There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progre...There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.展开更多
We study afresh how the glucose control system anomalies impact the organicity of the glucose homeostasis and build up events of persistent hyperglycemia and diabetes mellitus. We have used critically the state of art...We study afresh how the glucose control system anomalies impact the organicity of the glucose homeostasis and build up events of persistent hyperglycemia and diabetes mellitus. We have used critically the state of art literature related to the subject, in order to cross, to compare, and to organize the relevant contents to create a logical and consistent support to the finds. We show that it is consistent to assume that persistent hyperglycemia and diabetes mellitus can have precursors not only in pancreas, but also in brain, mainly induced by noxious dysfunctions of hypothalamus sensor neurons circuits and external noxious elements, causing pancreas overload, and the consequent exhaustion—overburden.展开更多
Multiple sclerosis is a chronic companied by demyelination inflammatory disease that is ac- and axonal damage resulting in neurological deficits. Remyelination is the natural endogenous repair mechanism of demyelinate...Multiple sclerosis is a chronic companied by demyelination inflammatory disease that is ac- and axonal damage resulting in neurological deficits. Remyelination is the natural endogenous repair mechanism of demyelinated axons and it is supposed to protect axons/neurons from degeneration and thus the patient from progressive disability （Franklin and Ffrench-Constant, 2008）. Current therapeutics for patients with multiple sclerosis are to some extent very effective in inhibiting neuroinflamma- tion and demyelination. However, to date there are no substanc- es available that can enhance remyelination. Remyelination is the result of recruitment/proliferation of new oligodendrocyte precursor cells （OPC） and differentiation into mature myelin producing oligodendrocytes （Franklin and Ffrench-Constant, 2008）. These processes are supported by many factors and signals and failure at any stage might lead to repair failure. Strategies to enhance myelin repair are either the promotion of endogenous repair mechanisms via modulation of OPC prolif- eration and oligodendrocyte differentiation or the transplantion of myelinating cells into lesions. Due to the multiloculated pro- cess in multiple sclerosis and the ethical problems with the cell source, the latter is less favoured. The endogenous promotion of remvelination could be achieved by several approaches such as：展开更多
Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache diso...Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache disorders,multiple sclerosis,Parkinson＇s disease,and neuroinfections）.展开更多
In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.A...In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.展开更多
Polyphenolic compounds have received tremendous attention in biomedicine because of their good biocompatibility and unique physicochemical properties.In recent years,phenolic-enabled nanotechnology(PEN)has become a ho...Polyphenolic compounds have received tremendous attention in biomedicine because of their good biocompatibility and unique physicochemical properties.In recent years,phenolic-enabled nanotechnology(PEN)has become a hotspot of research in the medical field,and many promising studies have been reported,especially in the application of central nervous system(CNS)diseases.Polyphenolic compounds have superior anti-inflammatory and antioxidant properties,and can easily cross the blood‒brain barrier,as well as protect the nervous system from metabolic damage and promote learning and cognitive functions.However,although great advances have been made in this field,a comprehensive review regarding PEN-based nanomaterials for CNS therapy is lacking.A systematic summary of the basic mechanisms and synthetic strategies of PEN-based nanomaterials is beneficial for meeting the demand for the further development of novel treatments for CNS diseases.This review systematically introduces the fundamental physicochemical properties of PEN-based nanomaterials and their applications in the treatment of CNS diseases.We first describe the different ways in which polyphenols interact with other substances to form high-quality products with controlled sizes,shapes,compositions,and surface chemistry and functions.The application of PEN-based nanomaterials in the treatment of CNS diseases is then described,which provides a reference for subsequent research on the treatment of CNS diseases.展开更多
Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin in...Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin inhibition (Fischer, 2012). Even in the PNS, which has the principle ability to regenerate injured axons, functional recovery remains limited, particularly in cases where the nerve target has become unreceptive to re-innervation over time due to an insufficient axonal growth rate (Diekmann and Fischer, 2015). Progress towards robust neuroregenerative therapies depends upon an understanding of the relevant signaling and cytoskeletal proteins that drive and control axon extension. Muscle LIM protein (MLP), also known as cysteine and glycine-rich protein 3, was recently discovered to be one such protein that is expressed in regenerating rat neurons and whose overexpression can promote the axon regeneration of adult central, and peripheral neurons of different species (Levin et al., 2019).展开更多
Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been d...Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been described. On the other hand, CNS demyelinating lesions and cervical atrophy have been re- ported in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Very few cases of MGUS associated with CNS disease alone or with both CNS and PNS disease have been re- ported. Since 1999, we have been studying 16 patients (8 M, 8 F), with a mean age 60.2 ± 13.4, affected by MGUS associated with symptomatic neurological central and/or peripheral diseases. Patients affected with lymphomas, lupus erithematosus and other immunological diseases were excluded. Involvement of both PNS and CNS was not associated to a particular type of paraproteinemia: monoclonal IgM were found in 8 patients;monoclonal IgG in 6 patients and mono- clonal IgA in 1 patient and Igl in 1 patient. High anti- nervous system autoantibodies were found in 10/16 patients and antiMAG antibodies were detected in patients with paraproteinemic demyelinating neuropathy (PDN). High reactivity anti-nervous system might support the hypothesis of a pathogenetic role of MGUS in these neurological diseases. Nevertheless, at present, we cannot exclude that there is only a circumstantial association between MGUS and neurological damages, particularly concerning CNS.展开更多
Jnurnal of Cenntral South University(CN 43一1516/TB, ISSN 2095-2899) (formerly named Journal of Central South University Technology,CN 43-1231/TD, ISSN 1005-9784) is a comprehensive academic English journal,
文摘There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.
