AIM: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.METHODS: Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) an...AIM: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.METHODS: Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay.RESULTS: There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P＜0.001). HCC children (n=21) in Fusui county had a higher level of hOGG1(P＜0.01) and a lower level of 8-oxoG (P＜0.05) than the controls (n=63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P＜0.05)than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele.CONCLUSION: This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.展开更多
AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP befor...AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liver damage were investigated. The changes in adenosine concentration in hepatic tissue and those of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed.RESULTS: Recipients with IP significantly improved their one-week survival rate and liver function, they had increased levels of circulating NO and hepatic adenosine, and a reduced level of serum TNF, as compared to controls. Histological changes indicating hepatic injuries appeared improved in the IP group compared with those in control group. The protective effect of IP was also obtained by administration of adenosine,while blockage of the NO pathway using Nco-nitro-L-arginine methyl ester abolished the protective effect of IP.CONCLUSION: IP appears to have a protective effect on the long-term preservation of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in this process.展开更多
AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence o...AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs. GM-CSF+IL-4-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs to ascertain whether NF-κB decoy ODNs might prevent DC maturation. GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were treated with LPS for 18 h to determine whether NF-κB decoy ODNs could prevent LPS-induced IL-12 production in DCs. NF-κB binding activities, costimulatory molecule (CD40, CD80, CD86) surface expression, IL-12 protein expression and allostimulatory capacity of DCs were measured with electrophoretic mobility shift assay (ENSA),flow cytometry, Western blotting, and mixed lymphocyte reaction (MLR), respectively. GM-CSF-propagated DCs, GM-CSF+IL-4 -propagated DCs, and GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were injected intravenously into recipient LEW rats 7 d prior to liver transplantation and immediately after liver transplantation.Histological grading of liver graft rejection was determined 7 d after liver transplantation. Expression of IL-2, IL-4 and IFN-γ, mRNA in liver graft and in recipient spleen was analyzed by semiquantitative RT-PCR. Apoptosis of liver allograft-infiltrating cells was measured with TUNEL staining.RESULTS: GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs-propagated DCs and GM-CSF+ scrambled ODNs-propagated DCs exhibited features of immature DCs, with similar low level of costimulatory molecule(CD40, CD80,CD86) surface expression, absence of NF-κB activation,and few allocostimulatory activities. GM-CSF+IL-4-propagated DCs displayed features of mature DCs, with high levels of costimulatory molecule (CD40, CD80, CD86) surface expression, marked NF-κB activation, and significant allocostimulatory activity. NF-κB decoy展开更多
AIM: To investigate the incidence and treatment of hepatic artery complications after orthotopic liver transplantation.METHODS: From February 1999 to May 2002, orthotopic liver transplantations (OLT) were performed in...AIM: To investigate the incidence and treatment of hepatic artery complications after orthotopic liver transplantation.METHODS: From February 1999 to May 2002, orthotopic liver transplantations (OLT) were performed in 72 patients with end-stage liver diseases with an average age of 40.2±13.6years (ranged from 11 to 68 years), 56 were males and 16 females. The preoperative evaluation for the 72 patients was performed using duplexsonography, abdominal CT scan,and angiography of the hepatic artery. All donor grafts were perfused and preserved in University of Wisconsin solution at 4 ℃. OLT was performed with standard techniques with or without a veno-venous bypass. Reconstructions of hepatic artery were performed between the branch patches of gastroduodenal/hepatic or splenic/common hepatic artery confluence of the donors and recipients, and an end-to-end anastomosis between other arterial vessels of the donors and recipients was done. Arterial anastomosis was performed with interrupted 7-0/8-0 monofilament polypropylene suture under 3.5 x loupe magnification. Diagnosis of the complications of hepatic artery after OLT was based on the clinical presentations, ultrasound findings and arterial angiography. All patients were followed up regularly for duplex ultrasound scan after discharge.RESULTS: The overall incidence of arterial complications in 72 patients after OLTs was 1.4 % (1/72). One 3 cm pseudoaneurysm at the side of anastomotic site of hepatic artery was found by urgent arteriogram due to hemoperitoneum secondary to bile leakage after OLT.Subsequently the pseudoaneurysm was successfully embolized and the blood flow toward the donor liver in hepatic artery remained. The overall postoperative 30-day mortality rate was 8.33 %. The one-year survival rate was 83.72 % in 50 patients with benign diseases and was 71.43 % in 22 patients with malignant diseases following OLT. No death associated with complications of hepatic artery occurred.CONCLUSION: Careful preoperative evaluations and intraoperative microsurgical展开更多
基金the Guangxi Natural Sciences Grant,No.GKZ9912028 and No.GKJ0236030Guangxi Educational Committee Grant,No.GZBH 2000-272+1 种基金Guangxi Health Ministry Medicine Grant,No.Z2001087Singapore Science Grant,No.R-186-000-044-213
文摘AIM: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.METHODS: Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay.RESULTS: There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P＜0.001). HCC children (n=21) in Fusui county had a higher level of hOGG1(P＜0.01) and a lower level of 8-oxoG (P＜0.05) than the controls (n=63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P＜0.05)than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele.CONCLUSION: This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.
