AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-;...AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies.METHODSSerum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSIONSerum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.展开更多
Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly es...Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.展开更多
AIM： To investigate the glutathione-S-transferase M1 （GSTM1） polymorphisms in three Chinese minorities, Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesi...AIM： To investigate the glutathione-S-transferase M1 （GSTM1） polymorphisms in three Chinese minorities, Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.METHODS： A total of 1121 blood samples （442 males and 679 females） were obtained from healthy Kazakh （654）, Uygur （412） and Tajik （55）. Primary esophageal squamous cell cancer （ESCC） tissues from Kazakh were obtained from 116 patients who underwent surgery. GSTM1 polymorphisms were analyzed by a combined approach of PCR and electrophoresis techniques.RESULTS： GSTM1 null genotype was found in 62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of GSTM1 null genotype in Uygur was observed compared with Kazakh （OR： 1.859, 95% CI： 1.445 -2.391, χ^2 = 23.71, P = 0.000）. In addition, GSTM1 null genotype was found in 23.53% of welldifferentiated ESCC in Kazakh, in 49.23% of poorly differentiated ESCC, with a significant difference （OR： 3.152, 95% CI： 1.403-7.080, χ^2 = 8.018, P = 0.007）.CONCLUSION： There is a marked difference in the frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null genotype is associated with differentiation of ESCC in Kazakh.展开更多
Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5&#...Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.展开更多
基金the Poznan University of Medical Sciences Grant,A helping hand(2014)
文摘AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies.METHODSSerum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSIONSerum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.
文摘Objective To elucidate the effect of interleukin-1β （IL- 1β） on human growth hormone （hGH） gene expression in a rat somatotropic pituitary cell line MtT/S. Methods Stably transfected MtT/S cells were firstly established by transfecting 484-Lucl plasmid which contained hGH gene promoter --484 to ＋30 bp and luciferase reporter gene. The effect of IL-1β on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. Results The 10^3 U/mL IL-1β stimulated secretion and synthesis of GH, and promoted the 5＇-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase （MAPKK/MEK） inhibitor PD98059 （40 μmol/L） and p38 mitogen-activated protein kinase （MAPK） inhibitor SB203580 （5 μmol/L） completely blocked the stimulatory effect of IL-1μ, and phosphatidylinositol-3-kinase （PI3-K） inhibitor LY294002 partly abolished the effect of IL-1μ. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit- 1 nor inhibition of Pit- 1 expression affected induction of hGH promoter activity by IL-1μ. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1β, and results showed that the stimulatory effect of IL-1β was abolished following deletion of the --196 to -- 132 bp fragment. Conclusions IL-1β promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1β on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.
基金Supported by a grant from the Xinjiang Science and TechnologyBureau, No. XJKJT200511113 and a grant for 100 YoungExcellent Returned Overseas Chinese Scholars Program, ChineseAcademy of Sciences
文摘AIM： To investigate the glutathione-S-transferase M1 （GSTM1） polymorphisms in three Chinese minorities, Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.METHODS： A total of 1121 blood samples （442 males and 679 females） were obtained from healthy Kazakh （654）, Uygur （412） and Tajik （55）. Primary esophageal squamous cell cancer （ESCC） tissues from Kazakh were obtained from 116 patients who underwent surgery. GSTM1 polymorphisms were analyzed by a combined approach of PCR and electrophoresis techniques.RESULTS： GSTM1 null genotype was found in 62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of GSTM1 null genotype in Uygur was observed compared with Kazakh （OR： 1.859, 95% CI： 1.445 -2.391, χ^2 = 23.71, P = 0.000）. In addition, GSTM1 null genotype was found in 23.53% of welldifferentiated ESCC in Kazakh, in 49.23% of poorly differentiated ESCC, with a significant difference （OR： 3.152, 95% CI： 1.403-7.080, χ^2 = 8.018, P = 0.007）.CONCLUSION： There is a marked difference in the frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null genotype is associated with differentiation of ESCC in Kazakh.
文摘Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.
