Radiation-induced heart disease(RIHD),characterized by severe oxidative stress and immune dysregulation,is a serious condition affecting cancer patients undergoing thoracic radiation.Unfortunately,clinical interventio...Radiation-induced heart disease(RIHD),characterized by severe oxidative stress and immune dysregulation,is a serious condition affecting cancer patients undergoing thoracic radiation.Unfortunately,clinical interventions for RIHD are lacking.Selenium(Se)is a trace element with excellent antioxidant and immune-modulatory properties.However,its application in heart radioprotection remains challenging.Herein,we developed a novel bioactive Cordyceps militaris-based Se oral delivery system(Se@CM),which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation,compared to the radioprotectant Amifostine.Moreover,Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation,reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA.Additionally,Se@CM maintained immuno-homeostasis,as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation.Together,these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease.This research provides valuable insights into developing effective strategies for preventing and managing RIHD.展开更多
Over the past decades,the survival rates of patients with cancer have significantly increased owing to advancements in cancer treatment strategies.Radiotherapy has become an indispensable treatment modality for thorac...Over the past decades,the survival rates of patients with cancer have significantly increased owing to advancements in cancer treatment strategies.Radiotherapy has become an indispensable treatment modality for thoracic tumors.While it offers benefits in treating or even potentially curing cancer,thoracic radiotherapy exposes neighboring heart tissues to ionizing radiation,elevating the risk of radiation-induced heart disease(RIHD).Despite improvements in radiotherapy techniques that have reduced the incidence of RIHD,complete avoidance of heart radiation exposure remains a challenge.Cohort studies involving atomic bomb survivors and individuals with occupational radiation exposure,even at relatively low doses,have reported a significant increase in RIHD risks.The pathological mechanisms underlying RIHD have been extensively reviewed.At present,imaging techniques and traditional cardiac biomarkers are the primary methods to diagnose RIHD,with ongoing efforts to explore additional promising markers for predicting and monitoring RIHD.Moreover,traditional and novel therapeutic strategies are being actively explored to prevent or alleviate RIHD.Insights gained from therapeutic advancements in other organ systems or heart diseases caused by different factors can provide valuable ideas for RIHD management.This review discusses the recent advancements in the diagnosis and treatment of RIHD.展开更多
Radiofrequency catheter ablation （RFCA）,albeit an effective therapy for drug-refractory atrial fibrillation （AF）,can be associated with complications in 3.9-22.0% of cases, of which cerebrovascular embolization,ca...Radiofrequency catheter ablation （RFCA）,albeit an effective therapy for drug-refractory atrial fibrillation （AF）,can be associated with complications in 3.9-22.0% of cases, of which cerebrovascular embolization,cardiac tamponade,and pulmonary vein stenosis are more common,and atrial hematoma is more rare.Here,we presented a case describing an elderly woman diagnosed with an intramural left atrial hematoma after AF ablation.展开更多
Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed wi...Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency.However,whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.Methods：Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment.The contents of lactate dehydrogenase （LDH）,superoxide dismutase （SOD）,and malondialdehyde （MDA） in H9c2 cells were measured to investigate oxidative stress levels.The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry.The expression levels of proteins in the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （AKT）/P53 signaling pathway,inducible NOS （iNOS）,and endothelial NOS （eNOS） were examined using Western blotting.Results：X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner,whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition （control group vs.X-ray groups,respectively,P 〈 0.0 l）.X-ray radiation induced LDH release,apoptosis,and G0/G 1 peak accumulation,significantly increasing the level of MDA and the production of NO,and decreased the level of SOD （control group vs.X-ray groups,respectively,P 〈 0.05 or P 〈 0.01）.By contrast,BH4 treatment can significantly reverse these processes （BH4 treatment groups vs.X-ray groups,P 〈 0.05 or P 〈 0.01）.BH4 reversed the X-ray radiation-induced expression alterations ofapoptosis-related molecules,including B-cell lymphoma-2 （Bcl-2）,Bcl-2 associated X protein,and caspase-3,and molecules of the PI3K/Akt/P53 signaling pathway.BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.Conclusions：BH4 treatment can protect against X-ray-induced cardiomyocyte injury,possibly by recoupling eNOS rather than iNOS.BH4 treatment also decreased oxidative stress in radiated H9c2 cells.展开更多
