Objective: To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods: The in vitro cultured HepG2 lines were treated with various concentrations of cigl...Objective: To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods: The in vitro cultured HepG2 lines were treated with various concentrations of ciglitazone. The in vitro growth of HepG2 cells was examined by growth curve and the cell cycle was analyzed by flow cytometry. HepG2 cells (1×10^6 /mouse) were inoculated subcutaneously into 20 nude mice to establish the hepatocellular carcinoma model. The mice were randomly divided into two groups: the control group (group A, n=10) and the ciglitazone-treated group (group B, n=10). The mice in the group B were injected with 100μL (100μmol/L) of ciglitazone every other day for 15 times, while the mice in the group A with saline instead. One month later, the weights of the resected subcutaneous tumors and suppression rates were measured. The expression of cyclinD1 and P21 was detected by Western blot. Results: The proliferation of HepG2 was significantly inhibited by ciglitazone in a dose- and timedependant manner. There were more cells arrested in G1/G0 phase and the expression of PPARγ was markedly up-regulated in HepG2 cells treated with ciglitazone. After the treatment with ciglitazone, the average weights of the tumors in the group A and B were 3.73±0.22 g and 2.60±0.35 g, respectively, and the tumor suppression rate in the group B was 30%. The expression of cyclinD1 was increased significantly, while that of P21 was decreased significantly in group A as compared with that in group B. Conclusion: Ciglitazone could significantly inhibit HepG2 proliferation in a dose- and time-dependent manner, and induce differentiation of HepG2, the mechanism of which may be related to the PPARγ intervention to cell cycle control.展开更多
OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory ef...OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory effect of As2O3 on HepG2 cells at various As2O3 concentrations. The expression of p-JNK, caspase-3 and PARP was detected by Western blots. RESULTS As2O3 markedly inhibited the growth of the HepG2 cells and induced apoptosis. The results of Western blot analysis showed that the As2O3-induced apoptosis was accompanied by caspase-3 and PARP activation. p-JNK was detected at 10 min following As2O3 treatment, and preceded to peak at 20 min, and decreased by 30 min. The total protein content did not obviously change. The activation of JNK occurred prior to cell apoptosis. SP600125, a JNK inhibitor, suppressed the As2O3-induced activation of caspase-3 and PARP cleavage. CONCLUSION As2O3 inhibits the proliferation of human HepG2 hepatocellular carcinoma cells by inducing apoptosis in vitro. As2O3-induced apoptosis is accessed through the caspase-3 pathway. The JNK signal-transduction pathway and caspase-3 are involved upstream in the As2O3 induced HepG2 apoptotic response.展开更多
AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope ...AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.展开更多
AIM: To investigate the therapeutic effects of resveratrol (RESV) as a free radical scavenger on experimental severe acute pancreatitis (SAP). METHODS: Seventy-two male Sprague-Dawley rats were divided randomly ...AIM: To investigate the therapeutic effects of resveratrol (RESV) as a free radical scavenger on experimental severe acute pancreatitis (SAP). METHODS: Seventy-two male Sprague-Dawley rats were divided randomly into sham operation group, SAP group, and resveratrol-treated group. Pancreatitis was induced by intraductal administration of 0.1 mL/kg 4% sodium taurocholate. RESV was given intravenously at a dose of 20 mg/kg body weight. All animals were killed at 3, 6, 12 h after induction of the model. Serum amylase, pancreatic superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) were determined. Pathologic changes of the pancreas were observed under optical microscope. RESULTS: The serum amylase, pancreatic MPO and the score of pathologic damage increased after the induction of pancreatitis, early (3, 6 h) SAP samples were characterized by decreased pancreatic SOD and increased pancreatic MDA. Resveratrol exhibited a protective effect against lipid peroxidation in cell membrane caused by oxygen free radicals in the early stage of SAP. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by lower serum amylase, less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. CONCLUSION: RESV may exert its therapeutic effect on SAP by lowering pancreatic oxidative free radicals and reducing pancreatic tissue infiltration of neutrophils.展开更多
