The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ...The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.展开更多
AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of r...AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of rats was established by retrograde injection of 5% sodium taurocholate （1 mL/kg） into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators： decay accelerating factor （DAF; CD55）, 20 ku homologous restriction factor （HRF20; CD59） and membrane cofactor protein （MCP; CEH6）, in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A （n = 21） received no treatment after the SAP model was established; group B （n = 20） was given IL-4 （8 IJg/animal） intraperitoneally 0.5 h before the SAP model was established; group C （n = 20） was given IL-4 （8 μg/animal） intraperitoneaUy 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS： Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis （r = -0.748, -0.827, -0.723; P〈0.01）. In the second series of experiments, no matter when the treatment of IL-4 was given （before or after the induction of SAP model）, the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model （P〈0.01, P〈0.05）, but the expression of MCP was not influenced （P〉0.05）. The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model （P〈0.05）, but the expression of CD59 and MCP did not change （P〉0.05）. CONCLUSION： Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.展开更多
A plant fermentation was carried out by Lactobaccilli against the Rhizome from Pueraria milifica (f-PMF). This material was evidenced by safe in animal toxic study. The main aim of this study was to revise the traditi...A plant fermentation was carried out by Lactobaccilli against the Rhizome from Pueraria milifica (f-PMF). This material was evidenced by safe in animal toxic study. The main aim of this study was to revise the traditional way of hot water extraction to fermentation so as to use up the original material and finding new activity. We tried to show the new activity through phytoestrogen and immune-competent cells from the host that administrated either of original remedy and the new fermented sample, plus activated water SRE. In mice, compromised host was prepared by cancer chemotherapeutic agent (Mitomycin-C). After administration of f-PMF to immno-suppressed animals, the effects by both samples were augmented by lymphocyte in number and functions, macrophage activities, anti-oxidative activity. However, the intense of effect was much more by fermented one but not by conventional one. The anti-oxidative assay was also carried out ex-vivo system by peritoneal macrophage that we proposed as suitable system for evaluating anti-oxidative assay. In our clinical study by 20 healthy volunteers, granulocyte and lymphocyte ratio was regulated as neutral in peripheral white blood cells, increasing one, two and three weeks after the administration of f-PMF. We have found the significant regulation of blood chemical factors that were important makers for the lifestyle-related diseases. The mechanism of augmentation by probing directory with immuno-electrophoretic method, generating new complement component, especially found by alternative pathway of complement. So we discussed the process concerning designed f-PMF molecule for activation of complement component and bound for the biological activity of each physical component. In a limited condition, fewer numbers of volunteers, the breast size was tending to increase along with the administration time. Including these evidences, we discussed the possibility of this traditional ethnic medicine, originally found and spread in the highland area in Thailand and Myanmar.展开更多
Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as ...Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.展开更多
BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury re...BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.AIM To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.METHODS A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment.We detected the effects of C2-FH on liver function,inflammatory response and complement activation.Additionally,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.RESULTS C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by APAP.Moreover,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury.RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.CONCLUSION C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.展开更多
Objective: To study the mechanism of T-cell activation induced by non-lethal complement attack and the role of CD59 in this process. Methods: Human CD59 and its transmentbrane counterpart CD59TM cDNA were transfected ...Objective: To study the mechanism of T-cell activation induced by non-lethal complement attack and the role of CD59 in this process. Methods: Human CD59 and its transmentbrane counterpart CD59TM cDNA were transfected into murine thymoma EL-4 cells. Activation and proliferation of EL-4 transfectants were observed with MIT assay. Results:Both CD59 and CD59 TM cDNA expressed on EL-4 cells effectively inhibited complement-mediated membrane damage. Cross-linking of CD59 with antibody induced activation of CD59/EL-4 cells but not CDS9TM/EL-4 cells. This effect was inhibited by Herbimycin A. a special protein tyrosine kinase (PTK) inhibitor. Non-lethal complement attack induced CD59/EL-4 but not CD59TMIEL-4 cell to proliferate, and this reaction was not blocked by Herbimycin A. Conclusion: CD59 takes part in T cell activation induced by non-lethal complement attack. The mechanisms of T cell activation induced by non-lethal complement attack arc different from those by cross-linking of CD59.展开更多