Objective: To analyze the influencing factors for radiation-induced heart disease (RIHD) in a panel of cases with malignant thymic tumors treated by radiotherapy. Methods: 52 consecutive patients were treated by radi...Objective: To analyze the influencing factors for radiation-induced heart disease (RIHD) in a panel of cases with malignant thymic tumors treated by radiotherapy. Methods: 52 consecutive patients were treated by radiotherapy for malignant thymic tumor (14 at Masaoka stage II, 23 at stage III and 15 at stage IV). Treatment included radical (in 20), postoperative (in 14), preoperative (in 2) and palliative (in 16) radiotherapy. The conventional two-dimension (2D) radiation therapy was performed in forty-seven patients and three-dimension (3D) conformal radiation therapy has been used in 5 patients since October 2000. The total tumor dose ranged from 10 Gy to 84.5 Gy (median of 55 Gy). Chemotherapy was given in twenty-five patients before or after radiotherapy. The results of following-up could be obtained from the database and updated where appropriated. The dose volume histogram (DVH) of heart in radiotherapy for all patients was analyzed for the effective volume dose of heart. Result: The median following-up was 14 months (ranged from 0.6 to 111.3 months) in the study. RIHD was observed in seven patients. Cardiac toxicity of these seven patients were evaluated as SOMA grade 1-3. The median two-third effective volume dose of heart was 47.2 Gy (ranged from 8.3 Gy to 70.1 Gy) for conventional 2D radiotherapy, which correlated with thymic tumor dose (P<0.0001). The median two-third effective volume dose of heart was 35.3 Gy (ranged from 13 Gy to 38.7 Gy) for 3D conformal radiotherapy. The effective volume doses of heart were decreased by using 3D conformal radiotherapy (P=0.048). A significant association between cardiac toxicity and effective volume dose of heart was found in this study (P<0.0001). Cardiac toxicity accounted for 10.4% and 4.1% of patients receiving and not receiving adjuvant chemotherapy, respectively, and occurred earlier in radiochemotherapy group (P=0.0528). Multivariate analysis suggested that cardiac toxicity was significantly influenced by the effective volume dose of heart and chemotherapy. Conclusion: the results indicate that decreasing the effective volume dose of heart and carefully using chemotherapy drugs that have significant cardiotoxicity may reduce the probability of radiation-induced heart disease.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars (82225025)National Natural Science Foundation of China (21877049,32171296,32101044)+1 种基金Guangdong Natural Science Foundation (2020B1515120043)K.C.Wong Education Foundation and China Postdoctoral Science Foundation (2022M711341).
文摘Radiation-induced heart disease(RIHD),characterized by severe oxidative stress and immune dysregulation,is a serious condition affecting cancer patients undergoing thoracic radiation.Unfortunately,clinical interventions for RIHD are lacking.Selenium(Se)is a trace element with excellent antioxidant and immune-modulatory properties.However,its application in heart radioprotection remains challenging.Herein,we developed a novel bioactive Cordyceps militaris-based Se oral delivery system(Se@CM),which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation,compared to the radioprotectant Amifostine.Moreover,Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation,reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA.Additionally,Se@CM maintained immuno-homeostasis,as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation.Together,these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease.This research provides valuable insights into developing effective strategies for preventing and managing RIHD.
基金the National Natural Science Foundation of China(No.82270360)the Natural Science Foundation of Jiangsu Province(No.BK20231183)+1 种基金the Project of Science and Technology Department of Jiangxi Province(No.20204BCJ23018)the Young Science and Technology Innovation Team of Xuzhou Medical University,China.
文摘Over the past decades,the survival rates of patients with cancer have significantly increased owing to advancements in cancer treatment strategies.Radiotherapy has become an indispensable treatment modality for thoracic tumors.While it offers benefits in treating or even potentially curing cancer,thoracic radiotherapy exposes neighboring heart tissues to ionizing radiation,elevating the risk of radiation-induced heart disease(RIHD).Despite improvements in radiotherapy techniques that have reduced the incidence of RIHD,complete avoidance of heart radiation exposure remains a challenge.Cohort studies involving atomic bomb survivors and individuals with occupational radiation exposure,even at relatively low doses,have reported a significant increase in RIHD risks.The pathological mechanisms underlying RIHD have been extensively reviewed.At present,imaging techniques and traditional cardiac biomarkers are the primary methods to diagnose RIHD,with ongoing efforts to explore additional promising markers for predicting and monitoring RIHD.Moreover,traditional and novel therapeutic strategies are being actively explored to prevent or alleviate RIHD.Insights gained from therapeutic advancements in other organ systems or heart diseases caused by different factors can provide valuable ideas for RIHD management.This review discusses the recent advancements in the diagnosis and treatment of RIHD.
