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
横纹肌溶解(rhabdomyolysis,RM)是一种多因素导致肌肉组织坏死后肌红蛋白(myoglobin,MB)、肌酸激酶(creatine kinase,CK)进入血液循环中的一种临床综合征。这些物质在体内的积累可导致严重的并发症,尤其是急性肾损伤(acute kidney injur...横纹肌溶解(rhabdomyolysis,RM)是一种多因素导致肌肉组织坏死后肌红蛋白(myoglobin,MB)、肌酸激酶(creatine kinase,CK)进入血液循环中的一种临床综合征。这些物质在体内的积累可导致严重的并发症,尤其是急性肾损伤(acute kidney injury,AKI)。血液吸附(hemoadsorption,HA)已被证实可以有效清除血液循环中的MB。2024年横纹肌溶解血液吸附工作组(consensus of the hemoadsorption in rhabdomyolysis task force,HRTF)制定了血液吸附清除肌红蛋白的国际共识。本文就该共识要点内容进行解读,供国内同行参考。展开更多
BACKGROUND:Heatstroke has become a common emergency event in hospitals.Procalcitonin(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heats...BACKGROUND:Heatstroke has become a common emergency event in hospitals.Procalcitonin(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heatstroke(EHS)remains unclear.METHODS:A retrospective cohort study enrolled patients with EHS from the intensive care unit(ICU).We collected RM biomarkers,inflammation markers,critical disease scores at admission,24 h,48 h,and discharge,and 90-day mortality.Correlation analysis,linear regression and curve fi tting were used to identify the relationship between PCT and RM.RESULTS:A total of 162 patients were recruited and divided into RM(n=56)and non-RM(n=106)groups.PCT was positively correlated with myoglobin(Mb),acute hepatic injury,disseminated intravascular coagulation(DIC),Sequential Organ Failure Assessment(SOFA)score,and Acute Physiology and Chronic Health Evaluation II(APACHE II)score,with correlation coefficients of 0.214,0.237,0.285,0.454,and 0.368,respectively(all P<0.05).Interestingly,the results of curve fi tting revealed a nonlinear relationship between PCT and RM,and a two-piecewise linear regression model showed that PCT was related to RM with an odds ratio of 1.3 and a cut-off of<4.6 ng/mL.Survival analysis revealed that RM was associated with higher mortality compared to non-RM cases(P=0.0093).CONCLUSION:High serum PCT concentrations are associated with RM after EHS in critically ill patients.Elevated PCT concentrations should be interpreted cautiously in patients with EHS in the ED.展开更多
信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)存在于细胞质、细胞核、线粒体及线粒体相关内质网膜中,是参与细胞增殖、分化、迁移和免疫调节等多种生理过程的信号转导蛋白。本文概述了STAT3的...信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)存在于细胞质、细胞核、线粒体及线粒体相关内质网膜中,是参与细胞增殖、分化、迁移和免疫调节等多种生理过程的信号转导蛋白。本文概述了STAT3的结构、类型及进入线粒体的途径;阐述了STAT3对细胞的稳态调节,包括介导内质网Ca^(2+)转运的细胞抗凋亡作用、维持线粒体功能的作用机制和对脂质合成与分解代谢的调控机制,进一步从对造血干细胞的调控作用、骨骼肌的调节、线粒体稳态调节和对脂肪合成与代谢的调控等方面探讨了STAT3调控肉色的机制,以期为改善肉色提供理论参考。展开更多
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.
文摘横纹肌溶解(rhabdomyolysis,RM)是一种多因素导致肌肉组织坏死后肌红蛋白(myoglobin,MB)、肌酸激酶(creatine kinase,CK)进入血液循环中的一种临床综合征。这些物质在体内的积累可导致严重的并发症,尤其是急性肾损伤(acute kidney injury,AKI)。血液吸附(hemoadsorption,HA)已被证实可以有效清除血液循环中的MB。2024年横纹肌溶解血液吸附工作组(consensus of the hemoadsorption in rhabdomyolysis task force,HRTF)制定了血液吸附清除肌红蛋白的国际共识。本文就该共识要点内容进行解读,供国内同行参考。
基金funded by the National Natural Science Foundation of China(82072143,81873943,82360903)Sanming Project of Medicine in Shenzhen(SZSM20162011)+3 种基金Shenzhen Science and Technology Innovation Commission(JCYJ20190806163603504)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project(20203357014,2023xgyj3357001,2023yjlcyj022)Guizhou Science and Technology Planning Project(Guizhou Science and Technology Cooperation Support[2021]General 413)and PhD Start-up Fund(GYZYYFY-BS-2023[09]).
文摘BACKGROUND:Heatstroke has become a common emergency event in hospitals.Procalcitonin(PCT)is used as a biomarker of infection in the emergency department(ED),but its role in rhabdomyolysis(RM)following exertional heatstroke(EHS)remains unclear.METHODS:A retrospective cohort study enrolled patients with EHS from the intensive care unit(ICU).We collected RM biomarkers,inflammation markers,critical disease scores at admission,24 h,48 h,and discharge,and 90-day mortality.Correlation analysis,linear regression and curve fi tting were used to identify the relationship between PCT and RM.RESULTS:A total of 162 patients were recruited and divided into RM(n=56)and non-RM(n=106)groups.PCT was positively correlated with myoglobin(Mb),acute hepatic injury,disseminated intravascular coagulation(DIC),Sequential Organ Failure Assessment(SOFA)score,and Acute Physiology and Chronic Health Evaluation II(APACHE II)score,with correlation coefficients of 0.214,0.237,0.285,0.454,and 0.368,respectively(all P<0.05).Interestingly,the results of curve fi tting revealed a nonlinear relationship between PCT and RM,and a two-piecewise linear regression model showed that PCT was related to RM with an odds ratio of 1.3 and a cut-off of<4.6 ng/mL.Survival analysis revealed that RM was associated with higher mortality compared to non-RM cases(P=0.0093).CONCLUSION:High serum PCT concentrations are associated with RM after EHS in critically ill patients.Elevated PCT concentrations should be interpreted cautiously in patients with EHS in the ED.
文摘信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)存在于细胞质、细胞核、线粒体及线粒体相关内质网膜中,是参与细胞增殖、分化、迁移和免疫调节等多种生理过程的信号转导蛋白。本文概述了STAT3的结构、类型及进入线粒体的途径;阐述了STAT3对细胞的稳态调节,包括介导内质网Ca^(2+)转运的细胞抗凋亡作用、维持线粒体功能的作用机制和对脂质合成与分解代谢的调控机制,进一步从对造血干细胞的调控作用、骨骼肌的调节、线粒体稳态调节和对脂肪合成与代谢的调控等方面探讨了STAT3调控肉色的机制,以期为改善肉色提供理论参考。
