Emodin(1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum ...Emodin(1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.展开更多
Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbat...Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and xenobiotics.These effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions.Besides,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration disorder.In this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.展开更多
Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammat...Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.展开更多
Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bite...Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.展开更多
AIM： The treatment of liver disease is severely limited by a shortage of donor livers. In trying to address this growing problem, hepatocellular transplantation （HTx） has received much attention as an alternative t...AIM： The treatment of liver disease is severely limited by a shortage of donor livers. In trying to address this growing problem, hepatocellular transplantation （HTx） has received much attention as an alternative to whole organ transplant. However, the expansion of transplanted cells is at low level, and the reconstitution of functional liver tissue is limited by this cellular property. We set up an animal model to better understand cell dose effect and the kinetics of liver repopulation following HTx. METHODS： Dipeptidyl peptidase Ⅳ （DPPⅣ）-deficient rats treated with retrorsine and subjected to partial hepatectomy were infused with DPPⅣ-positive hepatocytes. Rats were injected with varying numbers of donor hepatocytes down to 100 cells low, and liver repopulation was examined at different time points up to 20 mo long. Repopulation was assessed by computer-aided quantitative detection. RESULTS： Transplanted hepatocytes underwent multiple rounds of proliferation and stably repopulated the injured livers after 20 mo and at all cell doses. Transplanted cells divided 14 times within the 3-mo time period following infusion, and the liver repopulation reached a plateau between 3 and 20 too. Approximately 90% replacement occurred. Donor-derived cells also reconstituted the bile ductules of the recipients. CONCLUSION： The ability of transplanted hepatocytes to fully reconstitute injured livers strongly supports further investigation into the clinical potential of HTx. Additionally, the observation that transplanted hepatocytes also form components of the biliary system suggests that these cells may have bi-potential property of the stem cells.展开更多
Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response.Each inflammasome complex has three major components:an upstream sensor molecu...Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response.Each inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein ASC.Inflammasome formation typically occurs in response to infectious agents or cellular damage.The active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death.Aberrant inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative disorders.As a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various diseases.Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies.Therefore,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies.In this article,we provide a summary of the biological and pathological roles of inflammasomes in health and disease.We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.展开更多
Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood gluco...Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood glucose levels independently of insulin is well-documented. Beyond glycemic control, emerging research has unveiled their profound cardiorenal benefits. By inhibiting SGLT-2 protein, these drugs enhance glucose excretion in urine, reducing blood glucose levels. This mechanism has translated into significant cardiovascular and renal protection, establishing SGLT-2 inhibitors as pivotal in managing not only diabetes but also cardiovascular and renal diseases. Recent studies have illuminated the broader therapeutic potential of SGLT-2 inhibitors beyond diabetes. Evidence indicates their efficacy in managing heart failure, chronic kidney disease (CKD), and cardiovascular complications in individuals with or without diabetes. This expanded therapeutic landscape has catalyzed a paradigm shift in SGLT-2 inhibitor use, positioning them as key agents in the cardiorenal metabolic continuum. Moreover, their role in the secondary prevention of cardiovascular events and slowing CKD progression in T2DM patients has garnered considerable attention. This consensus-based review aims to offer practical guidance in an algorithmic approach to primary care healthcare professionals to optimize SGLT-2 inhibitors utilization and maximize their benefits. The review seeks to empower clinicians to effectively manage patients who may benefit from SGLT-2 inhibitor therapy by addressing common initiation barriers and optimizing treatment strategies. Additionally, it aims to raise awareness among primary care physicians regarding the multifaceted benefits of these medications and overcome clinical inertia in their adoption into routine clinical practice.展开更多
