AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned t...AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/-展开更多
Background Transforming growth factor beta (TGF β) and matrix metalloproteinases 9 (MMP 9) have been implicated in the pathogenesis of human atherosclerosis but their relationship during lesion progression are poorly...Background Transforming growth factor beta (TGF β) and matrix metalloproteinases 9 (MMP 9) have been implicated in the pathogenesis of human atherosclerosis but their relationship during lesion progression are poorly understood The objective of this study was to investigate the expression of MMP 9, TGF β1 and TGF β receptor Ⅰ (TβR Ⅰ) in human atherosclerotic plaque and their relationship and plaque stability Methods Specimens of human coronary artery atherosclerotic plaques were obtained from 41 patients undergoing coronary endarterectomy, and were paraffin embedded, sectioned at 4 μm intervals then stained with haematoxylin and eosin They were divided into stable (with no or only little lipid core) and unstable plaque groups (with lipid core size>40%): the immunohistochemical staining were performed for MMP 9,TGF β1 and TβR Ⅰ Results The expression of MMP 9 in the unstable plaques was much higher than in the stable ones, but the expression of TGF β1 was higher in the stable plaques There was no similar significant difference for TβR Ⅰ Correlation analysis showed that there was a negative correlation between the expression of MMP 9 and TGF β1 ( r =-0 332, P =0 034 for average areal density; r =-0 373, P = 0 016 for average optical density) Conclusions There were close relationships between MMP 9, TGF β1 and plaque stability Enhanced production of MMP 9 may participate in the formation of unstable plaque, while TGF β1 maybe an important stabilizing factor in preventing transition into an unstable plaque phenotype展开更多
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment ...Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.展开更多
基金Supported by Scientific and Technological Project of Educational Department of Liaoning Province,China,No.L2011166
文摘AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/-
文摘Background Transforming growth factor beta (TGF β) and matrix metalloproteinases 9 (MMP 9) have been implicated in the pathogenesis of human atherosclerosis but their relationship during lesion progression are poorly understood The objective of this study was to investigate the expression of MMP 9, TGF β1 and TGF β receptor Ⅰ (TβR Ⅰ) in human atherosclerotic plaque and their relationship and plaque stability Methods Specimens of human coronary artery atherosclerotic plaques were obtained from 41 patients undergoing coronary endarterectomy, and were paraffin embedded, sectioned at 4 μm intervals then stained with haematoxylin and eosin They were divided into stable (with no or only little lipid core) and unstable plaque groups (with lipid core size>40%): the immunohistochemical staining were performed for MMP 9,TGF β1 and TβR Ⅰ Results The expression of MMP 9 in the unstable plaques was much higher than in the stable ones, but the expression of TGF β1 was higher in the stable plaques There was no similar significant difference for TβR Ⅰ Correlation analysis showed that there was a negative correlation between the expression of MMP 9 and TGF β1 ( r =-0 332, P =0 034 for average areal density; r =-0 373, P = 0 016 for average optical density) Conclusions There were close relationships between MMP 9, TGF β1 and plaque stability Enhanced production of MMP 9 may participate in the formation of unstable plaque, while TGF β1 maybe an important stabilizing factor in preventing transition into an unstable plaque phenotype
文摘Hyperlipidemia is a well-established risk factor for developing cardiovascular disease(CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors(statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein(LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsinkexin type 9(PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.
