Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracosc...Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracoscopic surgery (VATS) was carried out under general anesthesia. A double lumen endobronchial tube was intubated into trachea. One lung ventilation of the healthy side was done during operation. An incision of 8–10 cm long was made along the 4th or 5th intercostals. The lobectomy could be performed under VATS. Radionuclide colloid 32P was injected locally into the area where surgical cleaning of lymph node around was considered to be unsatisfactory or desection of the tumor was not completed. Results: The operation with VEMAST was successful in 29 patients. A conventional lobectomy by thoracotomy had to be done due to unusual bleeding from the pulmonary artery involved during VEMAST in one case and the procedure was interrupted because the pulmonary artery cloud not be separated from the tumor in another patient. There was no dead case or the patient who had any severe complication or adverse response to the radiant. Conclusion: Radionuclide therapy was performed to the treatment of stage II lung cancer with VEMAST in case that surgical resection was considered not to be satisfactory. Minithoractomy assisted with VATS lobectomy and radionuclide colloid 32P therapy is a safe and e?ective technique for some selected stage II lung cancer.展开更多
Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle ce...Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was~25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from~30 kD to~25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.展开更多
In the past,contraction-induced production of reactive oxygen species(ROS)has been implicated in oxidative stress to skeletal muscle.As research advances,clear evidence has revealed a more complete role of ROS under b...In the past,contraction-induced production of reactive oxygen species(ROS)has been implicated in oxidative stress to skeletal muscle.As research advances,clear evidence has revealed a more complete role of ROS under both physiologic and pathologic conditions.Central to the role of ROS is the redox signaling pathways that control exercise-induced major physiologic and cellular responses and adaptations,such as mitochondrial biogenesis,mitophagy,mitochondrial morphologic dynamics,antioxidant defense,and inflammation.The current review focuses on how muscle contraction and immobilization may activate or inhibit redox signalings and their impact on muscle mitochondrial homeostasis and physiologic implications.展开更多
In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Gro...In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.展开更多
Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular di...Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.展开更多
The purpose of this study was to examine the relaxation effect of CY on the vascular smooth muscle (VSM) from rabbits. Experiments were carried out on isolated thoracic aorta of rabbits. CY (3 x 103 mM- 3 mM) coul...The purpose of this study was to examine the relaxation effect of CY on the vascular smooth muscle (VSM) from rabbits. Experiments were carried out on isolated thoracic aorta of rabbits. CY (3 x 103 mM- 3 mM) could relax the VSM preparations pre-contracted by adrenaline (AD), noradrenaline (NE), high-K^+ solution or BaCl2 with respective EC50 values of (0.3 1±0.11) mM, 0.19±0.03 mM, 0.20±0.04 mM and 0.25±0.04 mM. Moreover, CY (10-2 mM, 0.1 mM and 1 mM) inhibited norepinephrine (NE), CaCl2 and KCl-induced vasoconstriction in a concentration dependent manner. The phasic contraction produced by NE was concentration dependently attenuated with CY (10^-2 mM, 0.1 mM and 1 mM) in calcium-free medium, similar to that caused by verapamil. The present findings suggest that CY relaxed thoracic aortic rings by blocking voltage-dependent Ca^2+ channels. The inhibition of intracellular Ca^2+ release may be one of the main vasorelaxant mechanisms of CY.展开更多
文摘Objective: To study the feasibility of radionuclide colloid 32P used for the treatment of stage II lung cancer by video enhanced minimal access muscle sparing thoracotomy (VEMAST). Methods: Video assisted thoracoscopic surgery (VATS) was carried out under general anesthesia. A double lumen endobronchial tube was intubated into trachea. One lung ventilation of the healthy side was done during operation. An incision of 8–10 cm long was made along the 4th or 5th intercostals. The lobectomy could be performed under VATS. Radionuclide colloid 32P was injected locally into the area where surgical cleaning of lymph node around was considered to be unsatisfactory or desection of the tumor was not completed. Results: The operation with VEMAST was successful in 29 patients. A conventional lobectomy by thoracotomy had to be done due to unusual bleeding from the pulmonary artery involved during VEMAST in one case and the procedure was interrupted because the pulmonary artery cloud not be separated from the tumor in another patient. There was no dead case or the patient who had any severe complication or adverse response to the radiant. Conclusion: Radionuclide therapy was performed to the treatment of stage II lung cancer with VEMAST in case that surgical resection was considered not to be satisfactory. Minithoractomy assisted with VATS lobectomy and radionuclide colloid 32P therapy is a safe and e?ective technique for some selected stage II lung cancer.
