Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the im...The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the immunomodulatory effects have been paid more and more attention by scholars,but there was no systematic introduction of their immunomodulatory mechanism.So,this review introduced the immunomodulatory effects and mechanism of edible fungus polysaccharides in recent years,and then the relationships between structure and immunomodulatory effect were also discussed.展开更多
Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the f...Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the first time.In addition,the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium(MTS)assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro.Moreover,flazin(20μg·mL^(−1))altered the populations of splenic lymphocyte subtypes.Real-time quantitative PCR(RT-qPCR)analysis and enzyme-linked immunosorbent assay(ELISA)showed that flazin suppressed the mRNA expression and secretion of TNF-αand IL-2,and reversed Concanavalin A(ConA)-induced mRNA up-regulation and protein secretion of TNF-αand IL-2.Western blot results showed that flazin reversed ConA-induced increases in p-ERK1/2 and p-p38 in splenocytes.In conclusion,flazin exhibits effective immunomodulatory function and may be useful for treating immune-related disorders,which indicates the application potential of C.sikamea as a functional food or immunomodulator.展开更多
TW19 is a diterpene compound isolated from the root cortex of Tripterygium Wil- fordii Hood. F.. Its effects on the immune function in ICR mice and the male fertility in SD rats, ICR mice and Kunming mice were eva...TW19 is a diterpene compound isolated from the root cortex of Tripterygium Wil- fordii Hood. F.. Its effects on the immune function in ICR mice and the male fertility in SD rats, ICR mice and Kunming mice were evaluated. TW19 was given orally for 5 weeks. Then the antifertilitic effect was assessed by mating test. The results showed that ED50, for anti-fertilitic were 332μg/kg, 369. 9μg/kg and 286. 8 μg/kg per day in SD rats, ICR mice and Kunming mice respectively. After the treatment of TW19 at antifertility dose for 5 weeks consecutively, the spermatozoa density and motility of trial animals reduced significantly, The weight of testic also declined in SD rats and Kunming mice, but no effects were observed in ICR mice. TW19 inhibited prolifera- tion of splenic T and B-lymphocytes of ICR mice in vitro and hence inhibited the anti- body formation in vivo, but compared with T 4, the immunosuppressive effect of TW19 was less obvious.展开更多
Liver failure is a critical and life-threatening condition in hepatology,challenging management,limited therapeutic options,and generally poor prognosis.For the treatment of liver failure,mesenchymal stem cells(MSCs)a...Liver failure is a critical and life-threatening condition in hepatology,challenging management,limited therapeutic options,and generally poor prognosis.For the treatment of liver failure,mesenchymal stem cells(MSCs)and mesenchymal stem cell-derived extracellular vesicles(MSCs-EVs)offer promising prospects.This article provides an overview and immunological characteristics of MSCs and MSCs-EVs,explains the immunological imbalance in liver failure,details the immunological mechanisms of MSCs and MSCs-EVs in treating liver failure,and discusses their potential application and key issues.It aims to provide valuable insight for basic research and clinical application of MSCs/MSCs-EVs in liver failure.展开更多
Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational a...Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational antibiotic use contributes to the development of resistance in bacteria and antibiotic residues in animal products,threatening public health,while causing gut microbiota dysbiosis and antibiotic-resistant bacterial infection in piglets.Therefore,the quest for alternative products(such as probiotics,prebiotics,organic acids,enzymes;essential oils,medium-chain fatty acids,zinc,and plant extracts)has recently been clearly emphasized through the increase in regulations regarding antibiotic use in livestock production.These antibiotic alternatives could lower the risk of antibiotic-resistant bacteria and meet consumer demand for antibiotic-free food.Several antibiotic alternatives have been proposed,including immunomodulatory probiotics,as candidates to reduce the need for antimicrobial therapy.Many studies have revealed that probiotics can avert and cure bacterial diarrhea by regulating the gut function and immune system of piglets.In this review,we focus on the major pathogenic bacteria causing piglet diarrhear the research sta of using probiotics to prevent and treat diarrhea,their possible mechanisms,and the safety issues related to the use of probiotics.Supplementation with probiotics is a possible alternative to antibiotics for the prevention or treatment of bacterial diarrhea in piglets.Furthermore,probiotics exe rt beneficial effects on feed efficiency and growth performance of piglets.Therefore,appropriate selection and strategies for the use of probiotics may have a positive effect on growth performance and also reduce diarrhea in piglets.This review provides useful information on probiotics for researchers,pig nutritionists,and the additive industry to support their use against bacterial,diarrhea in piglets.展开更多
Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal ste...Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining.The expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting.PBMCs,hAMSCs,and their exosomes were collected for in vitro group culture.Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent assay.Results:The hAMSCs and exosomes were successfully extracted from the human amniotic membrane.TGF-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in hAMSCs.In vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than exosomes.Conclusions:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.展开更多