A female patient at the age of 17 received dilator implant on the right part of her face to prepare skin flap for her facial scar.The skin flap was in good conditions before scar cutting,but showed poor blood circulat...A female patient at the age of 17 received dilator implant on the right part of her face to prepare skin flap for her facial scar.The skin flap was in good conditions before scar cutting,but showed poor blood circulation after being transferred.Hyperbaric oxygen therapy was given at 0.2 MPa(2ATA) in double pure oxygen cabins for 90 min every day for 10 d.The skin flap showed in sound viability and sound blood circulation after the treatment.Hyperbaric oxygen therapy can be used to treat blood circulation disorder in transferred skin flap.展开更多
We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine my...We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine myelinolysis following living donor liver transplantation from January 2005 to November 2007 were retrospectively analyzed at the West China Hospital, Sichuan University, China. The three patients developed hyponatremia prior to surgery. Case 1 suffered locked-in syndrome following surgery, and received a large dose of gamma globulin, and subsequently recovered. Case 2 was in a coma for three days, and received hyperbaric chamber treatment. This patient remained in a mild coma for six months following surgery. Case 3 developed consciousness disturbances, gradually went into a coma following surgery, and died due to pulmonary infection. Central pontine myelinolysis is a severe complication in patients following living donor liver transplantation. Large-dose gamma globulin treatment, as well as hyperbaric oxygen, might be effective therapeutic methods.展开更多
AIM: TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METH...AIM: TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METHODS: Expressions of PPARy and retinoid acid receptor (RXRα) were examined by reverse-transcription polymerase chain reaction (RT-PCR) with immunocyto- chemical staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy-△12,14 prostaglandin J2 (15d-PGJ2), a ligand of PPART, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium (MTT) assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARy, was administered via water drinking in experimental group of nude mice. After 75 d, all mice were sacrificed. Expression of proliferating cell nuclear antigen (PCNA) in tumor tissue was examined with immunohistochemical staining. Expression of vascular endothelial growth factor (VEGF) mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosi- glitazone on changes of microvascular density (MVD) and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immu- nohistochemistry staining labeled with anti-Ⅳ collagen antibody, and indicated by MVD. RESULTS: RT-PCR and immunocytochemical stain- ing showed that PPARγ and RXRα were expressed in PANC-1 cells at both transcription level and translation level. MTT assay demonstrated that 15d-PGJ2, 9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a com- bined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carcinoma as compared to control group (0.48 ± 0.23 cm^3 vs 2.488 ± 0.59 cm^3, P 〈 0.05), and the growth inhibition rate was 80.7%. Immuno- histochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group. 15d-PGJ2, 9-cis-RA and their com- bination inhibited the expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD was decreased more significantly in Rosiglitazone- treated mice (10.67±3.07) than in the control group (31.44±6.06) (P 〈 0.01). VEGF expression in xeno- graft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION: Activation of PPARγ, inhibits the growth of pancreatic carcinoma both in vitro and in vivo. Sup- pression of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγ, activation inhibits the growth of pancre- atic carcinoma.展开更多
Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Anti...Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008. All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insuffi cient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefi ts of antioxidants in islet isolation procedures cannot be ignored.展开更多
Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a ...Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.展开更多
AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cu...AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase- mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS: Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. CONCLUSION: PPARγ ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.展开更多
