杨树菇血凝素糖识别域与禽流感病毒H_9N_2表面糖蛋白结合介导的佐剂效果（英文）
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摘要
目的:探讨杨树菇血凝素(AAL)作为疫苗佐剂的作用机理,为有囊膜病毒疫苗佐剂的研究提供新思路和数据。创新点:首次研究AAL作为禽流感疫苗佐剂的作用机理。方法:大肠杆菌重组表达、纯化野生型的AAL(AAL-wt)和糖识别结构域(CRD)突变型的AAL(AAL-mut R63H)(图1);动物试验证实AAL-wt具有免疫佐剂活性,AAL-mut R63H失去免疫佐剂活性(图2);免疫胶体金电镜(immunogold electron microscopy,IEM)试验发现AAL-wt能吸附H_9N_2病毒粒子,而AAL-mut R63H不能吸附病毒粒子(图4);凝集素印迹(lectin blot)、免疫共沉淀(co-immunoprecipitation,Co-IP)试验证明了CRD区与H_9N_2病毒中血球凝集素(HA)和神经氨酸酶(NA)这两种糖蛋白的相互作用(图5)。结论:AAL的CRD区是发挥佐剂作用的关键区域,CRD区与禽流感病毒表面的HA糖蛋白结合,可能暴露病毒的免疫识别位点,或者将病毒粒子连接在一起,形成大的病毒复合体,增加病毒的抗原性(图6)。
Objective: To evaluate the potential adjuvant effect of Agrocybe aegerita lectin(AAL), which was isolated from mushroom, against a virulent H_9N_2 strain in vivo and in vitro. Methods: In trial 1, 50 BALB/c male mice(8 weeks old) were divided into five groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(control), inactivated H_9N_2+0.2%(w/w) alum, inactivated H_9N_2+0.5 mg recombinant AAL/kg body weight(BW), inactivated H_9N_2+1.0 mg AAL/kg BW, and inactivated H_9N_2+2.5 mg AAL/kg BW, respectively, four times at 7-d intervals. In trial 2, 30 BALB/c male mice(8 weeks old) were divided into three groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(control), inactivated H_9N_2+2.5 mg recombinant wild-type AAL(AAL-wt)/kg BW, and inactivated H_9N_2+2.5 mg carbohydrate recognition domain(CRD) mutant AAL(AAL-mut R63H)/kg BW, respectively, four times at 7-d intervals. Seven days after the final immunization, serum samples were collected from each group for analysis. Hemagglutination assay, immunogold electron microscope, lectin blotting, and coimmunoprecipitation were used to study the interaction between AAL and H_9N_2 in vitro. Results: Ig G, Ig G1, and Ig G2 a antibody levels were significantly increased in the sera of mice co-immunized with inactivated H_9N_2 and AAL when compared to mice immunized with inactivated H_9N_2 alone. No significant increase of the Ig G antibody level was detected in the sera of the mice co-immunized with inactivated H_9N_2 and AAL-mut R63 H. Moreover, AAL-wt, but not mutant AAL-mut R63 H, adhered to the surface of H_9N_2 virus. The interaction between AAL and the H_9N_2 virus was further demonstrated to be associated with the CRD of AAL binding to the surface glycosylated proteins, hemagglutinin and neuraminidase. Conclusions: Our findings indicated that AAL could be a safe and effective adjuvant capable of boosting humoral immunity against H_9N_2 viruses in mice through its interaction with the viral surface glycosylated proteins, hemagglutinin and neuraminidase.
