The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and auto...The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.展开更多
Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our...Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our study,we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region.Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages,we conjugated a peptide sequence,cations-cysteine-alanine-glutamine-lysine(CAQK),with the mitochondria,optimizing its targeting affinity for the injury site.Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris,curtailed lipid buildup,ameliorated mitochondrial dysfunction,and attenuated pro-inflammatory profiles in macrophages,both in vitro and in vivo.The intravenously delivered mitochondrial compounds targeted the SCI epicenter,with macrophages being the primary recipients.Critically,they promoted tissue regeneration and bolstered functional recovery in SCI mice.This study heralds a transformative approach to mitochondrial transplantation in SCI,spotlighting the modulation of macrophage activity,phagocytosis,and phenotype.展开更多
OBJECTIVE:To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome(CFS)and explore the effects on gut microbiota and metabolic profiles.METHODS:Forty-eight male Sprague-Dawley rats were rand...OBJECTIVE:To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome(CFS)and explore the effects on gut microbiota and metabolic profiles.METHODS:Forty-eight male Sprague-Dawley rats were randomly assigned to control group(Con),CFS model group(Mod,established by multiple chronic stress for 35 d),MoxA group(CFS model with moxibustion Shenque(CV8)and Guanyuan(CV4),10 min/d,28 d)and MoxB group(CFS model with moxibustion Zusanli(ST36),10 min/d,28 d).Open-field test(OFT)and Morris-water-maze test(MWMT)were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer(LC-MS)based fecal metabolomics were executed,as well as Spearman correlation analysis,was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.RESULTS:The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT.Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition,including increases in pro-inflammatory species(such as Proteobacteria)and decreases in anti-inflammatory species(such as Bacteroides,Lactobacillus,Ruminococcus,and Prevotella).Moxibustion partially normalized these changes in the gut microbiota.Furthermore,CFS was associated with metabolic disorders,which were effectively ameliorated by moxibustion.This was demonstrated by the normalization of 33 microbiota-related metabolites,including mannose(P=0.001),aspartic acid(P=0.009),alanine(P=0.007),serine(P=0.000),threonine(P=0.027),methionine(P=0.023),5-hydroxytryptamine(P=0.008),alpha-linolenic acid(P=0.003),eicosapentaenoic acid(P=0.006),hypoxanthine(P=0.000),vitamin B6(P=0.000),cholic acid(P=0.013),and taurocholate(P=0.002).Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels,with a notable negative relations展开更多
意义未明的单克隆免疫球蛋白血症(monoclonalgammopathy of undetermined significance,MGUS)被认为是一种癌前病变,在欧美地区50岁以上人群的发病率为3.2%,其诊断需要符合血清M蛋白<30g/L、骨髓单克隆浆细胞<10%、不存在浆细胞...意义未明的单克隆免疫球蛋白血症(monoclonalgammopathy of undetermined significance,MGUS)被认为是一种癌前病变,在欧美地区50岁以上人群的发病率为3.2%,其诊断需要符合血清M蛋白<30g/L、骨髓单克隆浆细胞<10%、不存在浆细胞增殖相关的终末器官损害^([1-2])。当MGUS患者合并肾损伤时(除外高血压、糖尿病等其他原因),称为有肾脏意义的单克隆免疫球蛋白血症(monoclonal gam-mopathy of renal significance,MGRS)^([3])。展开更多
基金This study was financially supported by The National Key Research and Development Program of China(grant number 2020YFC2008205)The National Natural Science Foundation of China(grant numbers 82171058,81974134,and 81974137)+1 种基金The Key R&D Plan of Hunan Province of China(No.2020SK2076)Natural Science Foundation of Hunan Province(No.2019JJ40507 and 2023JJ30956).
文摘The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.
基金supported by the Key Program of the National Natural Science Foundation of China(No.82030071)the National Natural Science Foundation of China(No.82202722,No.81874004)+3 种基金the Science and Technology Major Project of Changsha(No.kh2103008)the Science Foundation of Xiangya Hospital for Young Scholar(Grant No.2021q18)the Natural Science Foundation of Changsha city(Grant No.kq2202378)Graduate students of Central South University independently explore innovative projects(2022ZZTS094).
文摘Mitochondria are crucial in sustaining and orchestrating cellular functions.Capitalizing on this,we explored mitochondrial transplantation as an innovative therapeutic strategy for acute spinal cord injury(SCI).In our study,we developed an engineered mitochondrial compound tailored to target macrophages within the SCI region.Sourced from IL-10-induced Mertkhi bone marrow-derived macrophages,we conjugated a peptide sequence,cations-cysteine-alanine-glutamine-lysine(CAQK),with the mitochondria,optimizing its targeting affinity for the injury site.Our data demonstrated that these compounds significantly enhanced macrophage phagocytosis of myelin debris,curtailed lipid buildup,ameliorated mitochondrial dysfunction,and attenuated pro-inflammatory profiles in macrophages,both in vitro and in vivo.The intravenously delivered mitochondrial compounds targeted the SCI epicenter,with macrophages being the primary recipients.Critically,they promoted tissue regeneration and bolstered functional recovery in SCI mice.This study heralds a transformative approach to mitochondrial transplantation in SCI,spotlighting the modulation of macrophage activity,phagocytosis,and phenotype.