In this study,polysaccharides were extracted from blueberry fruit(BFP)and isolated to 3 components(BFP-1,BFP-2 and BFP-3).The molecular weight,monosaccharide composition,characteristic groups,microscopic morphology,an...In this study,polysaccharides were extracted from blueberry fruit(BFP)and isolated to 3 components(BFP-1,BFP-2 and BFP-3).The molecular weight,monosaccharide composition,characteristic groups,microscopic morphology,and triple helical conformation of the polysaccharides were characterized using high performance permeation chromatography,high performance liquid chromatography,gas chromatographymass spectrometry,Fourier transform infrared spectrometer,scanning electron microscope and Congo red staining.Moreover,the hypolipidemic and immunological activities of the polysaccharides were also assessed.Results showed that the molecular weights of polysaccharides BFP-1,BFP-2,and BFP-3 were 5.547×10^(4),5.671×10^(4),and 3.951×10^(4)Da,respectively,the main monosaccharides were glucose(Glc),galactose(Gal)and arabinose(Ara),but BFP-3 was mainly composed of galacturonic acid(Gal A),Glc,Gal,and Ara.The backbone of BFP-1 was→4)-Glcp-(1→,which branches to Ara and xylose(Xyl)residues,while the backbone of BFP-2 was→5)-Araf-(1→,which branches to Xyl,Glc,rhamnose(Rha)and Gal residues,in particularly,BFP-3 has a more complex branching with a→3,6)-Galp-(1→)backbone,the side chain is dominated by Araf-(1→).Blueberry polysaccharides are pyran-type polysaccharides withα-glycosidic bonds,and BFP-1 has a typical triple-helical structure.The activity assay revealed that the binding of BFP-3 to sodium glycylcholate hydrate and sodium taurocholate was 79.95%and 78.50%,respectively,indicating that it had better hypolipidemic activity than the others.Immunoactivity assay showed that BFP promoted NO secretion through activating the NF-κB signalling pathway in RAW264.7 cells,which played a role in enhancing the immune function of the organism.These findings may provide a reference for the development and application of blueberry polysaccharides in functional food and medicine.展开更多
in order to verify whether the bactericidal capacity of polymorphonuclear neutrophils (PMNs)could be abolished by the bypass-activated complement,intracellular bactericidal activity (ICBA),superoxide ions (O2-) and sp...in order to verify whether the bactericidal capacity of polymorphonuclear neutrophils (PMNs)could be abolished by the bypass-activated complement,intracellular bactericidal activity (ICBA),superoxide ions (O2-) and specific granules (SGs) 3 were determine展开更多
AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was i...AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.展开更多
Oyster,as a common aquatic food,play an important role in shellfish allergy.In this study,2 tropomyosin(TM)isoforms TM-αand TM-β(TM-α/-β)in Alectryonella plicatula were identified.The sequences of 852 bp encoding ...Oyster,as a common aquatic food,play an important role in shellfish allergy.In this study,2 tropomyosin(TM)isoforms TM-αand TM-β(TM-α/-β)in Alectryonella plicatula were identified.The sequences of 852 bp encoding 284 amino acids of TM-α/-βand 2 recombinant proteins were obtained,respectively.There were 12 amino acid differences between TM-α/-β.The results of immunological experiments indicated that TM-βhad stronger immunobinding activity and immunoreactivity than those of TM-α.Structural analysis showed that TM-βhad moreα-helix and higher surface hydrophobicity than TM-α.Sequences and epitopes alignment with shellfish TMs revealed that amino acids of TM-βwere more frequently recognized as IgE epitopes in other shellfish TMs than TM-α.Differences in structure and sequence account for the higher immunological activity of TM-βcompared to TM-α.These findings provide a theoretical basis for enriching the understanding of shellfish TM and accurate diagnosis of allergic components.展开更多
Chimeric antigen receptor(CAR)T cell therapy has transformed cancer care and is under investigation for autoimmune,infectious,and chronic inflammatory diseases[1,2].Seven CAR-T cell products have been approved by the ...Chimeric antigen receptor(CAR)T cell therapy has transformed cancer care and is under investigation for autoimmune,infectious,and chronic inflammatory diseases[1,2].Seven CAR-T cell products have been approved by the USA Food and Drug Administration(FDA),demonstrating promising clinical outcomes in the treatment of CD19^(+)B cell malignancies,including acute lymphoblastic leukemia(ALL),non-Hodgkin lymphoma(NHL),chronic lymphocytic leukemia(CLL),and BCMA^(+)multiple myeloma(MM)[3].Key performance indicators for CAR-T cell products encompass high yield,purity,and CAR transduction rates,all of which are crucial for the therapeutic efficacy of the final product.展开更多
