In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Amo...In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Among them, adenovirus-mediated genetransfection exhibits great advantages including highgene transfer efficiency and high expression level. Butthe optimal route of gene delivery is still uncertain.展开更多
An extract (G-INH) made from mature human granulocytes freshly isolated from normai blood causes human neutrophils to undergo apoptosis in vitro as shown by morphologic changes and by the typical ladder pattern of sma...An extract (G-INH) made from mature human granulocytes freshly isolated from normai blood causes human neutrophils to undergo apoptosis in vitro as shown by morphologic changes and by the typical ladder pattern of small DNA fragments noted on agarose gel electrophoresis of isolated DNA. Apoptosis occurs in from 20% to 30% of neutrophils over 24 hours of culture in vitro and the addition of G-INH to the medium causes a dose-related increase in the incidence of apoptosis. Heating G-INH at 60t for 30 minutes does not destroy its capacity to induce apoptosis but GM-CSF, G-CSF, and to a lesser extent IL-1β, antagonize this action. IL-3 does not diminish G-INH induced apoptosis of neutrophils. Substances, released from, mature neutrophils may participate in regulating the survival of other neutrophils, particularly in sites where the cells are in close proximity as in the marrow. Self destruction of post-mitotic neutrophils in marrow may thus represent an-other level at which regulation of cell production展开更多
OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decrease...OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.展开更多
Both rheumatoid arthritis and animal models ofautoimmune arthritis are characterized by hyper-activation of synovial cells and hyperplasia of the synovialmembrane. The activated synovial cells produceinflammatory cyto...Both rheumatoid arthritis and animal models ofautoimmune arthritis are characterized by hyper-activation of synovial cells and hyperplasia of the synovialmembrane. The activated synovial cells produceinflammatory cytokines and degradative enzymes whichlead to destruction of cartilage and bones. Effectivetreatment of arthritis may require elimination of most orall activated synovial cells. The death factor展开更多
Gene modification of tumor cells to express a varietyof cytokines such as IL-2 or the co-stimulatory moleculeB7. 1 led to increased immunogenicity and reducedtumorigenicity of tumors has several models and thisprocess...Gene modification of tumor cells to express a varietyof cytokines such as IL-2 or the co-stimulatory moleculeB7. 1 led to increased immunogenicity and reducedtumorigenicity of tumors has several models and thisprocess involves T cells. We have previously reporteddecreased tumorigenicity of the murine plasmacytomaJ558L (MHC class Ⅰ^+ and class Ⅱ^-) expressing IL-2 orB7. l. When systemic immunity was analyzed,展开更多
Background&Objective Tumor-associated macrophages(TAM)are induced by many cytokines,such as IL-4,IL-10,IL-13,and are considered to be of the M2 phenotype,which provides an immunosuppressive microenvironment for tu...Background&Objective Tumor-associated macrophages(TAM)are induced by many cytokines,such as IL-4,IL-10,IL-13,and are considered to be of the M2 phenotype,which provides an immunosuppressive microenvironment for tumor growth.However,biomechanistssuggest that cells in the tumor microenvironment are affected not only by chemical signals but also mechanical factors,of which the stiffness of tissues is a major determinant.Compared with normal tissues,including the peri-tumor tissues,tumor tissues are more rigid.Heretofore,the influence,on the differentiation and function of macrophages,of the differences in such physical aspect between展开更多
CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), i...CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), interleukin-6 (IL-6) and erythropoietin (EPO). The results revealed that: (D In methylcellulose culture, the plating efficiencies of purified cord blood CD34+ cells were much different when stimulated by various cytokines. IL-6 alone had the lowest colo-ny yield, while the combination of SCF, IL-6 and EPO had the highest yield. ② In the suspension culture, IL-6 alone or IL-6 + EPO had little expanding effect on cord blood CD34+ celis, the other cytokine combinations could expand cord blood CD34+ celis at different Ievels. Among them, the combination of SCF, IL-6 and EPO had the maximal expanding effect on cord blood CD34+ celis, the number of progenitor celis peaked at day 21, about 29-fold increase and nucleated celis increased approximately 3676-fold at day 28. The expanding effect of展开更多
