To study the preventive effect of sophocarpine (Soc) on dextran sulfate sodium (DSS)-induced colitis in mice, in order to analyze the influence of Soc on toll like receptor 4 (TLR4)/mitogen-activated protein kinases (MAPKs) and janus tyrosine kinase 2 signal transducer and activator of transcription 3 (JAK2/STAT3) signal pathways in mice intestinal tissues. The mice was given 2.5% DSS for 6 days to induce the acute colitis model. The Soc-treated group was intraperitoneally injected with sophocarpine 30 mg · kg(-1) · d(-1) since the day before the experiment to the end. The disease activity index (DAI) was assessed everyday, and the colonic morphology and histological damage were observed with HE staining. The mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected by real-time RT-PCR. The changes in key protein kinase p38 mitogen-activated protein kinase (p38MAPK), c-Jun NH2-terminal protein kinase1/2 (JNK1/2), extracellular signal-regulated kinase1/2 (ERK1/2), JAK2, STAT3 in TLR4/MAPKs and JAK2/STAT3 signaling pathways were detected by western blot. The result showed that the model group showed statistical significance in body weight, DAI, colon length and histopathological changes compared with the normal group (P <0.05); however, the Soc-treated group showed significant improvements in the above indexes compared with the model group (P <0.05). TNF-α, IL-1β and IL-6 in the model group was significantly higher than that in the normal group (P <0.05), but lowered in the Soc-treated group to varying degrees (P <0.05). In the normal group, the expressions of TLR4 and the phosphorylation of P38, JNK1/2, JAK2, STAT3 were at low levels; in the model group, the phosphorylation of P38, JNK1/2, JAK2, STAT3 increased; the Soc-treated group showed a decrease in TLR4 expression compared with the model group, with notable declines in the phosphorylation of TLR4, P38, JNK1/2, JAK2, STAT3. These findings indicate that Soc can inhibit TLR4/MAPKs, K2/STAT3 signaling pathway activation, reduce the expression of proinflammatory cytokines TNF-α, IL-1β and IL-6 and relieve inflammatory reactions, so as to effectively prevent experimental colitis.
Alkaloids ; pharmacology ; therapeutic use ; Animals ; Colitis ; drug therapy ; immunology ; pathology ; Cytokines ; genetics ; Janus Kinase 2 ; antagonists & inhibitors ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Phosphorylation ; STAT3 Transcription Factor ; antagonists & inhibitors ; physiology ; Toll-Like Receptor 4 ; antagonists & inhibitors ; physiology

OBJECTIVE: To investigate the relationship between serum asymmetric dimethylarginine (ADMA) and blood pressure as well as target organ damage in essential hypertension, and to evaluate the effects of enalapril and losartan on them. METHODS: Forty-two newly diagnoszed patients with essential hypertension were randomly divided into enalapril-treated group and losartan-treated group. Serum ADMA, L-arginine, and nitric oxide( NO) were measured before and after the treatment for 8 weeks. Twenty-three healthy volunteers were included as control subjects. RESULTS: The concentrations of ADMA and L-arginine in serum were significantly higher but the level of nitric oxide was relatively lower ( P < 0.01 ) in hypertensive patients than those in control subjects. Serum ADMA was higher in different levels of blood pressure and target organ damage. Treatment with enalapril or losartan for 8 weeks not only reduced blood pressure but also decreased serum ADMA (P <0.01 ). Furthermore, treatment with these drugs also increased the level of serum nitric oxide but didn't change the level of L-arginine. CONCLUSION The concentrations of serum ADMA and L-arginine were increased, but the level of nitric oxide was decreased in the early stage of essential hypertension. Both enalapril and losartan could ameliorate the endothelial function by reducing the concentration of ADMA.
Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Arginine ; analogs & derivatives ; blood ; Enalapril ; therapeutic use ; Female ; Humans ; Hypertension ; blood ; drug therapy ; Losartan ; therapeutic use ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; antagonists & inhibitors

OBJECTIVETo investigate if an adenovirus vector carrying antisense multidrug resistance gene 1 (MDR1) could reverse multidrug resistance (MDR) of HepG2/ adriamycin (ADM) cells in tumors transplanted in athymic mice.

METHODSAn adenovirus vector carrying AFP promoter and antisense MDR1 was constructed. HepG2 MDR cells (HepG2/ADM) were induced by graded resistance to ADM and were subcutaneously inoculated into athymic mice to construct the transplanted tumor. After adeno-asmdr1 was injected, the volume of the transplanted tumor and the apoptotic body in the xenograft tumor cells were observed and reverse transcriptase polymerase chain reaction was employed to investigate the expression of the mdr1-mRNA from the mouse transplanted tumor cells.

RESULTSFollowing injection with adeno-asmdr1, the tumor volumes in this mice group did not increase. However the tumor volume in the PBS plus ADM group did increase significantly (P less than 0.05). In the tumor xenograft cells, mdr1 mRNA in the xenografts was assessed by RT-PCR and found to be reduced at week 1, and at week 4 in the ADM+asmdr1 group, but it was stable in the ADM group. It was only 20% in the ADM+asmdr1 group compared to the ADM group at the 4th week. Evidence of apoptosis was observed in the tumor xenograft cells treated with adeno-asmdr1, but there was rarely any apoptosis in the group treated with ADM and PBS.