A plant fermentation was carried out by Yeast and Lactobaccilli against fermented black turmeric, Kaempferia parviflora (FBT). These materials were proved by as safe in animal safety experiment. We tried to investigat...A plant fermentation was carried out by Yeast and Lactobaccilli against fermented black turmeric, Kaempferia parviflora (FBT). These materials were proved by as safe in animal safety experiment. We tried to investigate changes of immune-competent cells that commonly utilized FBT, including after administration of immno-suppressed animals, the effects by FBT on the regulated effect on the cells were evaluated. Our results showed that FBT augmented the level of lymphocytes in number, while FBT regulated the level of granulocytes in both number and function. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio suggesting their constitution as neutral in peripheral blood were increased significantly 30 days after the administration of FBT in rodents, and compromised host was prepared with cancer chemotherapeutic agent (Mytomycin-C). Our observations showed against intracellular parasite, and that FBT augmented intercellular pathogen through humoral immunity. We discussed the significance and mechanism of FBT on the level of leukocyte subsets in number and function that were considered to be potential indicators for the activation of the compromised host. We also proposed an idea that FBT exhibited tonic effects via activating complement components. The evidences were shown by immune-electrophoretic method. Moreover, we tried to access further to the anti-oxidative activities of this FBT. This modification brought to the significant lift up for antibody producing cells and anti-oxidative activity for phagocytic cells.展开更多
In this study,the effects of three different concentrations（0.5,0.25 and 0.125μl/L）of dichlorvos solution on phenoloxidase（PO）activity,hemolysin activity,peroxidase（POD）activity and antibacterial activity in th...In this study,the effects of three different concentrations（0.5,0.25 and 0.125μl/L）of dichlorvos solution on phenoloxidase（PO）activity,hemolysin activity,peroxidase（POD）activity and antibacterial activity in the serum of Macrobrachium nipponense during four days were investigated.The results indicated that phenoloxidase activity,hemolysin activity,peroxidase activity and antibacterial activity in the serum of Macrobrachium nipponense were improved under the stress of dichlorvos during a short time.With the extension of stress duration and increase of dichlorvos concentration,the activities of various immunological indices were inhibited due to the cumulative effect of dichlorvos in vivo;overall,the reduction increased gradually with the extension of stress duration.展开更多
Eighty sorts of herbs were fermented by Lactobaccilli (f-ESH). This material was proved by as safe in animal safety experiment. This work was aimed to revise the traditional way of hot water extraction to the fermenta...Eighty sorts of herbs were fermented by Lactobaccilli (f-ESH). This material was proved by as safe in animal safety experiment. This work was aimed to revise the traditional way of hot water extraction to the fermentation, in order to use up the original material and searching new activity as well. We tried to prove the new activity by fermentation for immune-competent cells in the host that administrated both of original remedy and the new fermented sample. In rodents, immune-compromised host was prepared with cancer chemotherapeutic agent. Our observations showed that the antigen stimulated animal increased the antibody producing cell for heterologous erythrocyte by compromised host by f-ESH. Moreover, by administration of f-ESH to immno-suppressed hosts, these samples regulated lymphocyte in number and functions, macrophage activities, and regulating anti-oxidative activity by phagocytic cells. The anti-oxidative assay was carried out ex-vivo system by peritoneal excaudate cell that we propose as suitable system for evaluating antioxidative assay. With these evidences, the original COF only augmented the level of lymphocytes in number, while f-ESH regulated the ratio of granulocytes and lymphocyte. In clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was also resulted as neutral in peripheral white blood cells, 1, 2 and 3 weeks after the administration of f-ESH. We discussed the significance and mechanism of cleving complement components Fb by f-ESH in this text. Fb. The new cleavage of complement was directly evident by immune-electrophoretic method. In conclusion, this modification of food materials introduced new style of food intake resulted in the significant regulation such as antibody producing cells and anti-oxidative activity for phagocytic cells comparing traditional processing by hot water extraction.展开更多