Tumor microenvironment is composed of the tumor cells,stromal cells,microvascular tissue fluid,constitute small amount of infiltrating cells and cytokines.In recent years,more and more evidence that tumor microenviron...Tumor microenvironment is composed of the tumor cells,stromal cells,microvascular tissue fluid,constitute small amount of infiltrating cells and cytokines.In recent years,more and more evidence that tumor microenvironment play an important role in tumorigenesis.Tumor cells,immune cells and other mesenchymal cells interact and create an immunosuppressive microenvironment through a variety of immunosuppressive factors which vascular endothelial growth factor（VEGF）,transformed growth factor-β<sub>1</sub>（TGF-β<sub>1</sub>）and interleukin-10（IL-10）),which suppress immunology functions and promote tumor cells to escape immune surveillance,ultimately leading to tumor growth and metastasis.Dendritic cells（DCs）,the most potent antigen presenting cell as now known,play a key role in the anti-tumor immune process.The pre-展开更多
Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the...Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the tumor, which can’t activate immunosystemeffectively. Recent studies have shown that geneticallyengineered tumor cells expressing cytokines such as IL-2IFN-γ can induce greater CTL activity and activate NK,LAK and TIL. Besides IFN-γ can enhance the展开更多
OBJECTIVE Diosgenin(DG), a naturally occurring steroidal saponin, has been reported to offer a variety ofpharmacological activities including anti-diabetic and anti-tumor activity, anti-inflammatory and anti-AD. Howev...OBJECTIVE Diosgenin(DG), a naturally occurring steroidal saponin, has been reported to offer a variety ofpharmacological activities including anti-diabetic and anti-tumor activity, anti-inflammatory and anti-AD. However, the clinical application of DG is limited by its extremely low solubility and poor pharmacokinetic profile. In the present report,a novel diosgenin derivative with improved water-solubility was synthesized and its effect on the LPS-impaired hippocampal neurogenesis, cognition function and underlying mechanism was investigated. METHODS The effects of DG derivative on the adult hippocampal neurogenesis and cognition decline were investigated in a central LPS-induced inflammatory mice model, along with the fundamental mechanisms in vivo and in vitro using LPS-stimulated microglial BV2 cells. RESULTS DG derivative attenuates LPS-impaired neurogenesis by ameliorating the proliferation and differentiation of neural stem cells(NSCs), and prolonging their survival. The impaired neurogenesis in the hippocampal DG triggered the cognitive function, and that treatment of Arg-DG led to the recovery of cognitive decline. Arg-DG also suppressed the production of LPS-induced pro-inflammatory cytokines in hippocampal DG by blocking microglial activation. In in vitro study, Arg-DG inhibited the production of nitric oxide(NO), nitric oxide synthase(i NOS), cyclooxygenase-2(COX-2) expression, and prostaglandin D2 production(PGD2), as well as the pro-inflammatory cytokines, such as interleukin(IL)-6, IL-1β, and tumor necrosis factor alpha(TNF-α). The anti-inflammatory effect of Arg-DG was regulated by NF-κB and MAPK JNK signaling both in vivo, and in LPS-stimulated microglial BV2 cells. CONCLUSION These results suggest that Arg-DG might have the potential to treat the neurodegenerative disorders resulting from microgliamediated neuroinflammation.展开更多
OBJECTIVE It has been supposed that mast cells have important participation in the physiopathology of RA,however,the role of mast cells in the pathogenesis of RA remains unclear.In this study,we observed the antiapopt...OBJECTIVE It has been supposed that mast cells have important participation in the physiopathology of RA,however,the role of mast cells in the pathogenesis of RA remains unclear.In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts.METHODS Mast cells and fibroblasts synovial were obtained from mouse.Chemical mediator release was assessed by measuringβ-hexosa-minidase release.TSCS and bone marrow-derived mast cells were co-cultured;the toxic effects of TSCS on mast cell was measured by MTT and CCK-8 method;the releasing amount of tryptase in cell supernatants was measured by Elisa assay;the expression of FLS cell membrane receptor PAR-2 was detected by flow cytometry;the apoptosis of FLS cell was detected through flow cytometry and Western blotting;the level of activated Rho-GTP was detected by the pull-down method and Western blotting.RESULTS In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts,and found that tryptase significantly increased the expression of PAR-2 on the surface of fibroblast-like synovial cell,significantly activated Rho kinase,significantly inhibited apoptosis of fibroblast-like synovial cell induced by CH11.The release rates ofβ-hexosaminidase and the level of tryptase from bone marrow-derived mast cells after stimulation with different antigen and co-cultured with TSCS significantly decreased compared to the control group.In the co-culture system of mast cells and fibroblast-like synovial cells,TSCS treatment significantly inhibited Rho kinase(P<0.05),significantly promoted apoptosis of fibroblast-like synovial cell induced by CH11(P<0.05).CONCLUSION These results demonstrate that tryptase may play a key role in the physiopathology of RA.TSCS can inhibit mast cells activation and promote FLS cells apoptosis.This provide theoretical and experimental basis for the study of mast cells as targets for new anti-RA drugs.展开更多
OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand ...OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand white rabbits were randomly divided into six groups:normal control group,model group,dexamethasone group,Renqing Changjue high,middle and low dose group,with six rabbits in each group.LPS was used to replicate the ARDS model after five consecutive days of gavage.Arterial pressure,respiratory rate and anal temperature blood were recorded for arterial blood gas analysis at 0,0.5,1,2 and 4 h,respectively.At the end of the four-hour experiment,rabbits were killed by bloodletting,and the lung tissue was quickly removed to determine the cytokines,SOD,MDA and pathological examination of rabbit lung.RESULTS Renqing Changjue can significantly reduce the pathological changes of lung in ARDS model group.The expression of AQP1 and MPO in rabbit lung was significantly decreased by immunohistochemistry(P<0.05),reduce the lung wet/dry weight ratio,increase the ratio of PaO_(2)/FiO_(2),inhibit the release of inflammatory factors and scavenge free radicals and antioxidant effects.CONCLUSION Renqing Changjue can effectively protect rabbits with acute respiratory distress syndrome induced by LPS,and may protect the lung by inhibiting the release of cytokines and anti-oxidation.展开更多
OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of ...OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.展开更多
Cytokines provided locally at tbe tumor site mayinitiate an effective anti-tumor immune responsewhich leads to rejection of a tumor which otherwisegrows progressively. Experimentillly, this can betested by gene transf...Cytokines provided locally at tbe tumor site mayinitiate an effective anti-tumor immune responsewhich leads to rejection of a tumor which otherwisegrows progressively. Experimentillly, this can betested by gene transfer into cultured tumor cellsfollowed by the analysis of the tumorigenicity of suchgenetically engincered cells. This approach allows展开更多
Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leuko...Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leukocytosis(p-Leukocytosis) and paraneoplastic thrombocytosis(p-Thrombocytosis) in patients with non-small cell lung cancer(NSCLC). We also studied their relation to the expression of commonly detected molecular markers. Methods: We conducted a retrospective chart review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used to compare overall survival(OS) between patients with and without p-Leukocytosis(or) p-Thrombocytosis(p-Leuko/Thrombocytosis). Cox regression was used to determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC.Results: Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer survival compared patients with normal blood counts(P<0.001). In a multivariate survival analysis, both continued to correlate even when adjusted for histology, gender, stage and chemotherapy(P<0.01, 0.03 respectively). Stage I and II NSCLC with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC patients without paraneoplasia. Patients with the combined leukothrombocytosis syndrome did not have worse outcomes compared to those with either paraneoplastic syndrome alone. Conclusions: p-Leuko/Thrombocytosis is an accessible laboratory parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis portends poor survival. The role of various cytokines in tumor pathobiology provides a rationale for identifying cytokine factors responsible for the paraneoplasia and administering anti-cytokine therapies alongside traditional chemotherapy in an attempt to improve survival outcomes in these subset of patients.展开更多
文摘In recent years, great enthusiasm is given to theresearches of cancer gene therapy, which seems to bea promising novel strategy for cancer treatment.There are several strategies to deliver target genes intobodies. Among them, adenovirus-mediated genetransfection exhibits great advantages including highgene transfer efficiency and high expression level. Butthe optimal route of gene delivery is still uncertain.
基金Rothrock Research Fund in Hematology, The authors appreclate the assistance of supervising technicina, Linda Russ.Ulrica Stenheimer-Caudle, Sandra Peffly, and Marie Hyde.