CONCLUSIONAdenovirus carrying antisense mdr1 RNA can partially reverse the MDR of HepG2/ADM cells and inhibit tumor growth by down-regulating mdr1 mRNA resulting in tumor cell apoptosis.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Adenoviridae ; genetics ; Animals ; Carcinoma, Hepatocellular ; drug therapy ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Genetic Vectors ; Hep G2 Cells ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; RNA, Antisense ; genetics

Alveolar epithelial type II (AT II) cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells (fibroblasts). Progenitor cells are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells (H441) transfected with TK gene had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549). In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell (AT II) niche in vitro and in vivo.

Adult ; Aged ; Female ; Hemangiosarcoma ; diagnostic imaging ; Humans ; Liver Neoplasms ; diagnostic imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo observe the changes in Th17 cell levels in bronchoalveolar lavage fluid in children of sepsis with acute lung injury and the relationship between the Th17 cell levels and prognosis.

METHODSFifty children of sepsis with acute lung injury were enrolled in the study. The percentages of Th17 cells in bronchoalveolar lavage fluid were measured by flow cytometry. The patients of sepsis with acute lung injury were classified into three groups based on the Pediatric Critical Illness Score (PCIS): extremely critical, critical and non-critical. According to the clinical prognosis, the patients were classified into survical and death groups. Th17 cell levels were compared between the two groups. The relationship between Th17 cell levels and the PCIS scores was analyzed.

RESULTSWith the increase in the severity of sepsis, Th17 cell levels in bronchoalveolar lavage fluid were gradually increased (P<0.05). The Th17 cell levels were negatively correlated to the PCIS scores (r=-0.853; P<0.01). The Th17 cell levels were significantly higher in the death group than in the survival group. Moreover, compared with the survival group, the PCIS scores were lower in the death group (P<0.05).

CONCLUSIONSThe increased Th17 cell levels in children of sepsis with acute lung injury are closely related to the severity and prognosis of patients, suggesting that Th17 cell levels can be used as a predictor of the severity and prognosis.

Acute Lung Injury ; immunology ; Bronchoalveolar Lavage Fluid ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Prognosis ; Sepsis ; immunology ; Severity of Illness Index ; Th17 Cells ; physiology

Alanine Transaminase ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B, Chronic ; virology ; Humans ; Male

To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant,and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development.

Objective To explore the effects of health belief model education on compliance about volume status in peritoneal dialysis patients. Methods 41 peritoneal dialysis patients who were followed-up regularly accepted health belief model education about volume control. Their volume status, compliance and cognition were analyzed. Results After the education, the patients' total fluids cleaning and KT/V decreased markedly, but their volume status had no difference (P＞0.05); Their compliances with dialysis prescription and taking medicine remained good (＞80%), while the compliances in salt and water diet had statistical meaning (P＜ 0.05). And their cognitions in every aspect had obvious improvement (P＜0.05). Conclusions Health belief model education could improve peritoneal dialysis patients' compliance about volume status, thus improving their volume status.

OBJECTIVETo investigate the anti-tumor effect of intraportal administration of Adv-p53 in the treatment of the liver metastasis in mice.

METHODS2 x 10(5) of MCA-205 cells were injected into the mouse portal vein to establish a murine liver metastasis model. The spleen was transpositioned subcutaneously to enable the administration of Adv-p53 continually into the portal system. Different doses of Adv-p53 were injected intraportally, while HBSS and Adv-CMV were injected intraportaly in the control group. Tumors in the liver were examined on day 21 after Adv-p53 administration.

RESULTSThe liver weight in the Adv-p53 treated mice on day 0 group (1.20 +/- 0.34 g) was significantly less than that in the Adv-CMV group (2.59 +/- 0.48 g, P < 0.05). The number of metastatic nodules in the Adv-p53 treated mice on day 0 group (9.0 +/- 9.9) was significantly less than that in the Adv-CMV group (57.1 +/- 11.3, P < 0.05), indicating that intraportal administration of Adv-p53 inhibited the formation of liver metastasis. This anti-tumor effect was in a dose-dependent manner. After the liver metastasis was formed, Adv-p53 was administered intraportally. The liver weight in the Adv-p53 treated mice on day 5 group (1.22 +/- 0.09 g) was significantly less than that in the Adv-CMV group (3.98 +/- 1.01 g , P < 0.05). The number of metastatic nodules in the Adv-p53 treaed mice on day 5 group (5.5 +/- 3.5) was significantly less than that in the Adv-CMV group (113.2 +/- 5.8, P < 0.05). Repeatedly intraportal administration of Adv-p53 could enhance this anti-tumor effect.

CONCLUSIONLocal administration of Adv-p53 into the portal system would be a useful strategy for the liver metastasis treatment.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Female ; Fibrosarcoma ; pathology ; Genetic Therapy ; Liver Neoplasms, Experimental ; secondary ; therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Recombinant Proteins ; genetics ; therapeutic use ; Tumor Suppressor Protein p53 ; administration & dosage ; genetics ; therapeutic use