T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an init...T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an initial signal of T-cell activation,has been found to occur before IS for-mation.The mechanism for triggering the calcium signaling and relationship bet ween calciumrelease and IS format ion remains unclear.Herein,using live-cell imaging,we found that int ercellularadhesion molecule 1(ICAM-1),an essential mdlecule for IS formation,accumulated and then wasdepleted at the center of the synapse before complete IS formation.During the proces of ICAM1depletion,calcium was released.if ICAM-1 failed to be depleted from the center of the synapse,thesustained calcium signaling could not be induced.Moreover,depletion of ICAM-1 in ISs preferen-tially ccurred with the contact of antigen-specific T-cels and dendritic clls(DCs).Blocking thebinding ofICA M-1 and lymphocy te finction-associated antigen 1(LFA-1),ICAM-1 failed to depleteat the center of the synapse,and calcium release in T-clls decreased.In studying the mechanism ofhow the depletion ofiCA M1 could influence calcium release in T-clls,we found that the movementof ICAM-1 was associat ed with the localization of LFA-1 in the IS,which afected the localization ofcalcium microdomains,ORAIl and mitochondria in IS.Therefore,the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sust ained calcium release in T-cells.展开更多
Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes...Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor＇s HLA antigens in the recipient＇s peripheral blood. Methods： Anti-IL-2 neutralizing monoclonal antibody （anti-IL-2 N-mAb） and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results ： When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection. Conclusion：h suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.展开更多
基金Supported by The grants R21 HL094878 and R21AI10950 to IUS and RGD
文摘The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.
基金Supported by the Research Program of Science and Technology Technology Commission Foundation of Liaoning Province, No. 2001225001-17
文摘AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of rats was established by retrograde injection of 5% sodium taurocholate （1 mL/kg） into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators： decay accelerating factor （DAF; CD55）, 20 ku homologous restriction factor （HRF20; CD59） and membrane cofactor protein （MCP; CEH6）, in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A （n = 21） received no treatment after the SAP model was established; group B （n = 20） was given IL-4 （8 IJg/animal） intraperitoneally 0.5 h before the SAP model was established; group C （n = 20） was given IL-4 （8 μg/animal） intraperitoneaUy 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS： Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis （r = -0.748, -0.827, -0.723; P〈0.01）. In the second series of experiments, no matter when the treatment of IL-4 was given （before or after the induction of SAP model）, the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model （P〈0.01, P〈0.05）, but the expression of MCP was not influenced （P〉0.05）. The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model （P〈0.05）, but the expression of CD59 and MCP did not change （P〉0.05）. CONCLUSION： Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.
文摘A plant fermentation was carried out by Lactobaccilli against the Rhizome from Pueraria milifica (f-PMF). This material was evidenced by safe in animal toxic study. The main aim of this study was to revise the traditional way of hot water extraction to fermentation so as to use up the original material and finding new activity. We tried to show the new activity through phytoestrogen and immune-competent cells from the host that administrated either of original remedy and the new fermented sample, plus activated water SRE. In mice, compromised host was prepared by cancer chemotherapeutic agent (Mitomycin-C). After administration of f-PMF to immno-suppressed animals, the effects by both samples were augmented by lymphocyte in number and functions, macrophage activities, anti-oxidative activity. However, the intense of effect was much more by fermented one but not by conventional one. The anti-oxidative assay was also carried out ex-vivo system by peritoneal macrophage that we proposed as suitable system for evaluating anti-oxidative assay. In our clinical study by 20 healthy volunteers, granulocyte and lymphocyte ratio was regulated as neutral in peripheral white blood cells, increasing one, two and three weeks after the administration of f-PMF. We have found the significant regulation of blood chemical factors that were important makers for the lifestyle-related diseases. The mechanism of augmentation by probing directory with immuno-electrophoretic method, generating new complement component, especially found by alternative pathway of complement. So we discussed the process concerning designed f-PMF molecule for activation of complement component and bound for the biological activity of each physical component. In a limited condition, fewer numbers of volunteers, the breast size was tending to increase along with the administration time. Including these evidences, we discussed the possibility of this traditional ethnic medicine, originally found and spread in the highland area in Thailand and Myanmar.