AIM: To evaluate the effectiveness of mastic administra-tion on the clinical course and plasma inflammatory me-diators of patients with active Crohn’s disease (CD).METHODS: This pilot study was conducted in patients ...AIM: To evaluate the effectiveness of mastic administra-tion on the clinical course and plasma inflammatory me-diators of patients with active Crohn’s disease (CD).METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attend-ing the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Ac-tivity Index (CDAI), Nutritional Risk Index (NRI), C-re-active protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P < 0.05 was considered to indicate statistical significance.RESULTS: Patients exhibited significant reduction of CDAI (222.9 ± 18.7 vs 136.3 ± 12.3, P = 0.05) as com-pared to pretreament values. Plasma IL-6 was signifi-cantly decreased (21.2 ± 9.3 pg/mL vs 7.2 ± 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 ± 13.1 mg/mL vs 19.7 ± 5.5, P = 0.028). TAP was significantly increased (0.15 ± 0.09 vs 0.57 ± 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic signifi-cantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately ac-tive CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.展开更多
AIM: To clarify the effectiveness of CO2 insufflation in potentially difficult colonoscopy cases, particularly in relation to the experience level of colonoscopists. METHODS: One hundred twenty potentially difficult...AIM: To clarify the effectiveness of CO2 insufflation in potentially difficult colonoscopy cases, particularly in relation to the experience level of colonoscopists. METHODS: One hundred twenty potentially difficult cases were included in this study, which involved females with a low body mass index and patients with earlier abdominal and/or pelvic open surgery or previously diagnosed left-side colon diverticulosis. Patients receiving colonoscopy examinations without sedation using a pediatric variable-stiffness colonoscope were divided into two groups based on either CO2 or standard air insuffiation. Both insufflation procedures were also evaluated according to the experience level of the respective colonoscopists who were divided into an experienced colonoscopist (EC) group and a less experienced colonoscopist (LEC) group. Study measurements included a 100-mm visual analogue scale (VAS) for patient pain during and after colonoscopy examinations, in addition to insertion to the cecum and withdrawal times. RESULTS: Examination times did not differ, however, VAS scores in the CO2 group were significantly better than in the air group (P〈 0.001, two-way ANOVA) from immediately after the procedure and up to 2 h later. There were no significant differences between either insufflation method in the EC group (P = 0.29), however, VAS scores for CO2 insufflation were significantly better than air insufflation in the LEC group (P = 0.023) immediately after colonoscopies and up to 4 h afterwards. CONCLUSION: CO2 insufflation reduced patient pain after colonoscopy in potentially difficult cases when performed by LECs.展开更多
AIM: To determine the effects of prophylactic peroxisome proliferator-activated receptor (PPARy) agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography (post-ERCP) ...AIM: To determine the effects of prophylactic peroxisome proliferator-activated receptor (PPARy) agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography (post-ERCP) acute pancreatitis. METHODS: Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS: Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity (MPO) in pancreas. This result correlated with the activation of nuclear factor κB (NFκB) and the inducible NO synthase (iNOS) expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression. CONCLUSION: A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.展开更多
AIM: To demonstrate the ^18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in patients with non-Hodgkin's lymphoma (NHL) involving the gastrointestinal (GI) tract and the clinical util...AIM: To demonstrate the ^18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in patients with non-Hodgkin's lymphoma (NHL) involving the gastrointestinal (GI) tract and the clinical utility of modality despite of the known normal uptake of FDG in the GI tract. METHODS: Thirty-three patients with biopsy-proven gastrointestinal NHL who had undergone FDG-PET scan were induded. All the patients were injected with 10-15 mCJ FDG and scanned approximately 60 min later with a CTI/ Siemens HR (+) PET scanner. PET scans were reviewed and the maximum standard uptake value (SUVmax) of the lesions was measured before and after the treatment, if data were available and compared with histologic diagnoses. RESULTS: Twenty-five patients had a high-grade lymphoma and eight had a low-grade lymphoma. The stomach was the most common site of the involvement (20 patients). In high-grade lymphoma, PET showed focal nodular or diffuse hypermetabolic activity. The average SUVmax+SD was 11.58±5.83. After the therapy, the patients whose biopsies showed no evidence of lymphoma had a lower uptake without focal lesions. The SUVmax+SD decreased from 11.58±5.83 to 2.21± 0.78. in patients whose post-treatment biopsies showed lymphoma, the SUVmax+SD was 9.42±6.27. Low-grade follicular lymphomas of the colon and stomach showed diffuse hypermetabolic activity in the bowel wall (SUVmax= 8.2 and 10.3, respectively). The SUVmax was 2.02-3.8 (mean 3.02) in the stomach lesions of patients with MALT lymphoma. CONCLUSION: ^18F-FDG PET contributes to the diagnosis of high-grade gastrointestinal non-Hodgldn's lymphoma, even when there is the normal background FDG activity. Furthermore, the SUV plays a role in evaluating treatment response. Low-grade NHL demonstrates FDG uptake but at a lesser intensity than seen in high-grade NHL.展开更多