文摘Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was~25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from~30 kD to~25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.
文摘In the past,contraction-induced production of reactive oxygen species(ROS)has been implicated in oxidative stress to skeletal muscle.As research advances,clear evidence has revealed a more complete role of ROS under both physiologic and pathologic conditions.Central to the role of ROS is the redox signaling pathways that control exercise-induced major physiologic and cellular responses and adaptations,such as mitochondrial biogenesis,mitophagy,mitochondrial morphologic dynamics,antioxidant defense,and inflammation.The current review focuses on how muscle contraction and immobilization may activate or inhibit redox signalings and their impact on muscle mitochondrial homeostasis and physiologic implications.
文摘In order to investigate the role of the Notch signaling pathway in skeletal muscle fibrosis after nerve injury, 60 Sprague-Dawley rats were selected and divided randomly into a control and two experimental groups. Group A served as controls without any treatment. Rats in groups B were injected intraperitoneally with 0.2 mL PBS and those in group C were injected intraperitoneally with 0.2 mL PBS+100 ymol/L, 0.2 mL N-[N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT, a gamma-secretase inhibitor that suppresses Notch signaling) respectively, on postoperative days 1, 3, 7, 10, and 14 in a model of denervation-induced skeletal muscle fibrosis by right sciatic nerve transection. Five rats from each group were euthanized on postoperative days 1, 7, 14, and 28 to collect the right gastrocnemii, and hematoxylin and eosin (HE) staining, immunohistochemistry test, real-time PCR, and Western blotting were performed to assess connective tissue hyperplasia and fibroblast density as well as expression of Notch 1, Jagged 1, and Notch downstream molecules Hes 1 and collagen I (COL I) on day 28. There was no significant difference in HE-stained fibroblast density between group B and C on postoperative day 1. However, fibroblast density was significantly higher in group B than in group C on postoperative days 7, 14, and 28. Notch 1, Jagged 1, Hes 1, and COL I proteins in the gastrocnemius were expressed at very low levels in group A but at high levels in group B. Expression levels of these proteins were significantly lower in group C than in group B (P<0.05), but they were higher in group C than in group A (P<0.05) on postoperative day 28. We are led to conclude that locking the Notch signaling pathway inhibits fibrosis progression of denervated skeletal muscle. Thus, it may be a new approach for treatment of fibrosis of denervated skeletal muscle.
基金This work was supported by National Natural Science Foundation of China (NSFC) (No. 81400265 and No. 81270274), and Peking University People's Hospital Research and Development funds (RDB2014-16).
文摘Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.
文摘The purpose of this study was to examine the relaxation effect of CY on the vascular smooth muscle (VSM) from rabbits. Experiments were carried out on isolated thoracic aorta of rabbits. CY (3 x 103 mM- 3 mM) could relax the VSM preparations pre-contracted by adrenaline (AD), noradrenaline (NE), high-K^+ solution or BaCl2 with respective EC50 values of (0.3 1±0.11) mM, 0.19±0.03 mM, 0.20±0.04 mM and 0.25±0.04 mM. Moreover, CY (10-2 mM, 0.1 mM and 1 mM) inhibited norepinephrine (NE), CaCl2 and KCl-induced vasoconstriction in a concentration dependent manner. The phasic contraction produced by NE was concentration dependently attenuated with CY (10^-2 mM, 0.1 mM and 1 mM) in calcium-free medium, similar to that caused by verapamil. The present findings suggest that CY relaxed thoracic aortic rings by blocking voltage-dependent Ca^2+ channels. The inhibition of intracellular Ca^2+ release may be one of the main vasorelaxant mechanisms of CY.