文摘Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity,insulin resistance,diabetes,dyslipidemia,and atherosclerosis.The complement system was originally viewed as a supportive first line of defense against microbial invaders,and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes,involving in such diverse processes as clearance of the immune complexes,complementing T and B cell immune functions,tissue regeneration,and metabolism.The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity,insulin resistance and diabetes mellitus.In addition,we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy,nephropathy and neuropathy,highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.
基金Supported by Natural Science Foundation of Guangxi,No.2020GXNSFDA238006Special Fund of the Central Government Guiding Local Scientific and Technological Development by Guangxi Science and Technology Department,No.GuikeZY21195024Research Enhancement Project for Junior Faculty in Higher Education Institutes of Guangxi,No.2018KY0419.
文摘BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.AIM To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.METHODS A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment.We detected the effects of C2-FH on liver function,inflammatory response and complement activation.Additionally,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.RESULTS C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by APAP.Moreover,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury.RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.CONCLUSION C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.
基金National Natural Science Foundation of China(No, 39630296 )
文摘Objective: To study the mechanism of T-cell activation induced by non-lethal complement attack and the role of CD59 in this process. Methods: Human CD59 and its transmentbrane counterpart CD59TM cDNA were transfected into murine thymoma EL-4 cells. Activation and proliferation of EL-4 transfectants were observed with MIT assay. Results:Both CD59 and CD59 TM cDNA expressed on EL-4 cells effectively inhibited complement-mediated membrane damage. Cross-linking of CD59 with antibody induced activation of CD59/EL-4 cells but not CDS9TM/EL-4 cells. This effect was inhibited by Herbimycin A. a special protein tyrosine kinase (PTK) inhibitor. Non-lethal complement attack induced CD59/EL-4 but not CD59TMIEL-4 cell to proliferate, and this reaction was not blocked by Herbimycin A. Conclusion: CD59 takes part in T cell activation induced by non-lethal complement attack. The mechanisms of T cell activation induced by non-lethal complement attack arc different from those by cross-linking of CD59.
基金financial support received from the Anhui Provincial Excellent Scientific Research and Innovation Team(2023AH010050)the Key Research and Development Plan of Anhui Province(202204c06020013,202204c06020029)+1 种基金the“Biology and Medicine”key subject of Hefei University(2023xk05)the open research project of Anhui Ecological Fermentation Engineering Research Center for Functional Fruit Beverage(FSKFKT015)。
文摘In this study,polysaccharides were extracted from blueberry fruit(BFP)and isolated to 3 components(BFP-1,BFP-2 and BFP-3).The molecular weight,monosaccharide composition,characteristic groups,microscopic morphology,and triple helical conformation of the polysaccharides were characterized using high performance permeation chromatography,high performance liquid chromatography,gas chromatographymass spectrometry,Fourier transform infrared spectrometer,scanning electron microscope and Congo red staining.Moreover,the hypolipidemic and immunological activities of the polysaccharides were also assessed.Results showed that the molecular weights of polysaccharides BFP-1,BFP-2,and BFP-3 were 5.547×10^(4),5.671×10^(4),and 3.951×10^(4)Da,respectively,the main monosaccharides were glucose(Glc),galactose(Gal)and arabinose(Ara),but BFP-3 was mainly composed of galacturonic acid(Gal A),Glc,Gal,and Ara.The backbone of BFP-1 was→4)-Glcp-(1→,which branches to Ara and xylose(Xyl)residues,while the backbone of BFP-2 was→5)-Araf-(1→,which branches to Xyl,Glc,rhamnose(Rha)and Gal residues,in particularly,BFP-3 has a more complex branching with a→3,6)-Galp-(1→)backbone,the side chain is dominated by Araf-(1→).Blueberry polysaccharides are pyran-type polysaccharides withα-glycosidic bonds,and BFP-1 has a typical triple-helical structure.The activity assay revealed that the binding of BFP-3 to sodium glycylcholate hydrate and sodium taurocholate was 79.95%and 78.50%,respectively,indicating that it had better hypolipidemic activity than the others.Immunoactivity assay showed that BFP promoted NO secretion through activating the NF-κB signalling pathway in RAW264.7 cells,which played a role in enhancing the immune function of the organism.These findings may provide a reference for the development and application of blueberry polysaccharides in functional food and medicine.
