Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immu...Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair.However,accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome,especially small extracellular vesicles(sEVs).sEVs are signaling vehicles in intercellular communication in normal or pathological conditions.sEVs contain natural contents,such as proteins,mRNA,and microRNAs,and transfer these functional contents to adjacent cells or distant cells through the circulatory system.MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases.The properties of MSC-sEVs include stability in circulation,good biocompatibility,and low toxicity and immunogenicity.Moreover,emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease.This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.展开更多
BACKGROUND:Earthquakes,floods,droughts,storms,mudslides,landslides,and forest wild fires are serious threats to human lives and properties.The present study aimed to study the environmental characteristics and pathoge...BACKGROUND:Earthquakes,floods,droughts,storms,mudslides,landslides,and forest wild fires are serious threats to human lives and properties.The present study aimed to study the environmental characteristics and pathogenic traits,recapitulate experiences,and augment applications of medical reliefs in tropical regions.METHODS:Analysis was made on work and projects of emergency medical rescue,based on information and data collected from 3 emergency medical rescue missions of China International Search and Rescue Team to overseas earthquakes and tsunamis aftermaths in tropical disaster regions — Indonesia-Aceh,Indonesia-Yogyakarta,and Haiti-Port au Prince.RESULTS:Shock,infection and heat stroke were frequently encountered in addition to outbreaks of infectious diseases,skin diseases,and diarrhea during post-disaster emergency medical rescue in tropical regions.CONCLUSIONS:High temperature,high humidity,and proliferation of microorganisms and parasites are the characteristics of tropical climate that impose strict requirements on the preparation of rescue work including selective team members suitable for a particular rescue mission and the provisioning of medical equipment and life support materials.The overseas rescue mission itself needs a scientific,efficient,simple workflow for providing efficient emergency medical assistance.Since shock and infection are major tasks in post-disaster treatment of severely injured victims in tropical regions,the prevention and diagnosis of hyperthermia,insect-borne infectious diseases,tropic skin diseases,infectious diarrhea,and pest harms of disaster victims and rescue team staff should be emphasized during the rescue operations.展开更多
Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I...Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I(RIG-I)has been reported to exert anti-viral effects function in the innate immune response.However,it is not clear whether RIG-I plays a role in CS-AKI.The present research was carried out to explore the role of RIG-I in CS-AKI.Methods:Sprague-Dawley rats were randomly divided into two groups:the sham and CS groups(n=12).After administration of anesthesia,the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions.The rats in both groups were denied access to food and water.Rats were sacrificed at 12 h or 36 h after pressure was relieved.The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination.In addition,RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI.Furthermore,NRK-52 E cells were treated with 200μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level.The cells and cell supernatant samples were collected at 6 h or 24 h.Small interfering RNAs(siRNA)was used to knock down RIG-I expression.The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative real-time PCR(qPCR),Western blotting analysis,and immunohistochemistry(IHC)staining.Tumor necrosis factor-α(TNF-α)was d etected by ELISA.Co-immunoprecipitation(Co-IP)assays were used to detect the interaction between RIG-I and myoglobin.Results:RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway.qPCR,Western blotting,and IHC assays showed that RIG-I,nuclear factor kappa-B(NF-κB)P65,p-P65,and the a poptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group(P<0.05).However,the levels of interferon regulatory factor 3(IRF3),p-IRF3 and the antiviral factor interferon-beta(IFN-β)showed no significant c hanges between the sham and CS groups.Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group.Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.C onclusions:RIG-I is a novel damage-associated molecular patterns(DAMPs)sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI.In the development of CS-AKI,specific intervention in the RIG-I p athway might be a potential therapeutic strategy for CS-AKI.展开更多
Rhabdomyolysis(RM)is a multifactorial clinical syndrome characterized by the disintegration and necrosis of muscle tissue,leading to the release of cellular contents into the circulation.One of the most severe complic...Rhabdomyolysis(RM)is a multifactorial clinical syndrome characterized by the disintegration and necrosis of muscle tissue,leading to the release of cellular contents into the circulation.One of the most severe complications of RM is acute kidney injury,with a mortality rate of 20%e50%.Early and timely diagnosis is the key to improving the prognosis of patients with RM.The etiology of RM is complex and associated with various trauma drugs,medications,and hereditary diseases,and the clinical symptoms are nonspecific.Therefore,its diagnosis highly relies on the doctor's experience and the level of medical equipment.However,RM often occurs in situations with limited medical resources,such as natural disasters,battlefields,and large-scale traffic accidents.In these scenarios,the varying levels of expertise among rescue personnel can lead to delays in diagnosis and treatment,thereby increasing the risk of mortality.This article provides a comprehensive review of the etiology,pathogenesis,complications,diagnostic,and treatment methods of RM.It also aims to offer new perspectives on the diagnosis and prognosis of RM by integrating machine learning and artificial intelligence.It is believed that this article can help pre-hospital rescuers and in-hospital doctors have a comprehensive understanding of RM to improve the patients'outcomes and overcome the challenges.展开更多
基金Supported by National Natural Science Foundation of China,No.81971878Opening Project of Military Logistics,No.BLB19J006and Tianjin University Independent Innovation Fund,No.2020XRG-0027,No.2020XYF-0041,and No.2020XZY-0086.