AIM: To investigate the relationship between cycloo- xygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), and to determine the clinical significance of this relationship in esophageal cancer patient...AIM: To investigate the relationship between cycloo- xygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma (ESCC) who were undergoing preoperative CRT. RESULTS: Fourteen out of 40 ESCC patients showed a pathological complete response (CR) after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression (P 〈 0.05). There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement (P = 0.0277 and P = 0.0095, respectively). COX-2 expression and VEGF expression had significant prognostic value for disease-free survival (log-rank test; P = 0.0073 and P = 0.0341, respectively), but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.展开更多
Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Mothoda Totally 100 young male army members newly recruited from Sichuan province (4...Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Mothoda Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups: 50 in aminophylline group (A group) and 50 in control group ( C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it. Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system. Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H202, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P 〈0. 01 ) ; and NO, SO2 , PaO2 decreased more markedly in C group ( P 〈 0. 05 for NO, P 〈 0. 0001 for SO2 and PaO2 ). Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.展开更多
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of ...Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.展开更多
文摘Objective: To study the effect of ciglitazone on hepatic cancer cells HepG2 growth in vitro and in vivo and its mechanisms. Methods: The in vitro cultured HepG2 lines were treated with various concentrations of ciglitazone. The in vitro growth of HepG2 cells was examined by growth curve and the cell cycle was analyzed by flow cytometry. HepG2 cells (1×10^6 /mouse) were inoculated subcutaneously into 20 nude mice to establish the hepatocellular carcinoma model. The mice were randomly divided into two groups: the control group (group A, n=10) and the ciglitazone-treated group (group B, n=10). The mice in the group B were injected with 100μL (100μmol/L) of ciglitazone every other day for 15 times, while the mice in the group A with saline instead. One month later, the weights of the resected subcutaneous tumors and suppression rates were measured. The expression of cyclinD1 and P21 was detected by Western blot. Results: The proliferation of HepG2 was significantly inhibited by ciglitazone in a dose- and timedependant manner. There were more cells arrested in G1/G0 phase and the expression of PPARγ was markedly up-regulated in HepG2 cells treated with ciglitazone. After the treatment with ciglitazone, the average weights of the tumors in the group A and B were 3.73±0.22 g and 2.60±0.35 g, respectively, and the tumor suppression rate in the group B was 30%. The expression of cyclinD1 was increased significantly, while that of P21 was decreased significantly in group A as compared with that in group B. Conclusion: Ciglitazone could significantly inhibit HepG2 proliferation in a dose- and time-dependent manner, and induce differentiation of HepG2, the mechanism of which may be related to the PPARγ intervention to cell cycle control.
基金supported by a grant from theNational Natural Science Foundation of China(No.30572114).
文摘OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory effect of As2O3 on HepG2 cells at various As2O3 concentrations. The expression of p-JNK, caspase-3 and PARP was detected by Western blots. RESULTS As2O3 markedly inhibited the growth of the HepG2 cells and induced apoptosis. The results of Western blot analysis showed that the As2O3-induced apoptosis was accompanied by caspase-3 and PARP activation. p-JNK was detected at 10 min following As2O3 treatment, and preceded to peak at 20 min, and decreased by 30 min. The total protein content did not obviously change. The activation of JNK occurred prior to cell apoptosis. SP600125, a JNK inhibitor, suppressed the As2O3-induced activation of caspase-3 and PARP cleavage. CONCLUSION As2O3 inhibits the proliferation of human HepG2 hepatocellular carcinoma cells by inducing apoptosis in vitro. As2O3-induced apoptosis is accessed through the caspase-3 pathway. The JNK signal-transduction pathway and caspase-3 are involved upstream in the As2O3 induced HepG2 apoptotic response.
