BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron ov...AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD,including 59 with non-alcoholic steatohepatitis (NASH),22 with alcoholic liver disease (ALD),19 of cirrhosis due to viruses (HBV,HCV),and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations. RESULTS:Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals,14.8% in 236 patients (16.9% in NASH,13.6% in ALD,26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.CONCLUSION:Primary iron overload in Indians is nonHFE type,which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.展开更多
BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual c...BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β).Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway.In this study,we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of HCC.METHODS:Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3,Smad4,pSmad3C (S423/425),pSmad3L (T179),pSmad3L (S204),and pSmad3L (S213).Disease-specific death was defined as 1) tumor occupying more than 80% of the liver,2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation,3) obstructive jaundice due to tumor,4) distant metastases,or 5) variceal hemorrhage with PVTT proximal to the first bifurcation.At the time of analysis,tumor recurrence was detected in 184 (67.6%) patients,and 96 (35.3%) had died of HCC.RESULTS:Nuclear and cytoplasmic localization of Smad3,and nuclear localization of Smad4 were observed in 18.0%,9.9%,and 9.2% of HCCs,respectively.The rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation:pSmad3C (S423/425) 8.1%,pSmad3L (T179) 2.6%,pSmad3L (S204) 2.2%,and pSmad3L (S213) 10.3%.Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free survival.pSmad3L (S213) (P=0.006),intrahepatic metastasis,multicentric occurrence,and liver cirrhosis were independent predictors of shorter recurrence- free survival.Cytoplasmic Smad3 (P=0.006),larger tumor size,and intrahepatic metastasis were independent predictors of shorter disease-specific survival.Only pSmad3L (S213) did not show an unfavorable influence on recurrence-free survival (P=0.331) on univariate analysis.CONCLUSIONS:pSmad3C (S423/425),pSmad3L (S213),and Smad3 may be predictors of prognosis in HCC patients after curative hepatectomy.pSmad3C (S423/425) and pSmad3L (S213) may be used as immunohistochemical biomarkers to identify patients with a high risk of recurrence.展开更多
The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus we...The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus were used as probes to test the photokilling activities of the nanoparticles. The toxicity effects of TiO2 nanoparticles on the environment were determined by a standard test using gram-negative bioluminescent bacteria Vibrio fischeri. The antimicrobial activity of these nanoparticles (NPs) was then investigated versus NPs concentration, UV irradiation time and micro- organism strains. We evaluated the LC50 values of the nanoparticles suspension by counting the Colony-Forming Units. Results highlighted the differences in bacteria sensitivity facing photokilling treatment induced by the irradiation of anatase TiO2 nanoparticles suspension. At the concentration of 1 g·L-1 TiO2, tested bacteria were killed after 30 minutes of photo-treatment. Using different TiO2 concentrations, the Staphylococcus aureus gram-positive/catalase-positive bacteria were more resistant than gram-negative/catalase-positive ones or gram-positive/catalase-negative bacteria. An effect of UV irradiation was evaluated by the quantification of hydrogen peroxide generated by the photolysis of water molecules in presence of the nanoparticles with or without the most resistant bacterium (S. aureus). After 30 minutes with UV irradiation in these two conditions, the concentration of hydrogen peroxide was 35 μM in presence of 1.2 g·L-1 TiO2 suspension. This result suggested that the resistance mechanism of S. aureus was not due to an extracelullar H2O2 enzymatic degradation.展开更多
随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散...随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散及斜率尽可能低,从而使色散管理成本降到最低的新型单模光纤.我们设计和计算了这种新型的光纤的结构并对其性能参数进行了分析和讨论.展开更多
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
基金a grant from the Department of Biotechnology, India
文摘AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD,including 59 with non-alcoholic steatohepatitis (NASH),22 with alcoholic liver disease (ALD),19 of cirrhosis due to viruses (HBV,HCV),and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations. RESULTS:Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals,14.8% in 236 patients (16.9% in NASH,13.6% in ALD,26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.CONCLUSION:Primary iron overload in Indians is nonHFE type,which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.
文摘BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β).Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway.In this study,we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of HCC.METHODS:Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3,Smad4,pSmad3C (S423/425),pSmad3L (T179),pSmad3L (S204),and pSmad3L (S213).Disease-specific death was defined as 1) tumor occupying more than 80% of the liver,2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation,3) obstructive jaundice due to tumor,4) distant metastases,or 5) variceal hemorrhage with PVTT proximal to the first bifurcation.At the time of analysis,tumor recurrence was detected in 184 (67.6%) patients,and 96 (35.3%) had died of HCC.RESULTS:Nuclear and cytoplasmic localization of Smad3,and nuclear localization of Smad4 were observed in 18.0%,9.9%,and 9.2% of HCCs,respectively.The rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation:pSmad3C (S423/425) 8.1%,pSmad3L (T179) 2.6%,pSmad3L (S204) 2.2%,and pSmad3L (S213) 10.3%.Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free survival.pSmad3L (S213) (P=0.006),intrahepatic metastasis,multicentric occurrence,and liver cirrhosis were independent predictors of shorter recurrence- free survival.Cytoplasmic Smad3 (P=0.006),larger tumor size,and intrahepatic metastasis were independent predictors of shorter disease-specific survival.Only pSmad3L (S213) did not show an unfavorable influence on recurrence-free survival (P=0.331) on univariate analysis.CONCLUSIONS:pSmad3C (S423/425),pSmad3L (S213),and Smad3 may be predictors of prognosis in HCC patients after curative hepatectomy.pSmad3C (S423/425) and pSmad3L (S213) may be used as immunohistochemical biomarkers to identify patients with a high risk of recurrence.
文摘The aim of this work was to evaluate the photokilling efficiency of synthesized titanium dioxide nanoparticles in suspension. Two strains of Escherichia coli, Lactobacillus casei rhamnosus and Staphylococcus aureus were used as probes to test the photokilling activities of the nanoparticles. The toxicity effects of TiO2 nanoparticles on the environment were determined by a standard test using gram-negative bioluminescent bacteria Vibrio fischeri. The antimicrobial activity of these nanoparticles (NPs) was then investigated versus NPs concentration, UV irradiation time and micro- organism strains. We evaluated the LC50 values of the nanoparticles suspension by counting the Colony-Forming Units. Results highlighted the differences in bacteria sensitivity facing photokilling treatment induced by the irradiation of anatase TiO2 nanoparticles suspension. At the concentration of 1 g·L-1 TiO2, tested bacteria were killed after 30 minutes of photo-treatment. Using different TiO2 concentrations, the Staphylococcus aureus gram-positive/catalase-positive bacteria were more resistant than gram-negative/catalase-positive ones or gram-positive/catalase-negative bacteria. An effect of UV irradiation was evaluated by the quantification of hydrogen peroxide generated by the photolysis of water molecules in presence of the nanoparticles with or without the most resistant bacterium (S. aureus). After 30 minutes with UV irradiation in these two conditions, the concentration of hydrogen peroxide was 35 μM in presence of 1.2 g·L-1 TiO2 suspension. This result suggested that the resistance mechanism of S. aureus was not due to an extracelullar H2O2 enzymatic degradation.
文摘随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散及斜率尽可能低,从而使色散管理成本降到最低的新型单模光纤.我们设计和计算了这种新型的光纤的结构并对其性能参数进行了分析和讨论.
