Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers im...Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.展开更多
Macrophages are typically identified as classically activated(M1) macrophages and alternatively activated(M2) macrophages,which respectively exhibit pro-and anti-inflammatory phenotypes,and the balance between these t...Macrophages are typically identified as classically activated(M1) macrophages and alternatively activated(M2) macrophages,which respectively exhibit pro-and anti-inflammatory phenotypes,and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation,injury,and repair processes.Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles(EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury and vice versa.This review discusses the roles of such EVs in resulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions,and the potential applications,advantage and concerns for using EV-based therapeutic approaches to treat such conditions,including their potential role of drug carriers for the treatment of infectious diseases.展开更多
The present review has been designed to update the recent developments on the function of seminal vesicles andtheir role on male fertility. It is indicated that the true corrected fructose level is a simple method for...The present review has been designed to update the recent developments on the function of seminal vesicles andtheir role on male fertility. It is indicated that the true corrected fructose level is a simple method for the assessment ofthe seminal vesicular function. Measurement of seminal fructose used universally as a marker of the seminal vesiclefunction is not an appropriate approach due to its inverse relationship with the sperm count. The true corrected fructosedefined as [log. motile sperm concentration] multiplied by [seminal fructose concentration] has been shown to be abetter marker of the seminal vesicle function. Seminal vesicular secretion is important for semen coagulation, sperm motility, and stability of sperm chromatinand suppression of the immune activity in the female reproductive tract. In conclusion, the function of seminal vesicle is important for fertility. Parameters as sperm motility, sperm chro-matin stability, and immuno-protection may be changed in case of its hypofunction. (Asian J Androl 2001 Dec; 3:251 -258)展开更多
Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease,...Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease, Parkinson＇s disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in ...Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.展开更多
Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of...Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.展开更多
Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not ...Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not been attained.Recently,exosomes have gained significant attention due to the therapeutic potential of their various components including proteins,lipids,nucleic acids,miRNAs,and lncRNAs.Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm.They are released from different cells and are present in biofluids including blood,cerebrospinal fluid(CSF),and urine.They perform crucial multifaceted functions in the malignant progression of cancer via autocrine,paracrine,and endocrine communications.The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics.In this review,we discuss the major components of exosomes and their role in cancer progression.We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.展开更多
Extracellular vesicles （EVs） are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cell-cell...Extracellular vesicles （EVs） are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cell-cell communication and signalling, particularly between immune cells. EV research is a rapidly evolving and expanding field, and it appears that all biological fluids contain very large numbers of EVs; they are produced from all cells that have been studied to date, and are known to have roles in several reproductive processes. This review analyses the evidence for the role of EVs throughout human reproduction, starting with the paternal and maternal gametes, followed by the establishment and continuation of successful pregnancies, with specific focus, where possible, on the interaction of EVs with the maternal immune system. Importantly, variations within the EV populations are identified in various reproductive disorders, such as pre-term labour and pre-eclampsia.展开更多
Objective： Diabetic kidney disease （DKD） has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles （uEVs） contain rich biological information which could be the ideal source fo...Objective： Diabetic kidney disease （DKD） has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles （uEVs） contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD. Data Sources： This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords： ＂Diabetic kidney disease＂, ＂Extracellular vesicle＂, and ＂Urine＂. Study Selection： Relevant articles were carefully reviewed, with no exclusions applied to tile study design and publication type. Results： There is no ＂gold standard＂ technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD. Conclusion： Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.展开更多
Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central n...Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.展开更多
Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine fac...Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles(EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique antiinflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.展开更多
In this paper, the self-assembly of PS 43-b-PEO 45-b-PS 43 triblcok copolymer was investigated. The colloids were made by firstly dissolving the copolymer in the common solvents, including THF, 1,4-dioxane, and DMF, t...In this paper, the self-assembly of PS 43-b-PEO 45-b-PS 43 triblcok copolymer was investigated. The colloids were made by firstly dissolving the copolymer in the common solvents, including THF, 1,4-dioxane, and DMF, then droping water into the corresponding copolymer solution to induce the self-assembly. The aggregates prepared were characterized with TEM and AFM techniques. The experimental results demonstrated that the self-assembled vesicles were formed when THF and 1,4-dioxane were used as the common solvents to dissolve the copolymer, comparatively, using DMF as the common solvent resulted in the formation of spherical aggregates. The self-assembled aggregates observed, possessing hierarchical structures, could be used as either the nanostructures themselves for drug delivery systems, separations, catalysts, and so on, or templates or building blocks for more complex structures.展开更多
Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its h...Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases.展开更多