Objective: To evaluate the potential adjuvant effect of Agrocybe aegerita lectin(AAL), which was isolated from mushroom, against a virulent H_9N_2 strain in vivo and in vitro. Methods: In trial 1, 50 BALB/c male mice(8 weeks old) were divided into five groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(control), inactivated H_9N_2+0.2%(w/w) alum, inactivated H_9N_2+0.5 mg recombinant AAL/kg body weight(BW), inactivated H_9N_2+1.0 mg AAL/kg BW, and inactivated H_9N_2+2.5 mg AAL/kg BW, respectively, four times at 7-d intervals. In trial 2, 30 BALB/c male mice(8 weeks old) were divided into three groups(n=10 each group) which received a subcutaneous injection of inactivated H_9N_2(control), inactivated H_9N_2+2.5 mg recombinant wild-type AAL(AAL-wt)/kg BW, and inactivated H_9N_2+2.5 mg carbohydrate recognition domain(CRD) mutant AAL(AAL-mut R63H)/kg BW, respectively, four times at 7-d intervals. Seven days after the final immunization, serum samples were collected from each group for analysis. Hemagglutination assay, immunogold electron microscope, lectin blotting, and coimmunoprecipitation were used to study the interaction between AAL and H_9N_2 in vitro. Results: Ig G, Ig G1, and Ig G2 a antibody levels were significantly increased in the sera of mice co-immunized with inactivated H_9N_2 and AAL when compared to mice immunized with inactivated H_9N_2 alone. No significant increase of the Ig G antibody level was detected in the sera of the mice co-immunized with inactivated H_9N_2 and AAL-mut R63 H. Moreover, AAL-wt, but not mutant AAL-mut R63 H, adhered to the surface of H_9N_2 virus. The interaction between AAL and the H_9N_2 virus was further demonstrated to be associated with the CRD of AAL binding to the surface glycosylated proteins, hemagglutinin and neuraminidase. Conclusions: Our findings indicated that AAL could be a safe and effective adjuvant capable of boosting humoral immunity against H_9N_2 viruses in mice through its interaction with the viral surface glycosylated proteins, hemagglutinin and neuraminidase.
引文
Aguilar,J.C.,Rodríguez,E.G.,2007.Vaccine adjuvants revisited.Vaccine,25(19):3752-3762.http://dx.doi.org/10.1016/j.vaccine.2007.01.111
Choi,J.G.,Lee,Y.J.,Kim,Y.J.,et al.,2008.An inactivated vaccine to control the current H9N2 low pathogenic avian influenza in Korea.J.Vet.Med.Sci.,9(9):67-74.http://dx.doi.org/10.4142/jvs.2008.9.1.6
Dabaghian,M.,Latify,A.M.,Tebianian,M.,et al.,2014.Vaccination with recombinant 4×M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens.Vet.Microbiol.,174(1-2):116-126.http://dx.doi.org/10.1016/j.vetmic.2014.09.009
Dodson,J.M.,Lenkowski,P.W.,Eubanks,A.C.,et al.,1999.Infection and immunity mediated by the carbohydrate recognition domain of the Entamoeba histolytica Gal/Gal NAc lectin.J.Infect.Dis.,179(2):460-466.http://dx.doi.org/10.1086/314610
Feng,L.,Sun,H.,Zhang,Y.,et al.,2010.Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.FASEB J.,24(10):3861-3868.http://dx.doi.org/10.1096/fj.10-159111
Gao,W.,Sun,Y.,Chen,S.,et al.,2013.Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBs Ag-transgenic mice.Vaccine,31(18):2273-2280.http://dx.doi.org/10.1016/j.vaccine.2013.02.062
Huang,L.,Ikejiri,A.,Shimizu,Y.,et al.,2008.Immunoadjuvant activity of crude lectin extracted from Momordica charantia seed.J.Vet.Med.Sci.,70(5):533-535.http://dx.doi.org/10.1292/jvms.70.533
