-1) possessed no cytotoxic effect towards cultured primary skeletal muscle cells. However, after 24 h exposure to 0.6 mmol x L(-1) PA, primary skeletal muscle cells were able to induce a state of insulin resistance. The results obtained indicated significant decrease (P < 0.05 to P < 0.001) IL-1, IL-6 and TNF-α production by cultured IR-PSMC cells when incubating 24 hours with Rut, beginning from 20 to 180.0 μmol x L(-1). IL-1, IL-6 and TNF-α in the Rut treated groups were dose-dependently decreased compared with that in the IR-PSMC control group. Our results demonstrated that the Rut promoted glucose consumption and improved insulin resistance possibly through suppression of inflammatory cytokines in the IR-PSMC cells.
Animals ; Cell Proliferation ; drug effects ; Cytokines ; metabolism ; Female ; Glucose ; metabolism ; Indole Alkaloids ; pharmacology ; Inflammation ; metabolism ; Insulin Resistance ; Male ; Muscle, Skeletal ; cytology ; drug effects ; metabolism ; Quinazolines ; pharmacology ; Rats

BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI). METHODS: A ALI rat model was produced by intravenous infusion of lipopolysaccharide (6 mg/kg). Twenty-five rats were randomly divided into five groups: control group (n=5), ALI group (n=5), low tidal volume group (LV group, VT 6 mL/kg, n=5), sustained inflation (SI) with low tidal volume group (SI+LV group, VT 6 mL/kg, n=5), and SI with moderate tidal volume group (SI+MV group, VT 12 mL/kg, n=5). RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end-expiratory pressure (PEEP) was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure (MAP) was monitored during the experiment. Endothelin-1 (ET-1), endothelial nitricoxide synthase (eNOS), Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS: LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI+LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS: RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.

Objective To explore the relationship between receptor of advanced glycaton end products(RAGE)gene Gly82Ser polymorphism and patients with transient ischemia attack(TIA).Methods The Gly82Ser gene at the position of RAGE gene exon 3 was identified by a polymerase chain reaction- restriction fragment length polymorphism(PCR-RFLP)method in 70 cases of TIA & Diabetes(DM), 60 of simply TIA and 66 healthy control subjects.Results The genotypes of RAGE gene Gly82Ser identified were GG, GS and SS.The frequencies of RAGE gene Gly82Ser GS heterozygous genotype of TIA & DM and control were respectively 62.9% and 43.9%, significantly higher in TIA & DM patients than in control subjects(OR 2.036, 95% CI 1.021--4.062, P=0.042), however no significant difference was found between simply TIA and control(53.3% vs 43.9%, OR 1.299,95% CI O.644--2.618, P=0.465). Significant difference of the frequency of S allele was found neither between TIA & control and control(being 34.3% and 26.5%, respectively, OR 1.446,95% CI 0.859--2.434, P=0.164), nor between simple TIA and control(28.3% vs 26.5%, OR 1.096,95%CI 0.630--1.907, P=0.746).Conclusions RAGE gene Gly82Ser GS heterozygous genotype may be associated with TIA & DM patients.RAGE gene Gly82Ser polymorphism is a risky factor for TIA & DM patients, but not for TIA patients.

OBJECTIVETo detect the possible relationship between PARKIN gene and the Chinese pedigree with autosomal recessive early-onset Parkinson's disease(AREP).

METHODSClinical examination was carried out in 6 patients from 3 Chinese pedigrees with AREP and their 23 family members. PCR amplification of all exons of PARKIN gene was performed. The PCR products were analyzed by denaturing high-performance liquid chromatography(DHPLC) to screen for point mutation and polymorphism. And in the samples with abnormal DHPLC result, further sequencing was conducted to confirm the type of mutation and polymorphism.

RESULTSAll exons of PARKIN gene from the research subjects were successfully amplified. A heterozygous point mutation (Gly284Arg) in exon 7 was found in one pedigree. A polymorphism (Ser167Asn) in exon 4 was found in another pedigree. All the patients had the past history of exposure to environmental poison.

CONCLUSIONWhen acting together with risky environmental factors, the heterozygous mutation Gly284Arg in PARKIN gene may cause AREP. The polymorphism Ser167Asn in PARKIN gene increases the risk of developing Parkinson's disease and may cause AREP when acting together with hydrargyrism.

Age of Onset ; Aged ; China ; epidemiology ; Chromatography, High Pressure Liquid ; Exons ; genetics ; Female ; Genes, Recessive ; Humans ; Male ; Middle Aged ; Parkinson Disease ; epidemiology ; genetics ; Pedigree ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Ubiquitin-Protein Ligases ; genetics