The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem c...The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.展开更多
The aim of this study was to evaluate the ultrasound characteristics of the seminal vesicles （SVs） of infertile patients with diabetes mellitus （DM） and diabetic neuropathy （DN） and to investigate possible chang...The aim of this study was to evaluate the ultrasound characteristics of the seminal vesicles （SVs） of infertile patients with diabetes mellitus （DM） and diabetic neuropathy （DN） and to investigate possible changes in ultrasound characteristics related to glycaemic control. To accomplish this, 45 infertile patients with type 2 DM and symptomatic DN were selected. Twenty healthy fertile men and 20 patients with idiopathic oligoasthenoteratozoospermia without DM represented the control groups. DM patients were arbitrarily divided into three groups according to glycaemic control level （A=glycosylated haemoglobin 〈7%; B =glycosylated haemoglobin between 7% and 10%; C=glycosylated haemoglobin 〉 10%）. Patients underwent prostate-vesicular transrectal ultrasonography and sperm analysis. The following SV ultrasound parameters were recorded： （i） body antero-posterior diameter （APD）; （ii） fundus APD; （iii） parietal thicknesses of the right and left SVs; and （iv） the number of polycyclic areas within both SVs. We then calculated the following parameters： （i） fundus/body （F/B） ratio; （ii） difference of the parietal thickness between the right and the left SV; and （iii） pre- and post-ejaculatory APD difference. All DM patients had a higher FIB ratio compared to controls （P〈0.05）. Group C had a higher FIB ratio compared to the other DM groups （P〈0.05）. All DM patients had a lower pre- and post-ejaculatory difference of the body SV APD compared to controls （P〈0.05）. Groups A and B had a similar pre- and post-ejaculatory difference of the body SV APD, whereas this difference was lower in Group C （P〈0.05）. In conclusion, infertile DM patients with DN showed peculiar SV ultrasound features suggestive of functional atony, and low glycaemic control was associated with greater expression of these features.展开更多
文摘Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.
基金the support from Weatherhead Presidential Endowment Fund (USA)。
文摘Macrophages are typically identified as classically activated(M1) macrophages and alternatively activated(M2) macrophages,which respectively exhibit pro-and anti-inflammatory phenotypes,and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation,injury,and repair processes.Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles(EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury and vice versa.This review discusses the roles of such EVs in resulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions,and the potential applications,advantage and concerns for using EV-based therapeutic approaches to treat such conditions,including their potential role of drug carriers for the treatment of infectious diseases.
文摘The present review has been designed to update the recent developments on the function of seminal vesicles andtheir role on male fertility. It is indicated that the true corrected fructose level is a simple method for the assessment ofthe seminal vesicular function. Measurement of seminal fructose used universally as a marker of the seminal vesiclefunction is not an appropriate approach due to its inverse relationship with the sperm count. The true corrected fructosedefined as [log. motile sperm concentration] multiplied by [seminal fructose concentration] has been shown to be abetter marker of the seminal vesicle function. Seminal vesicular secretion is important for semen coagulation, sperm motility, and stability of sperm chromatinand suppression of the immune activity in the female reproductive tract. In conclusion, the function of seminal vesicle is important for fertility. Parameters as sperm motility, sperm chro-matin stability, and immuno-protection may be changed in case of its hypofunction. (Asian J Androl 2001 Dec; 3:251 -258)
文摘Traumatic brain injury （TBI） remains a major cause of death and disability worldwide, Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer＇s disease, Parkinson＇s disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.
基金supported by the National Natural Science Foundation of China(Nos.81673022,81572952 and 81373346)National Key R&D Program of China(No.2017YFE0102200)
文摘Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
基金supported by National Cancer Institute(NCI)R00 CA226353-01A1Cancer Research Foundation Young Investigator Award to HJC+2 种基金Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)grant(309380/2019-7)Fundacao de Amparoa Pesquisa do Estado de Sao Paulo(FAPESP)(2017/10051-2)to MBa fellowship supported by CNPq grant(133306/2019-4)during the development of this work.
文摘Cancer is a deadly disease that is globally and consistently one of the leading causes of mortality every year.Despite the availability of chemotherapy,radiotherapy,immunotherapy,and surgery,a cure for cancer has not been attained.Recently,exosomes have gained significant attention due to the therapeutic potential of their various components including proteins,lipids,nucleic acids,miRNAs,and lncRNAs.Exosomes constitute a set of tiny extracellular vesicles with an approximate diameter of 30-100 nm.They are released from different cells and are present in biofluids including blood,cerebrospinal fluid(CSF),and urine.They perform crucial multifaceted functions in the malignant progression of cancer via autocrine,paracrine,and endocrine communications.The ability of exosomes to carry different cargoes including drug and molecular information to recipient cells make them a novel tool for cancer therapeutics.In this review,we discuss the major components of exosomes and their role in cancer progression.We also review important literature about the potential role of exosomes as vaccines and delivery carriers in the context of cancer therapeutics.
文摘Extracellular vesicles （EVs） are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cell-cell communication and signalling, particularly between immune cells. EV research is a rapidly evolving and expanding field, and it appears that all biological fluids contain very large numbers of EVs; they are produced from all cells that have been studied to date, and are known to have roles in several reproductive processes. This review analyses the evidence for the role of EVs throughout human reproduction, starting with the paternal and maternal gametes, followed by the establishment and continuation of successful pregnancies, with specific focus, where possible, on the interaction of EVs with the maternal immune system. Importantly, variations within the EV populations are identified in various reproductive disorders, such as pre-term labour and pre-eclampsia.