Jung,H.J.,Kim,Y.H.,Song,T.J.,et al.,2011.Adjuvant effect of Korean mistletoe lectin on mucosal immunity induction following intranasal immunization with hemagglutinin antigen.Food Sci.Biotechnol.,20(3):629-634.http://dx.doi.org/10.1007/s10068-011-0089-3
Kim,J.C.,Yoon,T.J.,Song,T.J.,et al.,2011.Mucosal immunoadjuvant activity of Korean mistletoe lectin-C.Korean J.Food Sci.Technol.,43(1):72-76.http://dx.doi.org/10.9721/KJFST.2011.43.1.072
Klenk,H.D.,Wagner,R.,Heuer,D.,et al.,2001.Importance of hemagglutinin glycosylation for the biological functions of influenza virus.Virus Res.,82(1-2):73-75.http://dx.doi.org/10.1016/S0168-1702(01)00389-6
Kong,X.,Rui,R.,Li,X.,et al.,2004.Effects of Chinese herbal medicinal ingredients on peripheral lymphocyte proliferation and serum antibody titer after vaccination in chicken.Int.Immunopharmacol.,4(7):975-982.http://dx.doi.org/10.1016/j.intimp.2004.03.008
Kong,X.F.,Hu,Y.L.,Yin,Y.L.,et al.,2006.Chinese herbal ingredients are effective immune stimulators for chickens infected with the Newcastle disease virus.Poultry Sci.,85(12):2169-2175.http://dx.doi.org/10.1093/ps/85.12.2169
Kreisman,L.S.,Cobb,B.A.,2012.Infection,inflammation and host carbohydrates:a Glyco-Evasion Hypothesis.Glycobiology,22(8):1019-1030.http://dx.doi.org/10.1093/glycob/cws070
Li,D.,Xue,M.,Wang,C.,et al.,2011.Bursopentine as a novel immunoadjuvant enhances both humoral and cell-mediated immune responses to inactivated H9N2avian influenza virus in chickens.Clin.Vacc.Immunol.,18(9):1497-1502.http://dx.doi.org/10.1128/CVI.05133-11
Lindblad,E.B.,2004.Aluminium compounds for use in vaccines.Immunol.Cell Biol.,82(5):497-505.http://dx.doi.org/10.1111/j.0818-9641.2004.01286.x
Liu,J.H.,Okazaki,K.,Shi,W.M.,et al.,2003.Phylogenetic analysis of hemagglutinin and neuraminidase genes of H9N2 viruses isolated from migratory ducks.Virus Genes,27(3):291-296.http://dx.doi.org/10.1023/A:1026304117797
Liu,M.A.,1998.Vaccine developments.Nat.Med.,4(5):515-519.http://dx.doi.org/10.1038/nm0598supp-515
Matsumura,K.,Higashida,K.,Ishida,H.,et al.,2007.Carbohydrate binding specificity of a fucose-specific lectin from Aspergillus oryzae:a novel probe for core fucose.J.Biol.Chem.,282(21):15700-15708.http://dx.doi.org/10.1074/jbc.M701195200
Pena,L.,Sutton,T.,Chockalingam,A.,et al.,2013.Influenza viruses with rearranged genomes as live-attenuated vaccines.J.Virol.,87(9):5118-5127.http://dx.doi.org/10.1128/JVI.02490-12
Rabinovich,G.,Croci,D.,2012.Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer.Immunity,36(3):322-335.http://dx.doi.org/10.1016/j.immuni.2012.03.004
Rahman,M.M.,Uyangaa,E.,Han,Y.W.,et al.,2012.Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-αand interleukin-18 along with an inactivated vaccine.BMC Vet.Res.,8:105.http://dx.doi.org/10.1186/1746-6148-8-105
Rajik,M.,Jahanshiri,F.,Omar,A.R.,et al.,2009.Identification and characterisation of a novel anti-viral peptide against avian influenza virus H9N2.Virol.J.,6:74.http://dx.doi.org/10.1186/1743-422X-6-74
Rajput,Z.I.,Hu,S.H.,Xiao,C.W.,et al.,2007.Adjuvant effects of saponins on animal immune responses.J.Zhejiang Univ.-Sci.B(Biomed.&Biotechnol.),8(3):153-161.http://dx.doi.org/10.1631/jzus.2007.B0153
Reitter,J.N.,Means,R.E.,Desrosiers,R.C.,1998.A role for carbohydrates in immune evasion in AIDS.Nat.Med.,4(6):679-684.http://dx.doi.org/10.1038/nm0698-679