The aim of this review was to evaluate the therapeutic potential of exosomes, extracellular vesicles secreted by cells. They have emerged as potential therapeutic transporters for several diseases. This review provide...The aim of this review was to evaluate the therapeutic potential of exosomes, extracellular vesicles secreted by cells. They have emerged as potential therapeutic transporters for several diseases. This review provides an overview of exosomes’ therapeutic potential in cancer therapy and autoimmune conditions such as Coeliac Disease. The therapeutic effect is that the phospholipid-binding protein ANXA1 improves its anti-inflammatory properties. The review also analyzes the intricate processes of exosome production and composition ability to transport biomolecules such as proteins, microRNAs, and lipids, which promote intercellular communication and alter recipient cell behavior. Exosomes, linked to neurological disorders, cardiovascular disease, and cancer, present the means of targeted drug administration due to their innate specificity. Through genetic engineering and chemical modifications, exosomes can be tailored for specific purposes, demonstrating their versatility in targeted therapy. With ongoing research uncovering their therapeutic potential, exosomes present a promising frontier in novel medical treatments across various health conditions.展开更多
Exosomes are nanovesicles secreted from various types of cells and can be isolated from various bodily fluids, such as blood and urine. The number and molecular contents, including proteins and RNA of exosomes, have b...Exosomes are nanovesicles secreted from various types of cells and can be isolated from various bodily fluids, such as blood and urine. The number and molecular contents, including proteins and RNA of exosomes, have been shown to reflect their parental cell origins, characteristics and biological behaviors. An increasing number of studies have demonstrated that exosomes play a role in the course of tumorigenesis, diagnosis, treatment and prognosis, although its precise functions in tumors are still unclear. Moreover, owing to a lack of a standard approach, exosomes and its contents have not yet been put into clinical practice successfully. This review aims to summarize the current knowledge on exosomes and its contents in esophageal cancer as well as the current limitations/challenges in its clinical application, which may provide a basis for an all-around understanding of the implementation of exosomes and exosomal contents in the surveillance and therapy of esophageal cancer.展开更多
Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,esp...Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems.展开更多
In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which partici...In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.展开更多
Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promisin...Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promising for the therapy of these diseases.We have conceptualized a strategy,named dephosphorylation-targeting chimeras(DEPTACs),for specifically hijacking phosphatases to tau to debilitate its hyperphosphorylation.Here,we conducted the step-by-step optimization of each constituent motif to generate DEPTACs with reasonable effectiveness in facilitating the dephosphorylation and subsequent clearance of pathological tau.Specifically,for one of the selected chimeras,D16,we demonstrated its significant efficiency in rescuing the neurodegeneration caused by neurotoxic K18-tau seeds in vitro.Moreover,intravenous administration of D16 also alleviated tau pathologies in the brain and improved memory deficits in AD mice.These results suggested DEPTACs as targeted modulators of tau phosphorylation,which hold therapeutic potential for AD and other tauopathies.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and obesity.On the basis of the insights provided by Jiang et al,this editorial presents an explor...Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and obesity.On the basis of the insights provided by Jiang et al,this editorial presents an exploration of the potential of mesenchymal stem cells(MSCs)for NAFLD treatment.MSCs have numerous desirable characteristics,including immunomodulation,anti-inflammatory pro-perties,and tissue regeneration promotion,rendering them attractive candidates for NAFLD treatment.Recent preclinical and early clinical studies have high-lighted the efficacy of MSCs in improving liver function and reducing disease severity in NAFLD models.However,MSC heterogeneity,long-term safety concerns,and unoptimized therapeutic protocols remain substantial challenges.Addressing these challenges through standardized protocols and rigorous clinical trials is essential to the safe and successful application of MSCs in NAFLD mana-gement.Continued research into MSC mechanisms and therapeutic optimization is required to improve treatments for NAFLD and related liver diseases.展开更多
基金the National Natural Science Foundation of China(Nos.31370992,3167040349,31670951,3197100408)the Project of the Science and Technology Department in Sichuan Province(No.2017JY0228)。
文摘Emodin(1, 3, 8-trihydroxy-6-methylanthraquinone) is a derived anthraquinone compound extracted from roots and barks of pharmaceutical plants, including Rheum palmatum, Aloe vera, Giant knotweed, Polygonum multiflorum and Polygonum cuspidatum. The review aims to provide a scientific summary of emodin in pharmacological activities and toxicity in order to identify the therapeutic potential for its use in human specific organs as a new medicine. Based on the fundamental properties, such as anticancer, anti-inflammatory, antioxidant, antibacterial, antivirs, anti-diabetes, immunosuppressive and osteogenesis promotion, emodin is expected to become an effective preventive and therapeutic drug of cancer, myocardial infarction, atherosclerosis, diabetes, acute pancreatitis, asthma, periodontitis, fatty livers and neurodegenerative diseases. This article intends to provide a novel insight for further development of emodin, hoping to reveal the potential of emodin and necessity of further studies in this field.
基金supported by grants from the National Natural Science Foundation of China(81821002,81790251,81430071,81672381,81972665 and 81772487)Guangdong Basic and Applied Basic Research Foundation(2019B030302012)+1 种基金the National 973 Basic Research Program of China(2013CB911300)the Science and Technology Department of Sichuan Province(No.2017SZ0057,2019YJ0050).