文摘AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation,such as diameters of arterioles and venules,velocity of RBCs in venules,leukocyte rolling,adhesion and emigration,free radicals released from post-capillary venules,FITC- albumin leakage and mast cell degranulation,were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile,the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils,and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation,including a significant increase in the positive region of venulestained with Monastral blue B,rolling and adhesion of leukocytes,production of oxygen radical in venular wall,albumin efflux and enhanced mast cell degranulation in vivo,all of which,except for the leukocyte rolling,were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils,and the expression of ICAM-1 in HUVECs were increased by exposure to LPS,and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.
文摘AIM: To investigate the therapeutic effects of resveratrol (RESV) as a free radical scavenger on experimental severe acute pancreatitis (SAP). METHODS: Seventy-two male Sprague-Dawley rats were divided randomly into sham operation group, SAP group, and resveratrol-treated group. Pancreatitis was induced by intraductal administration of 0.1 mL/kg 4% sodium taurocholate. RESV was given intravenously at a dose of 20 mg/kg body weight. All animals were killed at 3, 6, 12 h after induction of the model. Serum amylase, pancreatic superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) were determined. Pathologic changes of the pancreas were observed under optical microscope. RESULTS: The serum amylase, pancreatic MPO and the score of pathologic damage increased after the induction of pancreatitis, early (3, 6 h) SAP samples were characterized by decreased pancreatic SOD and increased pancreatic MDA. Resveratrol exhibited a protective effect against lipid peroxidation in cell membrane caused by oxygen free radicals in the early stage of SAP. This attenuation of the redox state impairment reduced cellular oxidative damage, as reflected by lower serum amylase, less severe pancreatic lesions, normal pancreatic MDA levels, as well as diminished neutrophil infiltration in pancreas. CONCLUSION: RESV may exert its therapeutic effect on SAP by lowering pancreatic oxidative free radicals and reducing pancreatic tissue infiltration of neutrophils.
文摘A female patient at the age of 17 received dilator implant on the right part of her face to prepare skin flap for her facial scar.The skin flap was in good conditions before scar cutting,but showed poor blood circulation after being transferred.Hyperbaric oxygen therapy was given at 0.2 MPa(2ATA) in double pure oxygen cabins for 90 min every day for 10 d.The skin flap showed in sound viability and sound blood circulation after the treatment.Hyperbaric oxygen therapy can be used to treat blood circulation disorder in transferred skin flap.
文摘We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine myelinolysis following living donor liver transplantation from January 2005 to November 2007 were retrospectively analyzed at the West China Hospital, Sichuan University, China. The three patients developed hyponatremia prior to surgery. Case 1 suffered locked-in syndrome following surgery, and received a large dose of gamma globulin, and subsequently recovered. Case 2 was in a coma for three days, and received hyperbaric chamber treatment. This patient remained in a mild coma for six months following surgery. Case 3 developed consciousness disturbances, gradually went into a coma following surgery, and died due to pulmonary infection. Central pontine myelinolysis is a severe complication in patients following living donor liver transplantation. Large-dose gamma globulin treatment, as well as hyperbaric oxygen, might be effective therapeutic methods.
文摘AIM: TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METHODS: Expressions of PPARy and retinoid acid receptor (RXRα) were examined by reverse-transcription polymerase chain reaction (RT-PCR) with immunocyto- chemical staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy-△12,14 prostaglandin J2 (15d-PGJ2), a ligand of PPART, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium (MTT) assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARy, was administered via water drinking in experimental group of nude mice. After 75 d, all mice were sacrificed. Expression of proliferating cell nuclear antigen (PCNA) in tumor tissue was examined with immunohistochemical staining. Expression of vascular endothelial growth factor (VEGF) mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosi- glitazone on changes of microvascular density (MVD) and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immu- nohistochemistry staining labeled with anti-Ⅳ collagen antibody, and indicated by MVD. RESULTS: RT-PCR and immunocytochemical stain- ing showed that PPARγ and RXRα were expressed in PANC-1 cells at both transcription level and translation level. MTT assay demonstrated that 15d-PGJ2, 9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a com- bined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carcinoma as compared to control group (0.48 ± 0.23 cm^3 vs 2.488 ± 0.59 cm^3, P 〈 0.05), and the growth inhibition rate was 80.7%. Immuno- histochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group. 15d-PGJ2, 9-cis-RA and their com- bination inhibited the expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD was decreased more significantly in Rosiglitazone- treated mice (10.67±3.07) than in the control group (31.44±6.06) (P 〈 0.01). VEGF expression in xeno- graft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION: Activation of PPARγ, inhibits the growth of pancreatic carcinoma both in vitro and in vivo. Sup- pression of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγ, activation inhibits the growth of pancre- atic carcinoma.
