Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivati...Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.展开更多
Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is u...Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is unpredictable.Minor symptoms may resolve spontaneously or require conservative treatment.On the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment measures.Over the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is conflicting.Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical practice.This article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.展开更多
After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on ...After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.展开更多
Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor recurrence.To overcome these challenges,hydrogels have been employe...Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor recurrence.To overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic agents.This review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer treatment.Firstly,we introduce the classification and properties of hydrogels.Next,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and brachytherapy.We also discuss hydrogels used in combination therapy involving RT and immunotherapy.Lastly,we highlight the challenges that hydrogels face in RT.By surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.展开更多
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain ...BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.展开更多
After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of ox...After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.展开更多
After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow ...After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.展开更多
Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivo...Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.展开更多
Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve ...Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.展开更多
基金supported by the National Natural Science Foundation of China,No.82002400(to GJZ)Scientific Research Project of Hu nan Health Committee,No.20201911and No.20200469(both to ZJX)+2 种基金Scientific Research Project of Hunan Health Committee,No.20211411761(to HMW)the Natural Science Foundation of Hunan Province,No.2020JJ5512(to GJZ)a grant from Clinical Medical Technology Innovation Guidance Project in Hunan Province,No.2020SK51822(to ZJX)。
文摘Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.
文摘Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is unpredictable.Minor symptoms may resolve spontaneously or require conservative treatment.On the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment measures.Over the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is conflicting.Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical practice.This article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.
基金supported by the in-house Laboratory Independent Research (ILIR) program of the U.S. Army
文摘After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.
基金supported by Funds of Sichuan Province for Distinguished Young Scholar(No.2021JDJQ0037)Key Research and Development Program of Sichuan Province(No.2023YFS0153)1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYYC08002).
文摘Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor recurrence.To overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic agents.This review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer treatment.Firstly,we introduce the classification and properties of hydrogels.Next,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and brachytherapy.We also discuss hydrogels used in combination therapy involving RT and immunotherapy.Lastly,we highlight the challenges that hydrogels face in RT.By surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
基金a Project for Nuclear Military Personal Health Assessment and Radiation Damage Treat-ment, No. 616010305
文摘BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.
文摘After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.
文摘After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.
文摘Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.
基金supported by Key Project of China Rehabilitation Research Center,Nos.2022ZX-05,2018ZX-08(both to JB)。
文摘Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.