基金This study was supported by grants from the Guangdong Provincial Science and Technology Project （No. 2014A020212662）, the Science and Technology Planning Project of Southern Medical University （No. CX2016N018）, the Science and Technology Planning Project of Tianhe District, Guangzhou City （No. 201704KW011）, The Natural Science Foundation of Guangdong Province （2016A030313559）, and The South Wisdom Valley Innovative Research Team Program （No. CXTD-004, 2014）.
文摘Objective： Diabetic kidney disease （DKD） has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles （uEVs） contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD. Data Sources： This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords： ＂Diabetic kidney disease＂, ＂Extracellular vesicle＂, and ＂Urine＂. Study Selection： Relevant articles were carefully reviewed, with no exclusions applied to tile study design and publication type. Results： There is no ＂gold standard＂ technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD. Conclusion： Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.
基金financially supported by the Russian Government Program of Competitive Growth of Kazan Federal Universitysupported by state assignment 20.5175.2017/6.7 of the Ministry of Education and Science of Russian Federationthe President of the Russian Federation grant НШ-3076.2018.4
文摘Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems.In many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic proteins.The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases.Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier.Today,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUS,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well evidenced.Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative diseases.Depending on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and anti-inflammatory.Due to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain.This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.
基金National Natural Science Foundation of China,No.81800825,No.81870651 and No.81870675。
文摘Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles(EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique antiinflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.
文摘In this paper, the self-assembly of PS 43-b-PEO 45-b-PS 43 triblcok copolymer was investigated. The colloids were made by firstly dissolving the copolymer in the common solvents, including THF, 1,4-dioxane, and DMF, then droping water into the corresponding copolymer solution to induce the self-assembly. The aggregates prepared were characterized with TEM and AFM techniques. The experimental results demonstrated that the self-assembled vesicles were formed when THF and 1,4-dioxane were used as the common solvents to dissolve the copolymer, comparatively, using DMF as the common solvent resulted in the formation of spherical aggregates. The self-assembled aggregates observed, possessing hierarchical structures, could be used as either the nanostructures themselves for drug delivery systems, separations, catalysts, and so on, or templates or building blocks for more complex structures.
文摘Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases.
基金Supported by Grants from the State Key Projects for Basic Re-search,No.2011CB910703 and No.2012ZX10002-017(to Zhao XH)National High-tech R and D Program,No.2013AA041201(to Qian YM)and No.2012AA020206(to Zhao XH)+1 种基金National Natural Science Foundation of China,No.81372591 and No.81321091(to Zhao XH)the Research Foundation of the Center for Marine Medicine and Rescue of Tsinghua University and NGH(to Qian YM and Zhao XH)
文摘AIM: To develop a novel method for the rapid and efficient extraction of exosomes secreted by tumor cells.
基金supported by National Natural Science Foundation of China(Grant No.51872224,81772379,81972096 and 81902238)Zhejiang Province Health Foundation,China(Grant No.2018KY092,WKJ-ZJ-1903)Nature Science Foundation of Zhejiang Province,China(Grant No.LQ18H060003).
文摘The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.
文摘The aim of this study was to evaluate the ultrasound characteristics of the seminal vesicles （SVs） of infertile patients with diabetes mellitus （DM） and diabetic neuropathy （DN） and to investigate possible changes in ultrasound characteristics related to glycaemic control. To accomplish this, 45 infertile patients with type 2 DM and symptomatic DN were selected. Twenty healthy fertile men and 20 patients with idiopathic oligoasthenoteratozoospermia without DM represented the control groups. DM patients were arbitrarily divided into three groups according to glycaemic control level （A=glycosylated haemoglobin 〈7%; B =glycosylated haemoglobin between 7% and 10%; C=glycosylated haemoglobin 〉 10%）. Patients underwent prostate-vesicular transrectal ultrasonography and sperm analysis. The following SV ultrasound parameters were recorded： （i） body antero-posterior diameter （APD）; （ii） fundus APD; （iii） parietal thicknesses of the right and left SVs; and （iv） the number of polycyclic areas within both SVs. We then calculated the following parameters： （i） fundus/body （F/B） ratio; （ii） difference of the parietal thickness between the right and the left SV; and （iii） pre- and post-ejaculatory APD difference. All DM patients had a higher FIB ratio compared to controls （P〈0.05）. Group C had a higher FIB ratio compared to the other DM groups （P〈0.05）. All DM patients had a lower pre- and post-ejaculatory difference of the body SV APD compared to controls （P〈0.05）. Groups A and B had a similar pre- and post-ejaculatory difference of the body SV APD, whereas this difference was lower in Group C （P〈0.05）. In conclusion, infertile DM patients with DN showed peculiar SV ultrasound features suggestive of functional atony, and low glycaemic control was associated with greater expression of these features.