文摘Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and xenobiotics.These effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions.Besides,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration disorder.In this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.
基金This work has been supported by the Liaoning Province Natural Science Foundation(Grant Nos.:2020-ZLLH-47,2020-MS-065,2021-YGJC-02,and 2017225054).Figures in the paper were drawn using Figdraw,and we sincerely thank the free drawing support provided by the Figdraw platform(www.fgdraw.com).We also would like to thank Editage(www.editage.cn)for English language editing.
文摘Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
文摘Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.
基金Supported by the National Project for Realization of 'Regenerative Medicine'Grants-in-Aid (14207046, 12557096) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technoloev, Japana erant from MITSUBISHI Foundation
文摘AIM： The treatment of liver disease is severely limited by a shortage of donor livers. In trying to address this growing problem, hepatocellular transplantation （HTx） has received much attention as an alternative to whole organ transplant. However, the expansion of transplanted cells is at low level, and the reconstitution of functional liver tissue is limited by this cellular property. We set up an animal model to better understand cell dose effect and the kinetics of liver repopulation following HTx. METHODS： Dipeptidyl peptidase Ⅳ （DPPⅣ）-deficient rats treated with retrorsine and subjected to partial hepatectomy were infused with DPPⅣ-positive hepatocytes. Rats were injected with varying numbers of donor hepatocytes down to 100 cells low, and liver repopulation was examined at different time points up to 20 mo long. Repopulation was assessed by computer-aided quantitative detection. RESULTS： Transplanted hepatocytes underwent multiple rounds of proliferation and stably repopulated the injured livers after 20 mo and at all cell doses. Transplanted cells divided 14 times within the 3-mo time period following infusion, and the liver repopulation reached a plateau between 3 and 20 too. Approximately 90% replacement occurred. Donor-derived cells also reconstituted the bile ductules of the recipients. CONCLUSION： The ability of transplanted hepatocytes to fully reconstitute injured livers strongly supports further investigation into the clinical potential of HTx. Additionally, the observation that transplanted hepatocytes also form components of the biliary system suggests that these cells may have bi-potential property of the stem cells.
基金supported by the Key Laboratory of Alzheimer’s Disease of Zhejiang Province(ZJAD-2021004)the National Natural Science Foundation of China(82201576)+2 种基金Beijing Hospitals Authority Youth Programme(QML20210804)Beijing Medical Research 2021-8(YZ)the National Natural Science Foundation of China(82150710557,82230043 and 82293642)to WS.
文摘Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune response.Each inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein ASC.Inflammasome formation typically occurs in response to infectious agents or cellular damage.The active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell death.Aberrant inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative disorders.As a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various diseases.Multiple clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting therapies.Therefore,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic strategies.In this article,we provide a summary of the biological and pathological roles of inflammasomes in health and disease.We also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.
文摘Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) have transformed diabetes management by targeting renal glucose reabsorption. Designed initially as antidiabetic agents, their ability to lower blood glucose levels independently of insulin is well-documented. Beyond glycemic control, emerging research has unveiled their profound cardiorenal benefits. By inhibiting SGLT-2 protein, these drugs enhance glucose excretion in urine, reducing blood glucose levels. This mechanism has translated into significant cardiovascular and renal protection, establishing SGLT-2 inhibitors as pivotal in managing not only diabetes but also cardiovascular and renal diseases. Recent studies have illuminated the broader therapeutic potential of SGLT-2 inhibitors beyond diabetes. Evidence indicates their efficacy in managing heart failure, chronic kidney disease (CKD), and cardiovascular complications in individuals with or without diabetes. This expanded therapeutic landscape has catalyzed a paradigm shift in SGLT-2 inhibitor use, positioning them as key agents in the cardiorenal metabolic continuum. Moreover, their role in the secondary prevention of cardiovascular events and slowing CKD progression in T2DM patients has garnered considerable attention. This consensus-based review aims to offer practical guidance in an algorithmic approach to primary care healthcare professionals to optimize SGLT-2 inhibitors utilization and maximize their benefits. The review seeks to empower clinicians to effectively manage patients who may benefit from SGLT-2 inhibitor therapy by addressing common initiation barriers and optimizing treatment strategies. Additionally, it aims to raise awareness among primary care physicians regarding the multifaceted benefits of these medications and overcome clinical inertia in their adoption into routine clinical practice.
