A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff ...A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.展开更多
Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the...Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.展开更多
Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on th...Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.展开更多
Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cyto...Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cytotoxic[using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphe nyl-2-H-tetrazolium bromide test],apoptotic(using a mitochondrial membrane potential assay),mutagenic(using a micronucleus test)and immunomodulatory(using flow cytometry)activities of the ethanolic extract of KG and its bioactive component,EPMC,against two cholangiocarcinoma(CCA)cell lines,CL-6 and HuCCT1,and one normal human cell line,OUMS-36 T-1 F.Results:Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells.The cytotoxic activity was supported by their concentration-dependent induction of apoptosis.CL-6 was most sensitive(3–4 fold)and selective to 5-fluorouracil(5-FU),compared with KG extract and EPMC[median half inhibiting concentration(IC50)and selectivity index(SI)were 23.01 lg/mL and 17.32;78.41 lg/mL and 4.44;100.76 lg/mL and 2.20,respectively for 5-FU vs.KG extract vs.EPMC].HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract[median IC50 and SI were 66.03 lg/mL and6.04;60.90 lg/mL and 3.65;156.60 lg/mL and 2.23,respectively for 5-FU vs.EPMC vs.KG extract].EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells(IC50=92.20 lg/mL).KG extract and EPMC exhibited concentration-dependent mutagenic activity,as well as inhibition of tumor necrosis factor-a and interleukin-6.Conclusion:Considering cytotoxic,apoptotic,immunomodulatory and mutagenic activities,further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.展开更多
The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular an...The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ^(+)cytotoxic CD8^(+)T cells in the spleen via induction of superoxide dismutase 3(SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases(JNK) and its downstream activator protein 1(AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA,through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases.展开更多
Objective:To establish immunomodulatory potential of aqueous extract of Polygonum minus(P.minus)leaves,the haematological effects and lysozyme activity of aqueous extract of P.minus leaf on Clarias gariepinus was stud...Objective:To establish immunomodulatory potential of aqueous extract of Polygonum minus(P.minus)leaves,the haematological effects and lysozyme activity of aqueous extract of P.minus leaf on Clarias gariepinus was studied.Methods:The fish were grouped and administered with the P.minus aqueous leaf extract intraperitoneally.Blood and serum samples were collected from each group and examined for various blood parameters.The turbidimetric assay for lysozyme activity using M.luteus and the survival rate of fish against A.hydrophila was carried out.Results:There was no significant impact(P>0.05)on white blood cell count,red blood cell count,mean corpuscular volume,mean corpuscular hemoglobin,mean corpuscular hemoglobin concentration and lysozyme activity was significantly(P<0.05)higher than control.The serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase levels were significantly lower than control(P<0.05).The highest dose group showed longest survival.Conclusions:From this study,it is considered that the aqueous extract of P.minus can be used as an immunostimulant in African catfish,but continuous administration may require maintaining the protection.展开更多
基金supported by the Open Project Program of Irradiation Preservation Technology Key Laboratory of Sichuan Province,Sichuan Institute of Atomic Energy(FZBC2020009)the Open Research Fund Program of Departmental and Municipal Co-construction of Crops Genetic Improvement of Hill Land Key Laboratory of Sichuan Province(2021CGIHL02)+2 种基金Science and Technology Support Project of Nanchong Science and Technology Bureau of Sichuan Province(20YFZJ0053 and 20YFZJ0054)the Sericulture Innovation Team of Sichuan Province(SCCXTD-2021-17)Laboratory of Sichuan Province(2021CGIHL02)。
文摘A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.
基金supported by grants from the Natural Science Foundation of China (81760778)the Fundamental Research Funds for Public-interest Scientific Institution in Xinjiang Uygur Autonomous Region (KYGY2016169)CAMS Innovation Fund for Medical Sciences (2017-I2M-1-012)
文摘Objective:To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa.Methods:The crude polysaccharide from roots of B.rapa(BRP)was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis.Results:Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity,including increasing production of nitric oxide(NO),tumor necrosis factor a(TNFa)and upregulating mRNA levels of inducible NO synthase(iNOS)and TNFa.Furthermore,modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B(NF-κB).Conclusion:The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.
