Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a stro...BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus,the pathogenesis of SCI is still under investigation.AIM To determine the key genes based on the modularization of in-depth analysis,in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI.METHODS Firstly,the differences between injured and non-injured spinal cord of astrocyte(HA),injured and non-injured spinal cord of non-astrocyte(FLOW),injured spinal cord of non-injured astrocyte(HA)and non-injured spinal cord of nonastrocyte(FLOW),and non-injured spinal cord of astrocyte(HA)and nonastrocyte(FLOW)were analyzed.The total number of differentially expressed genes was obtained by merging the four groups of differential results.Secondly,the genes were co-expressed and clustered.Then,the enrichment of GO function and KEGG pathway of module genes was analyzed.Finally,non-coding RNA,transcription factors and drugs that regulate module genes were predicted using hypergeometric tests.RESULTS In summary,we obtained 19 expression modules involving 5216 differentially expressed genes.Among them,miR-494,XIST and other genes were differentially expressed in SCI patients,and played an active regulatory role in dysfunction module,and these genes were recognized as the driving genes of SCI.Enrichment results showed that module genes were significantly involved in the biological processes of inflammation,oxidation and apoptosis.Signal pathways such as NF-kappa B/A20,AMPK and MAPK were significantly regulated.In addition,non-coding RNA pivot(including miR-136-5p and let-7d-5p,etc.)and transcription factor pivot(including NFKB1,MYC,etc.)were identified as significant regulatory dysfunction modules.CONCLUSION Overall,this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI.These findings helped to reveal the core dysfunction modules,potential regulatory factors and driving genes of the disease,and to improve our understanding of its pathogenesis.展开更多
Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neur...Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.展开更多
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
文摘BACKGROUND Spinal cord injury(SCI)is a destructive disease that incurs huge personal and social costs,and there is no effective treatment.Although the pathogenesis and treatment mechanism of SCI has always been a strong scientific focus,the pathogenesis of SCI is still under investigation.AIM To determine the key genes based on the modularization of in-depth analysis,in order to identify the repair mechanism of astrocytes and non-astrocytes in SCI.METHODS Firstly,the differences between injured and non-injured spinal cord of astrocyte(HA),injured and non-injured spinal cord of non-astrocyte(FLOW),injured spinal cord of non-injured astrocyte(HA)and non-injured spinal cord of nonastrocyte(FLOW),and non-injured spinal cord of astrocyte(HA)and nonastrocyte(FLOW)were analyzed.The total number of differentially expressed genes was obtained by merging the four groups of differential results.Secondly,the genes were co-expressed and clustered.Then,the enrichment of GO function and KEGG pathway of module genes was analyzed.Finally,non-coding RNA,transcription factors and drugs that regulate module genes were predicted using hypergeometric tests.RESULTS In summary,we obtained 19 expression modules involving 5216 differentially expressed genes.Among them,miR-494,XIST and other genes were differentially expressed in SCI patients,and played an active regulatory role in dysfunction module,and these genes were recognized as the driving genes of SCI.Enrichment results showed that module genes were significantly involved in the biological processes of inflammation,oxidation and apoptosis.Signal pathways such as NF-kappa B/A20,AMPK and MAPK were significantly regulated.In addition,non-coding RNA pivot(including miR-136-5p and let-7d-5p,etc.)and transcription factor pivot(including NFKB1,MYC,etc.)were identified as significant regulatory dysfunction modules.CONCLUSION Overall,this study uncovered a co-expression network of key genes involved in astrocyte and non-astrocyte regulation in SCI.These findings helped to reveal the core dysfunction modules,potential regulatory factors and driving genes of the disease,and to improve our understanding of its pathogenesis.
文摘Deep brain sti mulation(DBS)is a neuromodulation tool that involves the delivery of electrical impulses to specific brain regions through implanted electrodes.The principle behind DBS is to modulate dysfunctional neural circuits without the need for permanent structural alterations to the brain.Initially developed as a treatment for movement disorders such as Parkinson's disease(PD),DBS has expanded to encompass various neurological and psychiatric disorders.