文摘An extract (G-INH) made from mature human granulocytes freshly isolated from normai blood causes human neutrophils to undergo apoptosis in vitro as shown by morphologic changes and by the typical ladder pattern of small DNA fragments noted on agarose gel electrophoresis of isolated DNA. Apoptosis occurs in from 20% to 30% of neutrophils over 24 hours of culture in vitro and the addition of G-INH to the medium causes a dose-related increase in the incidence of apoptosis. Heating G-INH at 60t for 30 minutes does not destroy its capacity to induce apoptosis but GM-CSF, G-CSF, and to a lesser extent IL-1β, antagonize this action. IL-3 does not diminish G-INH induced apoptosis of neutrophils. Substances, released from, mature neutrophils may participate in regulating the survival of other neutrophils, particularly in sites where the cells are in close proximity as in the marrow. Self destruction of post-mitotic neutrophils in marrow may thus represent an-other level at which regulation of cell production
文摘OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis(UC),a recurrent and intractable inflammatory bowel disease.METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis,HLJ2 decreased weight loss,colon contracture,disease activity index(DAI),colon mucosa damage index(CMDI)and histopathological index(HI).HLJ2 also decreased myeloperoxidase(MPO)activity and reduced production of the inflammatory cytokines TNF-α,IL^(-1)β,and IL-6.HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate(DSS)and increased the expression of ZO-1 and claudin-1.Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2,including increased abundance of probiotics such as Lachnospiraceae,Prevotellaceae,and Lactobacillaceae.At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae,Porphyromonadaceae,Deferribacteraceae,and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice.CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation,regulates the intestinal flora,and protects the intestinal mucosa.It is thus a potential therapeutic agent for ulcerative colitis.
文摘Both rheumatoid arthritis and animal models ofautoimmune arthritis are characterized by hyper-activation of synovial cells and hyperplasia of the synovialmembrane. The activated synovial cells produceinflammatory cytokines and degradative enzymes whichlead to destruction of cartilage and bones. Effectivetreatment of arthritis may require elimination of most orall activated synovial cells. The death factor
文摘Gene modification of tumor cells to express a varietyof cytokines such as IL-2 or the co-stimulatory moleculeB7. 1 led to increased immunogenicity and reducedtumorigenicity of tumors has several models and thisprocess involves T cells. We have previously reporteddecreased tumorigenicity of the murine plasmacytomaJ558L (MHC class Ⅰ^+ and class Ⅱ^-) expressing IL-2 orB7. l. When systemic immunity was analyzed,
文摘Background&Objective Tumor-associated macrophages(TAM)are induced by many cytokines,such as IL-4,IL-10,IL-13,and are considered to be of the M2 phenotype,which provides an immunosuppressive microenvironment for tumor growth.However,biomechanistssuggest that cells in the tumor microenvironment are affected not only by chemical signals but also mechanical factors,of which the stiffness of tissues is a major determinant.Compared with normal tissues,including the peri-tumor tissues,tumor tissues are more rigid.Heretofore,the influence,on the differentiation and function of macrophages,of the differences in such physical aspect between
文摘CD34+ cells from human umbilical cord blood were purified by Dynal beads M-450 CD34 immunoselection system and cultured in the presence of various cytokines alone or in combination, including stem cell factor (SCF), interleukin-6 (IL-6) and erythropoietin (EPO). The results revealed that: (D In methylcellulose culture, the plating efficiencies of purified cord blood CD34+ cells were much different when stimulated by various cytokines. IL-6 alone had the lowest colo-ny yield, while the combination of SCF, IL-6 and EPO had the highest yield. ② In the suspension culture, IL-6 alone or IL-6 + EPO had little expanding effect on cord blood CD34+ celis, the other cytokine combinations could expand cord blood CD34+ celis at different Ievels. Among them, the combination of SCF, IL-6 and EPO had the maximal expanding effect on cord blood CD34+ celis, the number of progenitor celis peaked at day 21, about 29-fold increase and nucleated celis increased approximately 3676-fold at day 28. The expanding effect of