文摘Islet transplantation as a promising treatment for type 1 diabetes has received widespread attention. Oxidative stress plays an essential role in cell injury during islet isolation and transplantation procedures. Antioxidants have been used in various studies to improve islet transplantation procedures. The present study reviews the role of oxidative stress and the benefits of antioxidants in islet transplantation procedures. The bibliographical databases Pubmed and Scopus were searched up to November 2008. All relevant human and animal in-vivo and in-vitro studies, which investigated antioxidants on islets, were included. Almost all the tested antioxidants used in the in-vitro studies enhanced islet viability and insulin secretion. Better control of blood glucose after transplantation was the major outcome of antioxidant therapy in all in-vivo studies. The data also indicated that antioxidants improved islet transplantation procedures. Although there is still insuffi cient evidence to draw definitive conclusions about the efficacy of individual supplements, the benefi ts of antioxidants in islet isolation procedures cannot be ignored.
文摘Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.
基金Grants from the State Key Basic Research Program, No. 2002CB513100
文摘AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase- mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS: Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. CONCLUSION: PPARγ ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer.
基金Supported by a grant from the Chios Gum Mastic Growers Association
文摘AIM: To evaluate the effectiveness of mastic administra-tion on the clinical course and plasma inflammatory me-diators of patients with active Crohn’s disease (CD).METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attend-ing the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Ac-tivity Index (CDAI), Nutritional Risk Index (NRI), C-re-active protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P < 0.05 was considered to indicate statistical significance.RESULTS: Patients exhibited significant reduction of CDAI (222.9 ± 18.7 vs 136.3 ± 12.3, P = 0.05) as com-pared to pretreament values. Plasma IL-6 was signifi-cantly decreased (21.2 ± 9.3 pg/mL vs 7.2 ± 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 ± 13.1 mg/mL vs 19.7 ± 5.5, P = 0.028). TAP was significantly increased (0.15 ± 0.09 vs 0.57 ± 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic signifi-cantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately ac-tive CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.
基金Supported by The Japanese Foundation for Research and Promotion of Endoscopy (JFE)
文摘AIM: To clarify the effectiveness of CO2 insufflation in potentially difficult colonoscopy cases, particularly in relation to the experience level of colonoscopists. METHODS: One hundred twenty potentially difficult cases were included in this study, which involved females with a low body mass index and patients with earlier abdominal and/or pelvic open surgery or previously diagnosed left-side colon diverticulosis. Patients receiving colonoscopy examinations without sedation using a pediatric variable-stiffness colonoscope were divided into two groups based on either CO2 or standard air insuffiation. Both insufflation procedures were also evaluated according to the experience level of the respective colonoscopists who were divided into an experienced colonoscopist (EC) group and a less experienced colonoscopist (LEC) group. Study measurements included a 100-mm visual analogue scale (VAS) for patient pain during and after colonoscopy examinations, in addition to insertion to the cecum and withdrawal times. RESULTS: Examination times did not differ, however, VAS scores in the CO2 group were significantly better than in the air group (P〈 0.001, two-way ANOVA) from immediately after the procedure and up to 2 h later. There were no significant differences between either insufflation method in the EC group (P = 0.29), however, VAS scores for CO2 insufflation were significantly better than air insufflation in the LEC group (P = 0.023) immediately after colonoscopies and up to 4 h afterwards. CONCLUSION: CO2 insufflation reduced patient pain after colonoscopy in potentially difficult cases when performed by LECs.