Background: Mesenchymal stromal cells (MSC) are being tested for the treatment of immune diseases. MSC are present in several adult tissues which milieu may influence MSC behavior particularly under inflammatory condi...Background: Mesenchymal stromal cells (MSC) are being tested for the treatment of immune diseases. MSC are present in several adult tissues which milieu may influence MSC behavior particularly under inflammatory conditions. Additionally, culture conditions also can modify cell function or state of activation. Methods: To address the influence of the MSC source on its characteristics, we studied a xenofree, platelet lysate supplemented MSC from dental pulp, adipose tissue and bone marrow, co-cultured with isolated T cells and PBMC subset, and studied the effect of culture animal or human supplements immunomodulatory effect. Results: All three sources were efficient in inhibiting T cells. Among all MSC sources, as also described by others, adipose MSC was capable to significantly induce Treg phenotype and decrease T CD8+. Furthermore, comparing fetal bovine serum and platelet lysate, results demonstrate that platelet lysate alone is capable to induce immunomodulatory phenotype. Additional studies have to be made to elucidate the PL immunomodulatory effect.展开更多
The comprehensive recognition of communications between bone marrow mesenchymal stem cells(bm-MSCs)and macrophages in the peri-implant microenvironment is crucial for implantation prognosis.Our previous studies have c...The comprehensive recognition of communications between bone marrow mesenchymal stem cells(bm-MSCs)and macrophages in the peri-implant microenvironment is crucial for implantation prognosis.Our previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage polarization.However,cell communication is commutative and multi-directional.As the immune regulatory properties of MSCs have become increasingly prominent,whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is unclear.To further illuminate the communications between bm-MSCs and macrophages,the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages,and by blocking exosome secretion or extracting the purified exosomes to induce independently,we bidirectionally confirmed that under the influence of TiO_(2)nanoporous topography with 80-100 nm tube diameters,bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages,adversely affecting the osteogenic microenvironment around the implant.This finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.展开更多
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
基金This research was financially supported by Major Public Welfare Projects in Henan Province(201300110200)National Key R&D Program of China(2018YFD0400200)+2 种基金Key scientific and technological key projects of Henan science and Technology Department(192102110214 and 202102110283)Henan Province Industry-University-Research Cooperation Project(182107000033)the special fund project of Zhengzhou basic and applied basic research(ZZSZX202003).
文摘The polysaccharides from edible fungus showed many kinds of biological activities,including anti-tumor,immunomodulatory,anti-inflammatory,anti-diabetes,improving functional constipation activities.In particular,the immunomodulatory effects have been paid more and more attention by scholars,but there was no systematic introduction of their immunomodulatory mechanism.So,this review introduced the immunomodulatory effects and mechanism of edible fungus polysaccharides in recent years,and then the relationships between structure and immunomodulatory effect were also discussed.
基金Education Department of Jilin Province(No.JJKH20201177KJ)the Foundation of Department of Human Resources and Social Security of Jilin Province(No.2020009)the Foundation of Jilin Province Development and Reform Commission(No.2020C015).
文摘Crassostrea sikamea(C.sikamea)is an important edible and medicinal seafood in China.In the present study,a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea(EAECs)for the first time.In addition,the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium(MTS)assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro.Moreover,flazin(20μg·mL^(−1))altered the populations of splenic lymphocyte subtypes.Real-time quantitative PCR(RT-qPCR)analysis and enzyme-linked immunosorbent assay(ELISA)showed that flazin suppressed the mRNA expression and secretion of TNF-αand IL-2,and reversed Concanavalin A(ConA)-induced mRNA up-regulation and protein secretion of TNF-αand IL-2.Western blot results showed that flazin reversed ConA-induced increases in p-ERK1/2 and p-p38 in splenocytes.In conclusion,flazin exhibits effective immunomodulatory function and may be useful for treating immune-related disorders,which indicates the application potential of C.sikamea as a functional food or immunomodulator.
文摘TW19 is a diterpene compound isolated from the root cortex of Tripterygium Wil- fordii Hood. F.. Its effects on the immune function in ICR mice and the male fertility in SD rats, ICR mice and Kunming mice were evaluated. TW19 was given orally for 5 weeks. Then the antifertilitic effect was assessed by mating test. The results showed that ED50, for anti-fertilitic were 332μg/kg, 369. 9μg/kg and 286. 8 μg/kg per day in SD rats, ICR mice and Kunming mice respectively. After the treatment of TW19 at antifertility dose for 5 weeks consecutively, the spermatozoa density and motility of trial animals reduced significantly, The weight of testic also declined in SD rats and Kunming mice, but no effects were observed in ICR mice. TW19 inhibited prolifera- tion of splenic T and B-lymphocytes of ICR mice in vitro and hence inhibited the anti- body formation in vivo, but compared with T 4, the immunosuppressive effect of TW19 was less obvious.
基金funded by Shanxi Key Research and Development Program(201903D421056).