文摘The aim of this review was to evaluate the therapeutic potential of exosomes, extracellular vesicles secreted by cells. They have emerged as potential therapeutic transporters for several diseases. This review provides an overview of exosomes’ therapeutic potential in cancer therapy and autoimmune conditions such as Coeliac Disease. The therapeutic effect is that the phospholipid-binding protein ANXA1 improves its anti-inflammatory properties. The review also analyzes the intricate processes of exosome production and composition ability to transport biomolecules such as proteins, microRNAs, and lipids, which promote intercellular communication and alter recipient cell behavior. Exosomes, linked to neurological disorders, cardiovascular disease, and cancer, present the means of targeted drug administration due to their innate specificity. Through genetic engineering and chemical modifications, exosomes can be tailored for specific purposes, demonstrating their versatility in targeted therapy. With ongoing research uncovering their therapeutic potential, exosomes present a promising frontier in novel medical treatments across various health conditions.
基金Supported by the Natural Science Foundation of Hebei Province,NO.H2018206307
文摘Exosomes are nanovesicles secreted from various types of cells and can be isolated from various bodily fluids, such as blood and urine. The number and molecular contents, including proteins and RNA of exosomes, have been shown to reflect their parental cell origins, characteristics and biological behaviors. An increasing number of studies have demonstrated that exosomes play a role in the course of tumorigenesis, diagnosis, treatment and prognosis, although its precise functions in tumors are still unclear. Moreover, owing to a lack of a standard approach, exosomes and its contents have not yet been put into clinical practice successfully. This review aims to summarize the current knowledge on exosomes and its contents in esophageal cancer as well as the current limitations/challenges in its clinical application, which may provide a basis for an all-around understanding of the implementation of exosomes and exosomal contents in the surveillance and therapy of esophageal cancer.
基金Supported by"Fondazione Cassa di Risparmio of Trieste"the"Fondazione Benefica Kathleen Foreman Casali of Trieste"+2 种基金the"Beneficentia Stiftung"of Vaduz Liechtensteinthe Italian Minister of Instruction,UniversityResearch(MIUR),PRIN 2010-11,No.20109PLMH2(in part)
文摘Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems.
基金by the National Natural Science Foundation of China[grant numbers 82170459,2021]Sichuan Science and Technology Program[grant numbers 2022YFH0007,2022]+2 种基金Sichuan Science and Technology Program[grant numbers 23NSFSC1345,2022]the Key Project of Application and Basic Research of Southwest Medical University[grant numbers 2021ZKZD016,2021]the Special Support Project for Young Talents of Southwest Medical University[grant numbers 2020-2022].
文摘In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.
基金supported by the National Natural Science Foundation of China(82230041,91949205,31730035,81721005)the National Key R&D Program of China(2016YFC1305800)the Guangdong Provincial Key S&T Program(018B030336001)。
文摘Abnormal hyperphosphorylation and accumulation of tau protein play a pivotal role in neurodegeneration in Alzheimer’s disease(AD)and many other tauopathies.Selective elimination of hyperphosphorylated tau is promising for the therapy of these diseases.We have conceptualized a strategy,named dephosphorylation-targeting chimeras(DEPTACs),for specifically hijacking phosphatases to tau to debilitate its hyperphosphorylation.Here,we conducted the step-by-step optimization of each constituent motif to generate DEPTACs with reasonable effectiveness in facilitating the dephosphorylation and subsequent clearance of pathological tau.Specifically,for one of the selected chimeras,D16,we demonstrated its significant efficiency in rescuing the neurodegeneration caused by neurotoxic K18-tau seeds in vitro.Moreover,intravenous administration of D16 also alleviated tau pathologies in the brain and improved memory deficits in AD mice.These results suggested DEPTACs as targeted modulators of tau phosphorylation,which hold therapeutic potential for AD and other tauopathies.
文摘Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and obesity.On the basis of the insights provided by Jiang et al,this editorial presents an exploration of the potential of mesenchymal stem cells(MSCs)for NAFLD treatment.MSCs have numerous desirable characteristics,including immunomodulation,anti-inflammatory pro-perties,and tissue regeneration promotion,rendering them attractive candidates for NAFLD treatment.Recent preclinical and early clinical studies have high-lighted the efficacy of MSCs in improving liver function and reducing disease severity in NAFLD models.However,MSC heterogeneity,long-term safety concerns,and unoptimized therapeutic protocols remain substantial challenges.Addressing these challenges through standardized protocols and rigorous clinical trials is essential to the safe and successful application of MSCs in NAFLD mana-gement.Continued research into MSC mechanisms and therapeutic optimization is required to improve treatments for NAFLD and related liver diseases.