文摘in order to verify whether the bactericidal capacity of polymorphonuclear neutrophils (PMNs)could be abolished by the bypass-activated complement,intracellular bactericidal activity (ICBA),superoxide ions (O2-) and specific granules (SGs) 3 were determine
基金Supported partially by National Natural Science Foundation of China(No.81271033,81470621)
文摘AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.
基金supported by the National Natural Scientific Foundation of China(32072336,32472449).
文摘Oyster,as a common aquatic food,play an important role in shellfish allergy.In this study,2 tropomyosin(TM)isoforms TM-αand TM-β(TM-α/-β)in Alectryonella plicatula were identified.The sequences of 852 bp encoding 284 amino acids of TM-α/-βand 2 recombinant proteins were obtained,respectively.There were 12 amino acid differences between TM-α/-β.The results of immunological experiments indicated that TM-βhad stronger immunobinding activity and immunoreactivity than those of TM-α.Structural analysis showed that TM-βhad moreα-helix and higher surface hydrophobicity than TM-α.Sequences and epitopes alignment with shellfish TMs revealed that amino acids of TM-βwere more frequently recognized as IgE epitopes in other shellfish TMs than TM-α.Differences in structure and sequence account for the higher immunological activity of TM-βcompared to TM-α.These findings provide a theoretical basis for enriching the understanding of shellfish TM and accurate diagnosis of allergic components.
文摘Chimeric antigen receptor(CAR)T cell therapy has transformed cancer care and is under investigation for autoimmune,infectious,and chronic inflammatory diseases[1,2].Seven CAR-T cell products have been approved by the USA Food and Drug Administration(FDA),demonstrating promising clinical outcomes in the treatment of CD19^(+)B cell malignancies,including acute lymphoblastic leukemia(ALL),non-Hodgkin lymphoma(NHL),chronic lymphocytic leukemia(CLL),and BCMA^(+)multiple myeloma(MM)[3].Key performance indicators for CAR-T cell products encompass high yield,purity,and CAR transduction rates,all of which are crucial for the therapeutic efficacy of the final product.
文摘A plant fermentation was carried out by Yeast and Lactobaccilli against fermented black turmeric, Kaempferia parviflora (FBT). These materials were proved by as safe in animal safety experiment. We tried to investigate changes of immune-competent cells that commonly utilized FBT, including after administration of immno-suppressed animals, the effects by FBT on the regulated effect on the cells were evaluated. Our results showed that FBT augmented the level of lymphocytes in number, while FBT regulated the level of granulocytes in both number and function. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio suggesting their constitution as neutral in peripheral blood were increased significantly 30 days after the administration of FBT in rodents, and compromised host was prepared with cancer chemotherapeutic agent (Mytomycin-C). Our observations showed against intracellular parasite, and that FBT augmented intercellular pathogen through humoral immunity. We discussed the significance and mechanism of FBT on the level of leukocyte subsets in number and function that were considered to be potential indicators for the activation of the compromised host. We also proposed an idea that FBT exhibited tonic effects via activating complement components. The evidences were shown by immune-electrophoretic method. Moreover, we tried to access further to the anti-oxidative activities of this FBT. This modification brought to the significant lift up for antibody producing cells and anti-oxidative activity for phagocytic cells.