文摘Liver failure is a critical and life-threatening condition in hepatology,challenging management,limited therapeutic options,and generally poor prognosis.For the treatment of liver failure,mesenchymal stem cells(MSCs)and mesenchymal stem cell-derived extracellular vesicles(MSCs-EVs)offer promising prospects.This article provides an overview and immunological characteristics of MSCs and MSCs-EVs,explains the immunological imbalance in liver failure,details the immunological mechanisms of MSCs and MSCs-EVs in treating liver failure,and discusses their potential application and key issues.It aims to provide valuable insight for basic research and clinical application of MSCs/MSCs-EVs in liver failure.
基金supported by Grants-in-Aid for Scientific Research(A)(19H00965,23H00354 HK)Grant-in-Aid for Scientific Research(B)(23H02358,KN)+4 种基金Grant-in-Aid for Research Activity Start-up(23K19327,FN)Challenging Research(Exploratory,23K18072,HK)JSPS Fellows(22F22080,HK)from the Japan Society for the Promotion of Science(JSPS)supported by the Research Program on Development of Innovative Technology Grants(JPJ007097)from the Project of the Bio-Oriented Technology Research Advancement Institution(BRAIN)and by the Japan Racing Association to HKsupported by the JSPS Core-to-Core Program,A.Advanced Research Networks,titled Establishment of the International Agricultural Immunology Research Core for Quantum Improvement in Food Safety。
文摘Diarrhea is a common enteric disease in piglets that leads to high mortality and economic losses in swine production worldwide.Antibiotics are commonly used to prevent or treat diarrhea in piglets.However,irrational antibiotic use contributes to the development of resistance in bacteria and antibiotic residues in animal products,threatening public health,while causing gut microbiota dysbiosis and antibiotic-resistant bacterial infection in piglets.Therefore,the quest for alternative products(such as probiotics,prebiotics,organic acids,enzymes;essential oils,medium-chain fatty acids,zinc,and plant extracts)has recently been clearly emphasized through the increase in regulations regarding antibiotic use in livestock production.These antibiotic alternatives could lower the risk of antibiotic-resistant bacteria and meet consumer demand for antibiotic-free food.Several antibiotic alternatives have been proposed,including immunomodulatory probiotics,as candidates to reduce the need for antimicrobial therapy.Many studies have revealed that probiotics can avert and cure bacterial diarrhea by regulating the gut function and immune system of piglets.In this review,we focus on the major pathogenic bacteria causing piglet diarrhear the research sta of using probiotics to prevent and treat diarrhea,their possible mechanisms,and the safety issues related to the use of probiotics.Supplementation with probiotics is a possible alternative to antibiotics for the prevention or treatment of bacterial diarrhea in piglets.Furthermore,probiotics exe rt beneficial effects on feed efficiency and growth performance of piglets.Therefore,appropriate selection and strategies for the use of probiotics may have a positive effect on growth performance and also reduce diarrhea in piglets.This review provides useful information on probiotics for researchers,pig nutritionists,and the additive industry to support their use against bacterial,diarrhea in piglets.
基金Research Program of Health Committee of Hunan Province(202106010870)to Xin Tian.
文摘Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining.The expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting.PBMCs,hAMSCs,and their exosomes were collected for in vitro group culture.Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent assay.Results:The hAMSCs and exosomes were successfully extracted from the human amniotic membrane.TGF-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in hAMSCs.In vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than exosomes.Conclusions:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.
文摘Background: Mesenchymal stromal cells (MSC) are being tested for the treatment of immune diseases. MSC are present in several adult tissues which milieu may influence MSC behavior particularly under inflammatory conditions. Additionally, culture conditions also can modify cell function or state of activation. Methods: To address the influence of the MSC source on its characteristics, we studied a xenofree, platelet lysate supplemented MSC from dental pulp, adipose tissue and bone marrow, co-cultured with isolated T cells and PBMC subset, and studied the effect of culture animal or human supplements immunomodulatory effect. Results: All three sources were efficient in inhibiting T cells. Among all MSC sources, as also described by others, adipose MSC was capable to significantly induce Treg phenotype and decrease T CD8+. Furthermore, comparing fetal bovine serum and platelet lysate, results demonstrate that platelet lysate alone is capable to induce immunomodulatory phenotype. Additional studies have to be made to elucidate the PL immunomodulatory effect.
基金supported by the National Natural Science Foundation of China(grant numbers 82101064,81971752)the Basic Natural Science Research Program of Shaanxi Province(grant number 2021JQ-424)Xi’an Jiaotong University school-level project(grant number xjh012020012).
文摘The comprehensive recognition of communications between bone marrow mesenchymal stem cells(bm-MSCs)and macrophages in the peri-implant microenvironment is crucial for implantation prognosis.Our previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage polarization.However,cell communication is commutative and multi-directional.As the immune regulatory properties of MSCs have become increasingly prominent,whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is unclear.To further illuminate the communications between bm-MSCs and macrophages,the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages,and by blocking exosome secretion or extracting the purified exosomes to induce independently,we bidirectionally confirmed that under the influence of TiO_(2)nanoporous topography with 80-100 nm tube diameters,bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages,adversely affecting the osteogenic microenvironment around the implant.This finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.