文摘Radiofrequency catheter ablation （RFCA）,albeit an effective therapy for drug-refractory atrial fibrillation （AF）,can be associated with complications in 3.9-22.0% of cases, of which cerebrovascular embolization,cardiac tamponade,and pulmonary vein stenosis are more common,and atrial hematoma is more rare.Here,we presented a case describing an elderly woman diagnosed with an intramural left atrial hematoma after AF ablation.
基金This work was supported by the National Natural Science Foundation of China （No. 81270332）, and Gansu Province Health Industry Scientific Research Plan （No. GSWSKY-2014-33）.
文摘Background：Tetrahydrobiopterin （BH4） is an essential cofactor of nitric oxide synthases （NOSs） for the synthesis of nitric oxide （NO）.BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency.However,whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown.Methods：Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment.The contents of lactate dehydrogenase （LDH）,superoxide dismutase （SOD）,and malondialdehyde （MDA） in H9c2 cells were measured to investigate oxidative stress levels.The cell cycle undergoing radiation with or without BH4 treatment was detected using flow cytometry.The expression levels of proteins in the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （AKT）/P53 signaling pathway,inducible NOS （iNOS）,and endothelial NOS （eNOS） were examined using Western blotting.Results：X-ray radiation significantly inhibited the growth of H9c2 cells in a dose-dependent manner,whereas BH4 treatment significantly reduced the X-ray radiation-induced growth inhibition （control group vs.X-ray groups,respectively,P 〈 0.0 l）.X-ray radiation induced LDH release,apoptosis,and G0/G 1 peak accumulation,significantly increasing the level of MDA and the production of NO,and decreased the level of SOD （control group vs.X-ray groups,respectively,P 〈 0.05 or P 〈 0.01）.By contrast,BH4 treatment can significantly reverse these processes （BH4 treatment groups vs.X-ray groups,P 〈 0.05 or P 〈 0.01）.BH4 reversed the X-ray radiation-induced expression alterations ofapoptosis-related molecules,including B-cell lymphoma-2 （Bcl-2）,Bcl-2 associated X protein,and caspase-3,and molecules of the PI3K/Akt/P53 signaling pathway.BH4 enhanced the production of NO in 2 Gy and 4 Gy radiated groups by upregulating eNOS protein expression and downregulating iNOS protein expression.Conclusions：BH4 treatment can protect against X-ray-induced cardiomyocyte injury,possibly by recoupling eNOS rather than iNOS.BH4 treatment also decreased oxidative stress in radiated H9c2 cells.
文摘Objective: To analyze the influencing factors for radiation-induced heart disease (RIHD) in a panel of cases with malignant thymic tumors treated by radiotherapy. Methods: 52 consecutive patients were treated by radiotherapy for malignant thymic tumor (14 at Masaoka stage II, 23 at stage III and 15 at stage IV). Treatment included radical (in 20), postoperative (in 14), preoperative (in 2) and palliative (in 16) radiotherapy. The conventional two-dimension (2D) radiation therapy was performed in forty-seven patients and three-dimension (3D) conformal radiation therapy has been used in 5 patients since October 2000. The total tumor dose ranged from 10 Gy to 84.5 Gy (median of 55 Gy). Chemotherapy was given in twenty-five patients before or after radiotherapy. The results of following-up could be obtained from the database and updated where appropriated. The dose volume histogram (DVH) of heart in radiotherapy for all patients was analyzed for the effective volume dose of heart. Result: The median following-up was 14 months (ranged from 0.6 to 111.3 months) in the study. RIHD was observed in seven patients. Cardiac toxicity of these seven patients were evaluated as SOMA grade 1-3. The median two-third effective volume dose of heart was 47.2 Gy (ranged from 8.3 Gy to 70.1 Gy) for conventional 2D radiotherapy, which correlated with thymic tumor dose (P<0.0001). The median two-third effective volume dose of heart was 35.3 Gy (ranged from 13 Gy to 38.7 Gy) for 3D conformal radiotherapy. The effective volume doses of heart were decreased by using 3D conformal radiotherapy (P=0.048). A significant association between cardiac toxicity and effective volume dose of heart was found in this study (P<0.0001). Cardiac toxicity accounted for 10.4% and 4.1% of patients receiving and not receiving adjuvant chemotherapy, respectively, and occurred earlier in radiochemotherapy group (P=0.0528). Multivariate analysis suggested that cardiac toxicity was significantly influenced by the effective volume dose of heart and chemotherapy. Conclusion: the results indicate that decreasing the effective volume dose of heart and carefully using chemotherapy drugs that have significant cardiotoxicity may reduce the probability of radiation-induced heart disease.