基金Supported by the National Natural Science Foundation of China,No.30200278 China Postdoctoral Science Foundation,No.2001-5
文摘AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liver damage were investigated. The changes in adenosine concentration in hepatic tissue and those of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed.RESULTS: Recipients with IP significantly improved their one-week survival rate and liver function, they had increased levels of circulating NO and hepatic adenosine, and a reduced level of serum TNF, as compared to controls. Histological changes indicating hepatic injuries appeared improved in the IP group compared with those in control group. The protective effect of IP was also obtained by administration of adenosine,while blockage of the NO pathway using Nco-nitro-L-arginine methyl ester abolished the protective effect of IP.CONCLUSION: IP appears to have a protective effect on the long-term preservation of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in this process.
基金Supported by the Postdoctoral Science Foundation of China,No.2003033531
文摘AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs. GM-CSF+IL-4-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs to ascertain whether NF-κB decoy ODNs might prevent DC maturation. GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were treated with LPS for 18 h to determine whether NF-κB decoy ODNs could prevent LPS-induced IL-12 production in DCs. NF-κB binding activities, costimulatory molecule (CD40, CD80, CD86) surface expression, IL-12 protein expression and allostimulatory capacity of DCs were measured with electrophoretic mobility shift assay (ENSA),flow cytometry, Western blotting, and mixed lymphocyte reaction (MLR), respectively. GM-CSF-propagated DCs, GM-CSF+IL-4 -propagated DCs, and GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were injected intravenously into recipient LEW rats 7 d prior to liver transplantation and immediately after liver transplantation.Histological grading of liver graft rejection was determined 7 d after liver transplantation. Expression of IL-2, IL-4 and IFN-γ, mRNA in liver graft and in recipient spleen was analyzed by semiquantitative RT-PCR. Apoptosis of liver allograft-infiltrating cells was measured with TUNEL staining.RESULTS: GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs-propagated DCs and GM-CSF+ scrambled ODNs-propagated DCs exhibited features of immature DCs, with similar low level of costimulatory molecule(CD40, CD80,CD86) surface expression, absence of NF-κB activation,and few allocostimulatory activities. GM-CSF+IL-4-propagated DCs displayed features of mature DCs, with high levels of costimulatory molecule (CD40, CD80, CD86) surface expression, marked NF-κB activation, and significant allocostimulatory activity. NF-κB decoy
文摘AIM: To investigate the incidence and treatment of hepatic artery complications after orthotopic liver transplantation.METHODS: From February 1999 to May 2002, orthotopic liver transplantations (OLT) were performed in 72 patients with end-stage liver diseases with an average age of 40.2±13.6years (ranged from 11 to 68 years), 56 were males and 16 females. The preoperative evaluation for the 72 patients was performed using duplexsonography, abdominal CT scan,and angiography of the hepatic artery. All donor grafts were perfused and preserved in University of Wisconsin solution at 4 ℃. OLT was performed with standard techniques with or without a veno-venous bypass. Reconstructions of hepatic artery were performed between the branch patches of gastroduodenal/hepatic or splenic/common hepatic artery confluence of the donors and recipients, and an end-to-end anastomosis between other arterial vessels of the donors and recipients was done. Arterial anastomosis was performed with interrupted 7-0/8-0 monofilament polypropylene suture under 3.5 x loupe magnification. Diagnosis of the complications of hepatic artery after OLT was based on the clinical presentations, ultrasound findings and arterial angiography. All patients were followed up regularly for duplex ultrasound scan after discharge.RESULTS: The overall incidence of arterial complications in 72 patients after OLTs was 1.4 % (1/72). One 3 cm pseudoaneurysm at the side of anastomotic site of hepatic artery was found by urgent arteriogram due to hemoperitoneum secondary to bile leakage after OLT.Subsequently the pseudoaneurysm was successfully embolized and the blood flow toward the donor liver in hepatic artery remained. The overall postoperative 30-day mortality rate was 8.33 %. The one-year survival rate was 83.72 % in 50 patients with benign diseases and was 71.43 % in 22 patients with malignant diseases following OLT. No death associated with complications of hepatic artery occurred.CONCLUSION: Careful preoperative evaluations and intraoperative microsurgical
