DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early...DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.展开更多
Fibrotic diseases place a substantial burden on health and the economy,with limited treatment options.Therefore,effective therapeutic strategies are urgently needed.Emodin,a natural compound with diverse biological ac...Fibrotic diseases place a substantial burden on health and the economy,with limited treatment options.Therefore,effective therapeutic strategies are urgently needed.Emodin,a natural compound with diverse biological activities,has been dem-onstrated in multiple studies over recent years to have potential therapeutic effects on fibrotic diseases.This review aims to provide a comprehensive overview of the existing research on emodin's pharmacological effects and mechanisms in inhibit-ing fibrotic disease,with a focus on its therapeutic advantages and systemic mechanisms.Recent studies have shown that emodin plays a role in combating fibrotic diseases by suppressing the production of inflammatory cytokines,such as IL-1β,IL-6,and TNF-α;it alleviates inflammation by inhibiting the NF-κB signaling pathway and preventing the degradation of IκB.Emodin also suppresses the activation of the MAPK pathway,enhances the expression of antioxidant enzymes,and influences the metabolism of the extracellular matrix(ECM).Thus,emodin is highlighted for its potential as an antifibrotic agent,and future research directions are proposed to deepen our understanding and develop novel treatment strategies for fibrotic diseases.展开更多
Intellectual disability(ID)arises from complex pathogenic mechanisms.Although myelin dysfunction and white matter damage have been implicated,the cellular and molecular mechanisms linking impaired myelination to cogni...Intellectual disability(ID)arises from complex pathogenic mechanisms.Although myelin dysfunction and white matter damage have been implicated,the cellular and molecular mechanisms linking impaired myelination to cognitive deficits remain largely unknown.Here,we identify a de novo heterogeneous nuclear ribonucleoprotein H2(HNRNPH2)variant,c.638C>T(p.Pro213Leu),in patients with ID.The Hnrnph2P213L knock-in mice display spatial learning deficits,representing a partial phenotypic overlap with HNRNPH2-related neurodevelopmental disorder.Notably,Hnrnph2P213L mice exhibit significant myelination defects,primarily due to the impaired differentiation of oligodendrocyte progenitor cells.Furthermore,the myelin-enhancing drug benztropine rescues myelination,restores myelin-related gene expression,and ameliorates cognitive deficits,highlighting the role of hnRNPH2 P213L-induced myelin abnormalities in the pathogenesis of ID.Mechanistically,the P213L mutation disrupts the interaction between hnRNPH2 and its target transcripts,leading to the downregulation of myelination-related genes.Collectively,these findings reveal a critical mechanistic connection between myelin dysfunction and ID,thereby offering potential therapeutic insights for X-linked neurodevelopmental disorders.展开更多
A novel porous CuO/Cu2O composite hollow sphere assembled with one-dimensional(1D)nanostructures was successfully synthesized by a facile one-pot surfactant and template-free hydrothermal method.The electrochemical...A novel porous CuO/Cu2O composite hollow sphere assembled with one-dimensional(1D)nanostructures was successfully synthesized by a facile one-pot surfactant and template-free hydrothermal method.The electrochemical performance evidently demonstrated that the achieved porous CuO/Cu2O composite hollow sphere was a very effective structure for solving the large volume expansion problem,which was serious issue for metal oxide anode materials.Compared to the initial cycle,the porous CuO/Cu2O composite hollow spheres maintain a high reversible capacity of 680 mAh/g after 500 cycles at 100 mA/g without capacity fading.Meanwhile,the porous CuO/Cu2O composite hollow spheres exhibit a good rate capability.The reversible capacity and cycling life significantly superior to those of reported CuO and Cu2O nanostructures as well as CuO/Cu2O composite nanostructures,and the capacity fade was significantly inhibited.The excellent electrochemical performance of the CuO/Cu2O composite hollow spheres for anode materials in lithium-ion(Li+)batteries are attributed to the efficient diffusion of Li+and electron facilitated by porous and 1D nanostructures,which promotes the diffusion of Li+and electrons,effectively mitigates the volume changes caused by mesopores and internal hollow spaces,and the synergistic effect between CuO and Cu2O within the porous CuO/Cu2O composite hollow spheres.展开更多
基金National Natural Science Foundation of China,Nos.82471264(to YL),82201392(to AZ),82071415(to JL)Shanghai Rising Stars of Medical Talents Youth Development Program,No.2023-62(to YL)+2 种基金the Shanghai Municipal Health Commission Clinical Research Special Fund for the Health Industry,No.20234Y0026(to YL)the Shanghai Sailing Program,No.22YF1425100(to AZ)Chinese Postdoctoral Science Foundation,No.2021M702169(to YJ).