基金support by the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research,China(Grant No.:2020YFE0205100)the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)+9 种基金the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)the National Natural Science Foundation of China(Grant Nos.:82141001,82274182,82074098,82173914)the China Academy of Chinese Medical Sciences(CACMS)Innovation Fund,China(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen,China(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen,China(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the National Key R&D Program of China Key Projects for International Cooperation on Science,Technology and Innovation(Grant No.:2020YFE0205100)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10),Shenzhen Governmental Sustainable Development Fund,China(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases,China(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties,China(Grant No.:SZGSP001).
文摘Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils’chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.
基金funded by Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma of Thammasat UniversityThammasat University Research fund under the TU Research Scholar(Contract No.03/2561)。
文摘Objective:To evaluate the cytotoxic,apoptotic,mutagenic and immunomodulatory activities of Kaempferia galanga Linn.(KG)extract and ethyl-p-methoxycinnamate(EPMC)in vitro.Methods:The present study investigated the cytotoxic[using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphe nyl-2-H-tetrazolium bromide test],apoptotic(using a mitochondrial membrane potential assay),mutagenic(using a micronucleus test)and immunomodulatory(using flow cytometry)activities of the ethanolic extract of KG and its bioactive component,EPMC,against two cholangiocarcinoma(CCA)cell lines,CL-6 and HuCCT1,and one normal human cell line,OUMS-36 T-1 F.Results:Both KG extract and EPMC exhibited moderate cytotoxic activity against both CCA cells.The cytotoxic activity was supported by their concentration-dependent induction of apoptosis.CL-6 was most sensitive(3–4 fold)and selective to 5-fluorouracil(5-FU),compared with KG extract and EPMC[median half inhibiting concentration(IC50)and selectivity index(SI)were 23.01 lg/mL and 17.32;78.41 lg/mL and 4.44;100.76 lg/mL and 2.20,respectively for 5-FU vs.KG extract vs.EPMC].HuCCT1 was relatively more sensitive and selective to 5-FU and EPMC than KG extract[median IC50 and SI were 66.03 lg/mL and6.04;60.90 lg/mL and 3.65;156.60 lg/mL and 2.23,respectively for 5-FU vs.EPMC vs.KG extract].EPMC produced relatively potent cytotoxic activity against polymorphonuclear cells(IC50=92.20 lg/mL).KG extract and EPMC exhibited concentration-dependent mutagenic activity,as well as inhibition of tumor necrosis factor-a and interleukin-6.Conclusion:Considering cytotoxic,apoptotic,immunomodulatory and mutagenic activities,further development of KG as a drug candidate is likely to focus on the oral pharmaceutical formulation of a standardized KG extract rather than isolated compounds.
基金supported by the National Natural Science Foundation of China (82030060)CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-042)。
文摘The immunomodulatory potential of dihydroartemisinin(DHA) has recently been highlighted;however, the potential mechanism remains to be clarified. Single-cell RNA sequencing was explored in combination with cellular and biochemical approaches to elucidate the immunomodulatory mechanisms of DHA. In this study, we found that DHA induced both spleen enlargement and rearrangement of splenic immune cell subsets in mice. It was revealed that DHA promoted the reversible expansion of effective regulatory T cells and interferon-γ^(+)cytotoxic CD8^(+)T cells in the spleen via induction of superoxide dismutase 3(SOD3) expression and increased phosphorylation of c-Jun N-terminal kinases(JNK) and its downstream activator protein 1(AP-1) transcription factors. Further, SOD3 knockout mice were resistant to the regulatory effect of DHA. Thus, DHA,through the activation of the SOD3-JNK-AP-1 axis, beneficially regulated immune cell heterogeneity and splenic immune cell homeostasis to treat autoimmune diseases.
文摘Objective:To establish immunomodulatory potential of aqueous extract of Polygonum minus(P.minus)leaves,the haematological effects and lysozyme activity of aqueous extract of P.minus leaf on Clarias gariepinus was studied.Methods:The fish were grouped and administered with the P.minus aqueous leaf extract intraperitoneally.Blood and serum samples were collected from each group and examined for various blood parameters.The turbidimetric assay for lysozyme activity using M.luteus and the survival rate of fish against A.hydrophila was carried out.Results:There was no significant impact(P>0.05)on white blood cell count,red blood cell count,mean corpuscular volume,mean corpuscular hemoglobin,mean corpuscular hemoglobin concentration and lysozyme activity was significantly(P<0.05)higher than control.The serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase levels were significantly lower than control(P<0.05).The highest dose group showed longest survival.Conclusions:From this study,it is considered that the aqueous extract of P.minus can be used as an immunostimulant in African catfish,but continuous administration may require maintaining the protection.