文摘We study afresh how the glucose control system anomalies impact the organicity of the glucose homeostasis and build up events of persistent hyperglycemia and diabetes mellitus. We have used critically the state of art literature related to the subject, in order to cross, to compare, and to organize the relevant contents to create a logical and consistent support to the finds. We show that it is consistent to assume that persistent hyperglycemia and diabetes mellitus can have precursors not only in pancreas, but also in brain, mainly induced by noxious dysfunctions of hypothalamus sensor neurons circuits and external noxious elements, causing pancreas overload, and the consequent exhaustion—overburden.
文摘Multiple sclerosis is a chronic companied by demyelination inflammatory disease that is ac- and axonal damage resulting in neurological deficits. Remyelination is the natural endogenous repair mechanism of demyelinated axons and it is supposed to protect axons/neurons from degeneration and thus the patient from progressive disability （Franklin and Ffrench-Constant, 2008）. Current therapeutics for patients with multiple sclerosis are to some extent very effective in inhibiting neuroinflamma- tion and demyelination. However, to date there are no substanc- es available that can enhance remyelination. Remyelination is the result of recruitment/proliferation of new oligodendrocyte precursor cells （OPC） and differentiation into mature myelin producing oligodendrocytes （Franklin and Ffrench-Constant, 2008）. These processes are supported by many factors and signals and failure at any stage might lead to repair failure. Strategies to enhance myelin repair are either the promotion of endogenous repair mechanisms via modulation of OPC prolif- eration and oligodendrocyte differentiation or the transplantion of myelinating cells into lesions. Due to the multiloculated pro- cess in multiple sclerosis and the ethical problems with the cell source, the latter is less favoured. The endogenous promotion of remvelination could be achieved by several approaches such as：
文摘Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache disorders,multiple sclerosis,Parkinson＇s disease,and neuroinfections）.
基金supported by the National Natural Science Foundation of China(Nos.82073366 and 32100748)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18007)the National Natural Science Foundation of Sichuan Province(No.2022NSFSC1642).
文摘In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.
基金supported by the National Natural Science Foundation of China(No.82273861)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(CAST)(No.YESS20220139).
文摘Polyphenolic compounds have received tremendous attention in biomedicine because of their good biocompatibility and unique physicochemical properties.In recent years,phenolic-enabled nanotechnology(PEN)has become a hotspot of research in the medical field,and many promising studies have been reported,especially in the application of central nervous system(CNS)diseases.Polyphenolic compounds have superior anti-inflammatory and antioxidant properties,and can easily cross the blood‒brain barrier,as well as protect the nervous system from metabolic damage and promote learning and cognitive functions.However,although great advances have been made in this field,a comprehensive review regarding PEN-based nanomaterials for CNS therapy is lacking.A systematic summary of the basic mechanisms and synthetic strategies of PEN-based nanomaterials is beneficial for meeting the demand for the further development of novel treatments for CNS diseases.This review systematically introduces the fundamental physicochemical properties of PEN-based nanomaterials and their applications in the treatment of CNS diseases.We first describe the different ways in which polyphenols interact with other substances to form high-quality products with controlled sizes,shapes,compositions,and surface chemistry and functions.The application of PEN-based nanomaterials in the treatment of CNS diseases is then described,which provides a reference for subsequent research on the treatment of CNS diseases.
基金supported by the German Research Foundation(FI 867/12,to DF)
文摘Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin inhibition (Fischer, 2012). Even in the PNS, which has the principle ability to regenerate injured axons, functional recovery remains limited, particularly in cases where the nerve target has become unreceptive to re-innervation over time due to an insufficient axonal growth rate (Diekmann and Fischer, 2015). Progress towards robust neuroregenerative therapies depends upon an understanding of the relevant signaling and cytoskeletal proteins that drive and control axon extension. Muscle LIM protein (MLP), also known as cysteine and glycine-rich protein 3, was recently discovered to be one such protein that is expressed in regenerating rat neurons and whose overexpression can promote the axon regeneration of adult central, and peripheral neurons of different species (Levin et al., 2019).
文摘Several studies have suggested a pathogenetic role of paraproteinaemias in PNS damage. Over the few last years, the presence of symptomatic or subclinical PNS lesions in CNS diseases like multiple sclerosis has been described. On the other hand, CNS demyelinating lesions and cervical atrophy have been re- ported in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Very few cases of MGUS associated with CNS disease alone or with both CNS and PNS disease have been re- ported. Since 1999, we have been studying 16 patients (8 M, 8 F), with a mean age 60.2 ± 13.4, affected by MGUS associated with symptomatic neurological central and/or peripheral diseases. Patients affected with lymphomas, lupus erithematosus and other immunological diseases were excluded. Involvement of both PNS and CNS was not associated to a particular type of paraproteinemia: monoclonal IgM were found in 8 patients;monoclonal IgG in 6 patients and mono- clonal IgA in 1 patient and Igl in 1 patient. High anti- nervous system autoantibodies were found in 10/16 patients and antiMAG antibodies were detected in patients with paraproteinemic demyelinating neuropathy (PDN). High reactivity anti-nervous system might support the hypothesis of a pathogenetic role of MGUS in these neurological diseases. Nevertheless, at present, we cannot exclude that there is only a circumstantial association between MGUS and neurological damages, particularly concerning CNS.
文摘Jnurnal of Cenntral South University(CN 43一1516/TB, ISSN 2095-2899) (formerly named Journal of Central South University Technology,CN 43-1231/TD, ISSN 1005-9784) is a comprehensive academic English journal,
文摘侵袭性真菌病(invasive fungal disease,IFD)是异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)术后常见并发症,最常见致病菌为念珠菌和曲霉菌。近些年来,中枢神经系统真菌感染(fungal infections of the central nervous system,FIs-CNS)发病率逐渐增加,治疗难度大.