基金National Natural Science Foundation of China:Based on TGF-β/Smad Signaling Pathway to Studying the Role and Mechanism of NF-κB in the Treatment of Chronic Fatigue Syndrome with Electroacupuncture (No.81704170)National Natural Science Foundation of China:Mechanism Study on Electroacupuncture Regulating MDM2 Ubiquitination PSD-95 Level and Remodeling Synaptic Structure of Hippocampal Neurons to Improve Cognitive Dysfunction in CFS (No.81873378)+7 种基金the Joint Guiding Project of Natural Science Foundation of Heilongjiang Province:Study on the Mechanism of Electroacupuncture Adjusting Gut Microbiota to Improve Oxidative Inflammatory Response in the Treatment of Chronic Fatigue Syndrome (No.LH2020H092)The Program of Heilongjiang Postdoctoral Initiation Fund:Experimental Study on Electroacupuncture Improving Protein Expression Differences and Target Effects in Hippocampus and Hypothalamus of Rats with Chronic Fatigue Syndrome (No.LBH-Q18117)Heilongjiang Administration of Traditional Chinese Medicine:Study on the Effect and Mechanism of Moxibustion on Gut Microbiota in Rats with Chronic Fatigue Syndrome (No.ZHY2020-79)The Mechanism of TGF-β/Smad Mediated NF-κB Inflammatory Pathway in the Treatment of Chronic Fatigue Syndrome by Electroacupuncture (No.ZHY16-003)The Mechanism of Electroacupuncture Improving Hippocampal Synaptic Plasticity in CFS Cognitive Dysfunction Rats (ZHY2022-136)Zhejiang Chinese Medical University Scientific Research:Study on the Mechanism of Moxibustion Regulating the Gut Microbiota of Chronic Fatigue Syndrome Targeting the 5-HT Signal System (No.2021RCZXZK02)Basic Public Welfare Project of the Third Affiliated Hospital of Zhejiang Chinese Medical University:Study on the Mechanism of Moxibustion Repairing the Barrier Function-Inflammatory Response of Chronic Fatigue Syndrome by the Gut-Brain Axis (No.ZS21ZA08)Scientific Research Foundation of Heilongjiang University of Chinese Medicine:Based on Gut Microbiota and Metabolism to Study the Mechanism in the Treatment of Chronic Fatigue Syndrome
文摘OBJECTIVE:To observe the efficacy of moxibustion in the treatment of chronic fatigue syndrome(CFS)and explore the effects on gut microbiota and metabolic profiles.METHODS:Forty-eight male Sprague-Dawley rats were randomly assigned to control group(Con),CFS model group(Mod,established by multiple chronic stress for 35 d),MoxA group(CFS model with moxibustion Shenque(CV8)and Guanyuan(CV4),10 min/d,28 d)and MoxB group(CFS model with moxibustion Zusanli(ST36),10 min/d,28 d).Open-field test(OFT)and Morris-water-maze test(MWMT)were determined for assessment the CFS model and the therapeutic effects of moxibustion.16S rRNA gene sequencing analysis based gut microbiota integrated untargeted liquid chromatograph-mass spectrometer(LC-MS)based fecal metabolomics were executed,as well as Spearman correlation analysis,was utilized to uncover the functional relevance between the potential metabolites and gut microbiota.RESULTS:The results of our behavioral tests showed that moxibustion improved the performance of CFS rats in the OFT and the MWMT.Microbiome profiling analysis revealed that the gut microbiomes of CFS rats were less diverse with altered composition,including increases in pro-inflammatory species(such as Proteobacteria)and decreases in anti-inflammatory species(such as Bacteroides,Lactobacillus,Ruminococcus,and Prevotella).Moxibustion partially normalized these changes in the gut microbiota.Furthermore,CFS was associated with metabolic disorders,which were effectively ameliorated by moxibustion.This was demonstrated by the normalization of 33 microbiota-related metabolites,including mannose(P=0.001),aspartic acid(P=0.009),alanine(P=0.007),serine(P=0.000),threonine(P=0.027),methionine(P=0.023),5-hydroxytryptamine(P=0.008),alpha-linolenic acid(P=0.003),eicosapentaenoic acid(P=0.006),hypoxanthine(P=0.000),vitamin B6(P=0.000),cholic acid(P=0.013),and taurocholate(P=0.002).Correlation analysis showed a significant association between the perturbed fecal microbiota and metabolite levels,with a notable negative relations
文摘意义未明的单克隆免疫球蛋白血症(monoclonalgammopathy of undetermined significance,MGUS)被认为是一种癌前病变,在欧美地区50岁以上人群的发病率为3.2%,其诊断需要符合血清M蛋白<30g/L、骨髓单克隆浆细胞<10%、不存在浆细胞增殖相关的终末器官损害^([1-2])。当MGUS患者合并肾损伤时(除外高血压、糖尿病等其他原因),称为有肾脏意义的单克隆免疫球蛋白血症(monoclonal gam-mopathy of renal significance,MGRS)^([3])。