基金Supported by FIS grant PI020286 and PI050599 and Ramón y Cajal contract to Emma Folch-Puy. Susana Granell was a recipient for an IDIBAPS grant
文摘AIM: To determine the effects of prophylactic peroxisome proliferator-activated receptor (PPARy) agonist administration in an experimental model of post-endoscopic retrograde cholangiopancreatography (post-ERCP) acute pancreatitis. METHODS: Post-ERCP pancreatitis was induced in male Wistar rats by infusion of contrast medium into the pancreatic duct. In additional group, rosiglitazone, a PPARγ agonist, was administered 1 h before infusion of contrast medium. Plasma and pancreas samples were obtained 6 h after the infusion. RESULTS: Infusion of contrast medium into the pancreatic duct resulted in an inflammatory process characterized by increased lipase levels in plasma, and edema and myeloperoxidase activity (MPO) in pancreas. This result correlated with the activation of nuclear factor κB (NFκB) and the inducible NO synthase (iNOS) expression in pancreatic cells. Rosiglitazone reduced the increase in lipase and the level of edema and the increase in myeloperoxidase as well as the activation of NFκB and iNOS expression. CONCLUSION: A single oral dose of rosiglitazone, given 1 h before post-ERCP pancreatitis induction is effective in reducing the severity of the subsequent inflammatory process. The protective effect of rosiglitazone was associated with NFκB inhibition and the blockage of leukocyte infiltration in pancreas.
文摘AIM: To demonstrate the ^18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) findings in patients with non-Hodgkin's lymphoma (NHL) involving the gastrointestinal (GI) tract and the clinical utility of modality despite of the known normal uptake of FDG in the GI tract. METHODS: Thirty-three patients with biopsy-proven gastrointestinal NHL who had undergone FDG-PET scan were induded. All the patients were injected with 10-15 mCJ FDG and scanned approximately 60 min later with a CTI/ Siemens HR (+) PET scanner. PET scans were reviewed and the maximum standard uptake value (SUVmax) of the lesions was measured before and after the treatment, if data were available and compared with histologic diagnoses. RESULTS: Twenty-five patients had a high-grade lymphoma and eight had a low-grade lymphoma. The stomach was the most common site of the involvement (20 patients). In high-grade lymphoma, PET showed focal nodular or diffuse hypermetabolic activity. The average SUVmax+SD was 11.58±5.83. After the therapy, the patients whose biopsies showed no evidence of lymphoma had a lower uptake without focal lesions. The SUVmax+SD decreased from 11.58±5.83 to 2.21± 0.78. in patients whose post-treatment biopsies showed lymphoma, the SUVmax+SD was 9.42±6.27. Low-grade follicular lymphomas of the colon and stomach showed diffuse hypermetabolic activity in the bowel wall (SUVmax= 8.2 and 10.3, respectively). The SUVmax was 2.02-3.8 (mean 3.02) in the stomach lesions of patients with MALT lymphoma. CONCLUSION: ^18F-FDG PET contributes to the diagnosis of high-grade gastrointestinal non-Hodgldn's lymphoma, even when there is the normal background FDG activity. Furthermore, the SUV plays a role in evaluating treatment response. Low-grade NHL demonstrates FDG uptake but at a lesser intensity than seen in high-grade NHL.
文摘AIM: To investigate the relationship between cycloo- xygenase-2 (COX-2), and vascular endothelial growth factor (VEGF), and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma (ESCC) who were undergoing preoperative CRT. RESULTS: Fourteen out of 40 ESCC patients showed a pathological complete response (CR) after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression (P 〈 0.05). There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement (P = 0.0277 and P = 0.0095, respectively). COX-2 expression and VEGF expression had significant prognostic value for disease-free survival (log-rank test; P = 0.0073 and P = 0.0341, respectively), but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.
文摘Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high- altitude exposure. Mothoda Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups: 50 in aminophylline group (A group) and 50 in control group ( C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it. Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system. Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H202, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P 〈0. 01 ) ; and NO, SO2 , PaO2 decreased more markedly in C group ( P 〈 0. 05 for NO, P 〈 0. 0001 for SO2 and PaO2 ). Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.
文摘Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.