Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly ...Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillar...Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the brain.The overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of AD.Apparently,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD.Recently,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ligands.Here,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD mice.The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of Cory-B.Notably,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.展开更多
Alzheimer's disease(AD),characterized by the accumulation of protein aggregates including phosphorylated Tau aggregates,is the most common neurodegenerative disorder with limited therapeutic agents.Autophagy plays...Alzheimer's disease(AD),characterized by the accumulation of protein aggregates including phosphorylated Tau aggregates,is the most common neurodegenerative disorder with limited therapeutic agents.Autophagy plays a critical role in the degradation of phosphorylated Tau aggregates,and transcription factor EB(TFEB)is a master regulator of autophagy and lysosomal biogenesis.Thus,small-molecule autophagy enhancers targeting TFEB hold promise for AD therapy.Here,we found that celastrol,an active ingredient isolated from the root extracts of Tripterygium wilfordii(Lei Gong Teng in Chinese)enhanced TFEB-mediated autophagy and lysosomal biogenesis in vitro and in mouse brains.Importantly,celastrol reduced phosphorylated Tau aggregates and attenuated memory dysfunction and cognitive deficits in P301S Tau and 3xTg mice,two commonly used AD animal models.Mechanistical studies suggest that TFEB-mediated autophagy-lysosomal pathway is responsible for phosphorylated Tau degradation in response to celastrol.Overall,our findings indicate that Celastrol is a novel TFEB activator that promotes the degradation of phosphorylated Tau aggregates and improves memory in AD animal models.Therefore,Celastrol shows potential as a novel agent for the treatment and/or prevention of AD and other tauopathies.展开更多
文摘Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
基金the grants of Health and Medical Research Fund HMRF/17182541(ML)Health and Medical Research Fund HMRF/17182551(AlI)+10 种基金Matching Proof-of-Concept Fund(MPCF)HKBU-MPCF-003-2022-23(AI)Health and Medical Research Fund HMRF/09203776(ML)Research Grants Council of Hong Kong,General Research Fund GRF/2100618(ML)Research Grants Council of Hong Kong,General Research Fund GRF/12101022(ML)Research Grants Council of Hong Kong,Collaborative Research Fund C2011-21GF(ML)Hong Kong Baptist University Grant HKBU/RC-IRCs/17-18/03(ML)Hong Kong Baptist University Grant IRCMS/19-20/H02(ML,Al)U.S.National Institute of Health,NCI R00 CA226353-01A1(HJC)U.S.National Institute of Health,NCI K99 CA226353-01A1(HJC)Cancer Research Foundation Young Investigator Award(HJC)LCRF pilot grant(HJC).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques,hyperphosphorylated tau protein,and neurofibrillary tangles in the brain.The overexpression of amyloid-βprecursor protein(APP)in an AD brain results in the binding of APP intracellular domain(AICD)to Fe65 protein via the C-terminal Fe65-PTB2 interaction,which then triggers the secretion of amyloid-βand the consequent pathogenesis of AD.Apparently,targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD.Recently,exosome,a type of extracellular vesicle with diameter around 30–200 nm,has gained much attention as a potential delivery tool for brain diseases,including AD,due to their ability to cross the blood–brain barrier,their efficient uptake by autologous cells,and their ability to be surface-modified with target-specific receptor ligands.Here,the engineering of hippocampus neuron cell-derived exosomes to overexpress Fe65,enabled the development of a novel exosome-based targeted drug delivery system,which carried Corynoxine-B(Cory-B,an autophagy inducer)to the APP overexpressed-neuron cells in the brain of AD mice.The Fe65-engineered HT22 hippocampus neuron cell-derived exosomes(Fe65-EXO)loaded with Cory-B(Fe65-EXO-Cory-B)hijacked the signaling and blocked the natural interaction between Fe65 and APP,enabling APP-targeted delivery of Cory-B.Notably,Fe65-EXO-Cory-B induced autophagy in APP-expressing neuronal cells,leading to amelioration of the cognitive decline and pathogenesis in AD mice,demonstrating the potential of Fe65-EXO-Cory-B as an effective therapeutic intervention for AD.
基金This study was supported by the research fund from Hong Kong Baptist University(HKBU/RC-IRCs/17-18/03,China)Hong Kong General Research Fund(GRF/HKBU12101417 and GRF/HKBU12100618,China)+2 种基金the National Natural Science Foundation of China(81703487 and 81773926)Shenzhen Science and Technology Innovation Commission(JCYJ20180302174028790,JCYJ20180507184656626,and JCYJ20210324114014039,China)the Hong Kong Health and Medical Research Fund(HMRF17182541 and HMRF17182551,China).
文摘Alzheimer's disease(AD),characterized by the accumulation of protein aggregates including phosphorylated Tau aggregates,is the most common neurodegenerative disorder with limited therapeutic agents.Autophagy plays a critical role in the degradation of phosphorylated Tau aggregates,and transcription factor EB(TFEB)is a master regulator of autophagy and lysosomal biogenesis.Thus,small-molecule autophagy enhancers targeting TFEB hold promise for AD therapy.Here,we found that celastrol,an active ingredient isolated from the root extracts of Tripterygium wilfordii(Lei Gong Teng in Chinese)enhanced TFEB-mediated autophagy and lysosomal biogenesis in vitro and in mouse brains.Importantly,celastrol reduced phosphorylated Tau aggregates and attenuated memory dysfunction and cognitive deficits in P301S Tau and 3xTg mice,two commonly used AD animal models.Mechanistical studies suggest that TFEB-mediated autophagy-lysosomal pathway is responsible for phosphorylated Tau degradation in response to celastrol.Overall,our findings indicate that Celastrol is a novel TFEB activator that promotes the degradation of phosphorylated Tau aggregates and improves memory in AD animal models.Therefore,Celastrol shows potential as a novel agent for the treatment and/or prevention of AD and other tauopathies.