文摘Mesenchymal stem cells(MSCs)are self-renewing,multipotent cells that could differentiate into multiple tissues.MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair.However,accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome,especially small extracellular vesicles(sEVs).sEVs are signaling vehicles in intercellular communication in normal or pathological conditions.sEVs contain natural contents,such as proteins,mRNA,and microRNAs,and transfer these functional contents to adjacent cells or distant cells through the circulatory system.MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases.The properties of MSC-sEVs include stability in circulation,good biocompatibility,and low toxicity and immunogenicity.Moreover,emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease.This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.
基金supported by a grant from Capital Medical Development Scientific Research Fund(2009-1029)
文摘BACKGROUND:Earthquakes,floods,droughts,storms,mudslides,landslides,and forest wild fires are serious threats to human lives and properties.The present study aimed to study the environmental characteristics and pathogenic traits,recapitulate experiences,and augment applications of medical reliefs in tropical regions.METHODS:Analysis was made on work and projects of emergency medical rescue,based on information and data collected from 3 emergency medical rescue missions of China International Search and Rescue Team to overseas earthquakes and tsunamis aftermaths in tropical disaster regions — Indonesia-Aceh,Indonesia-Yogyakarta,and Haiti-Port au Prince.RESULTS:Shock,infection and heat stroke were frequently encountered in addition to outbreaks of infectious diseases,skin diseases,and diarrhea during post-disaster emergency medical rescue in tropical regions.CONCLUSIONS:High temperature,high humidity,and proliferation of microorganisms and parasites are the characteristics of tropical climate that impose strict requirements on the preparation of rescue work including selective team members suitable for a particular rescue mission and the provisioning of medical equipment and life support materials.The overseas rescue mission itself needs a scientific,efficient,simple workflow for providing efficient emergency medical assistance.Since shock and infection are major tasks in post-disaster treatment of severely injured victims in tropical regions,the prevention and diagnosis of hyperthermia,insect-borne infectious diseases,tropic skin diseases,infectious diarrhea,and pest harms of disaster victims and rescue team staff should be emphasized during the rescue operations.
基金supported by the Tianjin UniversityaDouble First Classoconstruction talent start-up fund to Dr.Yan-Hua Gong,the grants awarded to Shi-Ke Hou by Science and Technology Commission of the CMC(c12019048)Ning Li by Open Fund of State Key Laboratory of Medicinal Chemical Biology(Nankai University)(2020010)。
文摘Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I(RIG-I)has been reported to exert anti-viral effects function in the innate immune response.However,it is not clear whether RIG-I plays a role in CS-AKI.The present research was carried out to explore the role of RIG-I in CS-AKI.Methods:Sprague-Dawley rats were randomly divided into two groups:the sham and CS groups(n=12).After administration of anesthesia,the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions.The rats in both groups were denied access to food and water.Rats were sacrificed at 12 h or 36 h after pressure was relieved.The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination.In addition,RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI.Furthermore,NRK-52 E cells were treated with 200μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level.The cells and cell supernatant samples were collected at 6 h or 24 h.Small interfering RNAs(siRNA)was used to knock down RIG-I expression.The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative real-time PCR(qPCR),Western blotting analysis,and immunohistochemistry(IHC)staining.Tumor necrosis factor-α(TNF-α)was d etected by ELISA.Co-immunoprecipitation(Co-IP)assays were used to detect the interaction between RIG-I and myoglobin.Results:RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway.qPCR,Western blotting,and IHC assays showed that RIG-I,nuclear factor kappa-B(NF-κB)P65,p-P65,and the a poptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group(P<0.05).However,the levels of interferon regulatory factor 3(IRF3),p-IRF3 and the antiviral factor interferon-beta(IFN-β)showed no significant c hanges between the sham and CS groups.Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group.Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.C onclusions:RIG-I is a novel damage-associated molecular patterns(DAMPs)sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI.In the development of CS-AKI,specific intervention in the RIG-I p athway might be a potential therapeutic strategy for CS-AKI.
基金financially supported by the National Key R&D Program of China(No.2021YFC3002200)the Tianjin Research Innovation Project for Postgraduate Students(No.2021YJSB190).
文摘Rhabdomyolysis(RM)is a multifactorial clinical syndrome characterized by the disintegration and necrosis of muscle tissue,leading to the release of cellular contents into the circulation.One of the most severe complications of RM is acute kidney injury,with a mortality rate of 20%e50%.Early and timely diagnosis is the key to improving the prognosis of patients with RM.The etiology of RM is complex and associated with various trauma drugs,medications,and hereditary diseases,and the clinical symptoms are nonspecific.Therefore,its diagnosis highly relies on the doctor's experience and the level of medical equipment.However,RM often occurs in situations with limited medical resources,such as natural disasters,battlefields,and large-scale traffic accidents.In these scenarios,the varying levels of expertise among rescue personnel can lead to delays in diagnosis and treatment,thereby increasing the risk of mortality.This article provides a comprehensive review of the etiology,pathogenesis,complications,diagnostic,and treatment methods of RM.It also aims to offer new perspectives on the diagnosis and prognosis of RM by integrating machine learning and artificial intelligence.It is believed that this article can help pre-hospital rescuers and in-hospital doctors have a comprehensive understanding of RM to improve the patients'outcomes and overcome the challenges.