文摘Tumor microenvironment is composed of the tumor cells,stromal cells,microvascular tissue fluid,constitute small amount of infiltrating cells and cytokines.In recent years,more and more evidence that tumor microenvironment play an important role in tumorigenesis.Tumor cells,immune cells and other mesenchymal cells interact and create an immunosuppressive microenvironment through a variety of immunosuppressive factors which vascular endothelial growth factor（VEGF）,transformed growth factor-β<sub>1</sub>（TGF-β<sub>1</sub>）and interleukin-10（IL-10）),which suppress immunology functions and promote tumor cells to escape immune surveillance,ultimately leading to tumor growth and metastasis.Dendritic cells（DCs）,the most potent antigen presenting cell as now known,play a key role in the anti-tumor immune process.The pre-
文摘Tumor cells may escape immune surveillance mainlyby (1) down regulation of major histocompatibilitycomplex (MHC) molecules or alteration of antigen-processing pathways; (2) low-level of cytokines in thevicinity of the tumor, which can’t activate immunosystemeffectively. Recent studies have shown that geneticallyengineered tumor cells expressing cytokines such as IL-2IFN-γ can induce greater CTL activity and activate NK,LAK and TIL. Besides IFN-γ can enhance the
文摘OBJECTIVE Diosgenin(DG), a naturally occurring steroidal saponin, has been reported to offer a variety ofpharmacological activities including anti-diabetic and anti-tumor activity, anti-inflammatory and anti-AD. However, the clinical application of DG is limited by its extremely low solubility and poor pharmacokinetic profile. In the present report,a novel diosgenin derivative with improved water-solubility was synthesized and its effect on the LPS-impaired hippocampal neurogenesis, cognition function and underlying mechanism was investigated. METHODS The effects of DG derivative on the adult hippocampal neurogenesis and cognition decline were investigated in a central LPS-induced inflammatory mice model, along with the fundamental mechanisms in vivo and in vitro using LPS-stimulated microglial BV2 cells. RESULTS DG derivative attenuates LPS-impaired neurogenesis by ameliorating the proliferation and differentiation of neural stem cells(NSCs), and prolonging their survival. The impaired neurogenesis in the hippocampal DG triggered the cognitive function, and that treatment of Arg-DG led to the recovery of cognitive decline. Arg-DG also suppressed the production of LPS-induced pro-inflammatory cytokines in hippocampal DG by blocking microglial activation. In in vitro study, Arg-DG inhibited the production of nitric oxide(NO), nitric oxide synthase(i NOS), cyclooxygenase-2(COX-2) expression, and prostaglandin D2 production(PGD2), as well as the pro-inflammatory cytokines, such as interleukin(IL)-6, IL-1β, and tumor necrosis factor alpha(TNF-α). The anti-inflammatory effect of Arg-DG was regulated by NF-κB and MAPK JNK signaling both in vivo, and in LPS-stimulated microglial BV2 cells. CONCLUSION These results suggest that Arg-DG might have the potential to treat the neurodegenerative disorders resulting from microgliamediated neuroinflammation.
基金The project supported by National Natural Science Foundation of China(81274166,81673665)Project in Hubei Province Department of Education(B20101201)+1 种基金Yichang City Technology Bureau Project(2010A01301-04)China Three Gorges University Research Fund(0620080702)
文摘OBJECTIVE It has been supposed that mast cells have important participation in the physiopathology of RA,however,the role of mast cells in the pathogenesis of RA remains unclear.In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts.METHODS Mast cells and fibroblasts synovial were obtained from mouse.Chemical mediator release was assessed by measuringβ-hexosa-minidase release.TSCS and bone marrow-derived mast cells were co-cultured;the toxic effects of TSCS on mast cell was measured by MTT and CCK-8 method;the releasing amount of tryptase in cell supernatants was measured by Elisa assay;the expression of FLS cell membrane receptor PAR-2 was detected by flow cytometry;the apoptosis of FLS cell was detected through flow cytometry and Western blotting;the level of activated Rho-GTP was detected by the pull-down method and Western blotting.RESULTS In this study,we observed the antiapoptotic effects of tryptase released by mast cell on RA synovial fibroblasts,and found that tryptase significantly increased the expression of PAR-2 on the surface of fibroblast-like synovial cell,significantly activated Rho kinase,significantly inhibited apoptosis of fibroblast-like synovial cell induced by CH11.The release rates ofβ-hexosaminidase and the level of tryptase from bone marrow-derived mast cells after stimulation with different antigen and co-cultured with TSCS significantly decreased compared to the control group.In the co-culture system of mast cells and fibroblast-like synovial cells,TSCS treatment significantly inhibited Rho kinase(P<0.05),significantly promoted apoptosis of fibroblast-like synovial cell induced by CH11(P<0.05).CONCLUSION These results demonstrate that tryptase may play a key role in the physiopathology of RA.TSCS can inhibit mast cells activation and promote FLS cells apoptosis.This provide theoretical and experimental basis for the study of mast cells as targets for new anti-RA drugs.