文摘In this study,the effects of three different concentrations（0.5,0.25 and 0.125μl/L）of dichlorvos solution on phenoloxidase（PO）activity,hemolysin activity,peroxidase（POD）activity and antibacterial activity in the serum of Macrobrachium nipponense during four days were investigated.The results indicated that phenoloxidase activity,hemolysin activity,peroxidase activity and antibacterial activity in the serum of Macrobrachium nipponense were improved under the stress of dichlorvos during a short time.With the extension of stress duration and increase of dichlorvos concentration,the activities of various immunological indices were inhibited due to the cumulative effect of dichlorvos in vivo;overall,the reduction increased gradually with the extension of stress duration.
文摘Eighty sorts of herbs were fermented by Lactobaccilli (f-ESH). This material was proved by as safe in animal safety experiment. This work was aimed to revise the traditional way of hot water extraction to the fermentation, in order to use up the original material and searching new activity as well. We tried to prove the new activity by fermentation for immune-competent cells in the host that administrated both of original remedy and the new fermented sample. In rodents, immune-compromised host was prepared with cancer chemotherapeutic agent. Our observations showed that the antigen stimulated animal increased the antibody producing cell for heterologous erythrocyte by compromised host by f-ESH. Moreover, by administration of f-ESH to immno-suppressed hosts, these samples regulated lymphocyte in number and functions, macrophage activities, and regulating anti-oxidative activity by phagocytic cells. The anti-oxidative assay was carried out ex-vivo system by peritoneal excaudate cell that we propose as suitable system for evaluating antioxidative assay. With these evidences, the original COF only augmented the level of lymphocytes in number, while f-ESH regulated the ratio of granulocytes and lymphocyte. In clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was also resulted as neutral in peripheral white blood cells, 1, 2 and 3 weeks after the administration of f-ESH. We discussed the significance and mechanism of cleving complement components Fb by f-ESH in this text. Fb. The new cleavage of complement was directly evident by immune-electrophoretic method. In conclusion, this modification of food materials introduced new style of food intake resulted in the significant regulation such as antibody producing cells and anti-oxidative activity for phagocytic cells comparing traditional processing by hot water extraction.
基金supported by the National Major Scientic Research Program of China(Grant No.2011CB910404)the National Nature Science Foundation of China(Grant Nos.61227017,31400772 and 81273215)+3 种基金the National Science Fund for Distinguished Young Scholars(Grant No.61425006)the grants of the Project for Laureate of Taishan Scholar(Grant No.ts201511075)the Innovation Project of Shandong Academy of Medical Sciences,the Projects of medical and health technology development program in Shandong province(No.2015WS0194)the science and technology program from Shandong Academy of Medical Sciences(No.2015-25).
文摘T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an initial signal of T-cell activation,has been found to occur before IS for-mation.The mechanism for triggering the calcium signaling and relationship bet ween calciumrelease and IS format ion remains unclear.Herein,using live-cell imaging,we found that int ercellularadhesion molecule 1(ICAM-1),an essential mdlecule for IS formation,accumulated and then wasdepleted at the center of the synapse before complete IS formation.During the proces of ICAM1depletion,calcium was released.if ICAM-1 failed to be depleted from the center of the synapse,thesustained calcium signaling could not be induced.Moreover,depletion of ICAM-1 in ISs preferen-tially ccurred with the contact of antigen-specific T-cels and dendritic clls(DCs).Blocking thebinding ofICA M-1 and lymphocy te finction-associated antigen 1(LFA-1),ICAM-1 failed to depleteat the center of the synapse,and calcium release in T-clls decreased.In studying the mechanism ofhow the depletion ofiCA M1 could influence calcium release in T-clls,we found that the movementof ICAM-1 was associat ed with the localization of LFA-1 in the IS,which afected the localization ofcalcium microdomains,ORAIl and mitochondria in IS.Therefore,the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sust ained calcium release in T-cells.
文摘Objective：With the regular mixed lymphocytes culture （MLC） to detect the allograft rejection, the reactivity of the activated lymphocytes （primed lymphocytes） of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor＇s HLA antigens in the recipient＇s peripheral blood. Methods： Anti-IL-2 neutralizing monoclonal antibody （anti-IL-2 N-mAb） and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results ： When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection. Conclusion：h suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.