摘要DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.
基金supported by the foundation of the National Conference on Undergraduate Innovation and Entrepreneurship(No.202510226099).
摘要Fibrotic diseases place a substantial burden on health and the economy,with limited treatment options.Therefore,effective therapeutic strategies are urgently needed.Emodin,a natural compound with diverse biological activities,has been dem-onstrated in multiple studies over recent years to have potential therapeutic effects on fibrotic diseases.This review aims to provide a comprehensive overview of the existing research on emodin's pharmacological effects and mechanisms in inhibit-ing fibrotic disease,with a focus on its therapeutic advantages and systemic mechanisms.Recent studies have shown that emodin plays a role in combating fibrotic diseases by suppressing the production of inflammatory cytokines,such as IL-1β,IL-6,and TNF-α;it alleviates inflammation by inhibiting the NF-κB signaling pathway and preventing the degradation of IκB.Emodin also suppresses the activation of the MAPK pathway,enhances the expression of antioxidant enzymes,and influences the metabolism of the extracellular matrix(ECM).Thus,emodin is highlighted for its potential as an antifibrotic agent,and future research directions are proposed to deepen our understanding and develop novel treatment strategies for fibrotic diseases.
基金supported by grants from the National Natural Science Foundation of China(32471018,32070967,and 32070968).
摘要Intellectual disability(ID)arises from complex pathogenic mechanisms.Although myelin dysfunction and white matter damage have been implicated,the cellular and molecular mechanisms linking impaired myelination to cognitive deficits remain largely unknown.Here,we identify a de novo heterogeneous nuclear ribonucleoprotein H2(HNRNPH2)variant,c.638C>T(p.Pro213Leu),in patients with ID.The Hnrnph2P213L knock-in mice display spatial learning deficits,representing a partial phenotypic overlap with HNRNPH2-related neurodevelopmental disorder.Notably,Hnrnph2P213L mice exhibit significant myelination defects,primarily due to the impaired differentiation of oligodendrocyte progenitor cells.Furthermore,the myelin-enhancing drug benztropine rescues myelination,restores myelin-related gene expression,and ameliorates cognitive deficits,highlighting the role of hnRNPH2 P213L-induced myelin abnormalities in the pathogenesis of ID.Mechanistically,the P213L mutation disrupts the interaction between hnRNPH2 and its target transcripts,leading to the downregulation of myelination-related genes.Collectively,these findings reveal a critical mechanistic connection between myelin dysfunction and ID,thereby offering potential therapeutic insights for X-linked neurodevelopmental disorders.
摘要A novel porous CuO/Cu2O composite hollow sphere assembled with one-dimensional(1D)nanostructures was successfully synthesized by a facile one-pot surfactant and template-free hydrothermal method.The electrochemical performance evidently demonstrated that the achieved porous CuO/Cu2O composite hollow sphere was a very effective structure for solving the large volume expansion problem,which was serious issue for metal oxide anode materials.Compared to the initial cycle,the porous CuO/Cu2O composite hollow spheres maintain a high reversible capacity of 680 mAh/g after 500 cycles at 100 mA/g without capacity fading.Meanwhile,the porous CuO/Cu2O composite hollow spheres exhibit a good rate capability.The reversible capacity and cycling life significantly superior to those of reported CuO and Cu2O nanostructures as well as CuO/Cu2O composite nanostructures,and the capacity fade was significantly inhibited.The excellent electrochemical performance of the CuO/Cu2O composite hollow spheres for anode materials in lithium-ion(Li+)batteries are attributed to the efficient diffusion of Li+and electron facilitated by porous and 1D nanostructures,which promotes the diffusion of Li+and electrons,effectively mitigates the volume changes caused by mesopores and internal hollow spaces,and the synergistic effect between CuO and Cu2O within the porous CuO/Cu2O composite hollow spheres.