基金2020 Project of Tibetan Medicine Administration of Tibet Autonomous Region(JJKT202004)and 2020 Reform and Development Special Project(324042000101)。
文摘OBJECTIVE To investigate whether Renqing Changjue has a protective effect on acute respiratory distress syndrome(ARDS)induced by endotoxin lipopolysaccharide(LPS)in rabbits.METHODS Thirty-six healthy male New Zealand white rabbits were randomly divided into six groups:normal control group,model group,dexamethasone group,Renqing Changjue high,middle and low dose group,with six rabbits in each group.LPS was used to replicate the ARDS model after five consecutive days of gavage.Arterial pressure,respiratory rate and anal temperature blood were recorded for arterial blood gas analysis at 0,0.5,1,2 and 4 h,respectively.At the end of the four-hour experiment,rabbits were killed by bloodletting,and the lung tissue was quickly removed to determine the cytokines,SOD,MDA and pathological examination of rabbit lung.RESULTS Renqing Changjue can significantly reduce the pathological changes of lung in ARDS model group.The expression of AQP1 and MPO in rabbit lung was significantly decreased by immunohistochemistry(P<0.05),reduce the lung wet/dry weight ratio,increase the ratio of PaO_(2)/FiO_(2),inhibit the release of inflammatory factors and scavenge free radicals and antioxidant effects.CONCLUSION Renqing Changjue can effectively protect rabbits with acute respiratory distress syndrome induced by LPS,and may protect the lung by inhibiting the release of cytokines and anti-oxidation.
基金China Pharmaceutical University "Double First-Class" University project(CPU2018GY32)National Science and Technology Major Project of China(2016ZX09101031)
文摘OBJECTIVE Psoriasis is an immune system meditated disease,especially T cells.It disturbed many people around the world and hard to therapy.Paeonia lactiflora Pall has been used as a medicine in china for thousands of years.Recent studies has found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases.In this study,we researched the effects and possible mechanisms of total glucosides of paeony(TGP)on animal psoriasis in order to study the therapeutic effects and mechanisms of TGP in 5%propranolol creaminduced psoriasis in guinea pigs and Imiquimod(IMQ)cream-induced psoriasis in mice.METHODS The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice.Ear thickness was accessed,and pathology injury was observed by HE staining.The levels of serum IL-1β,IL-6,IL-12,IL-17,IL-23,TNF-α,and IFN-γ,skin IL-17A,IL-22 and orphan nuclear receptor(RORγt)mRNA expression,proliferating cell nuclear antigen(PCNA),total or phosphorylated signal transducers and activators of transcription(STAT1 and STAT3)were determined by ELISA,real time PCR,immu⁃nohistochemical staining,and Western blotting,respectively.RESULTS Compared with model group,TGP treatment decreased the ear thickness,improved pathology of psoriasis,alleviated IMQ-induced keratinocyte proliferation,reduced the inflammatory cytokine,and downregulated IL-17A,IL-22,and RORγt mRNA in mice.Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.CONCLUSION TGP alleviates the symptoms of psoriasis-like guinea pigs and mice,and the possible mechanism may relate to inhibit T helper 17(TH17)cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.
文摘Cytokines provided locally at tbe tumor site mayinitiate an effective anti-tumor immune responsewhich leads to rejection of a tumor which otherwisegrows progressively. Experimentillly, this can betested by gene transfer into cultured tumor cellsfollowed by the analysis of the tumorigenicity of suchgenetically engincered cells. This approach allows
文摘Background and Objectives: Search for inexpensive laboratory markers have identified associations between blood counts and lung cancer outcomes. In this study, we evaluated the prognostic value of paraneoplastic leukocytosis(p-Leukocytosis) and paraneoplastic thrombocytosis(p-Thrombocytosis) in patients with non-small cell lung cancer(NSCLC). We also studied their relation to the expression of commonly detected molecular markers. Methods: We conducted a retrospective chart review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used to compare overall survival(OS) between patients with and without p-Leukocytosis(or) p-Thrombocytosis(p-Leuko/Thrombocytosis). Cox regression was used to determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC.Results: Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer survival compared patients with normal blood counts(P<0.001). In a multivariate survival analysis, both continued to correlate even when adjusted for histology, gender, stage and chemotherapy(P<0.01, 0.03 respectively). Stage I and II NSCLC with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC patients without paraneoplasia. Patients with the combined leukothrombocytosis syndrome did not have worse outcomes compared to those with either paraneoplastic syndrome alone. Conclusions: p-Leuko/Thrombocytosis is an accessible laboratory parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis portends poor survival. The role of various cytokines in tumor pathobiology provides a rationale for identifying cytokine factors responsible for the paraneoplasia and administering anti-cytokine therapies alongside traditional chemotherapy in an attempt to improve survival outcomes in these subset of patients.