Sivakumar,S.M.,Safhi,M.M.,Kannadasan,M.,et al.,2011.Vaccine adjuvants-current status and prospects on controlled release adjuvancity.Saudi Pharm.J.,19(4):197-206.http://dx.doi.org/10.1016/j.jsps.2011.06.003
Sun,H.,Zhao,C.G.,Tong,X.,et al.,2003.A lectin with mycelia differentiation and antiphytovirus activities from the edible mushroom Agrocybe aegerita.J.Biochem.Mol.Biol.,36(2):214-222.http://dx.doi.org/10.5483/BMBRep.2003.36.2.214
Sun,L.H.,Li,J.G.,Zhao,H.,et al.,2013.Porcine serum can be biofortified with selenium to inhibit proliferation of three types of human cancer cells.J.Nutr.,143(7):1115-1122.http://dx.doi.org/10.3945/jn.113.177410
Sun,L.H.,Lei,M.Y.,Zhang,N.Y.,et al.,2014.Hepatotoxic effects of mycotoxin combinations in mice.Food Chem.Toxicol.,74:289-293.http://dx.doi.org/10.1016/j.fct.2014.10.020
Sun,Y.,Liu,J.,2008.Adjuvant effect of water-soluble polysaccharide(PAP)from the mycelium of Polyporus albicans on the immune responses to ovalbumin in mice.Vaccine,26(31):3932-3936.http://dx.doi.org/10.1016/j.vaccine.2008.04.018
Tsuchiya,E.,Sugawara,K.,Hongo,S.,et al.,2002a.Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule.J.Gen.Virol.,83(5):1137-1146.http://dx.doi.org/10.1099/0022-1317-83-5-1137
Tsuchiya,E.,Sugawara,K.,Hongo,S.,et al.,2002b.Role of overlapping glycosylation sequons in antigenic properties,intracellular transport and biological activities of influenza A/H2N2 virus haemagglutinin.J.Gen.Virol.,83(12):3067-3074.http://dx.doi.org/10.1099/0022-1317-83-12-3067
Ung,C.Y.,Li,H.,Kong,C.Y.,et al.,2007.Usefulness of traditionally defined herbal properties for distinguishing prescriptions of traditional Chinese medicine from nonprescription recipes.J.Ethnopharmacol.,109(1):21-28.http://dx.doi.org/10.1016/j.jep.2006.06.007
Yamaguchi,N.,Sonoyama,K.,Kikuchi,H.,et al.,2005.Gastric colonization of Candida albicans differs in mice fed commercial and purified diets.J.Nutr.,135(1):109-115.
Yang,L.,Hu,Y.,Xue,J.,et al.,2008.Compound Chinese herbal medicinal ingredients can enhance immune response and efficacy of RHD vaccine in rabbit.Vaccine,26(35):4451-4455.http://dx.doi.org/10.1016/j.vaccine.2008.06.075
Yang,N.,Tong,X.,Xiang,Y.,et al.,2005.Molecular character of the recombinant antitumor lectin from the edible mushroom Agrocybe aegerita.J.Biochem.,138(2):145-150.http://dx.doi.org/10.1093/jb/mvi109
Liang,Y.,Lei,F.,Xin,T.,et al.,2009.Importance of nuclear localization for the apoptosis-induced activity of a fungal galectin AAL(Agrocybe aegerita lectin).Biochem.Biophys.Res.Commun.,386(3):437-442.http://dx.doi.org/10.1016/j.bbrc.2009.06.054
Zhao,C.,Sun,H.,Tong,X.,et al.,2003.An antitumour lectin from the edible mushroom Agrocybe aegerita.Biochem.J.,374(2):321-327.http://dx.doi.org/10.1042/bj20030300
Choi,J.G.,Lee,Y.J.,Kim,Y.J.,et al.,2008.An inactivated vaccine to control the current H9N2 low pathogenic avian influenza in Korea.J.Vet.Med.Sci.,9(9):67-74.http://dx.doi.org/10.4142/jvs.2008.9.1.6
Dabaghian,M.,Latify,A.M.,Tebianian,M.,et al.,2014.Vaccination with recombinant 4×M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens.Vet.Microbiol.,174(1-2):116-126.http://dx.doi.org/10.1016/j.vetmic.2014.09.009
Dodson,J.M.,Lenkowski,P.W.,Eubanks,A.C.,et al.,1999.Infection and immunity mediated by the carbohydrate recognition domain of the Entamoeba histolytica Gal/Gal NAc lectin.J.Infect.Dis.,179(2):460-466.http://dx.doi.org/10.1086/314610
Feng,L.,Sun,H.,Zhang,Y.,et al.,2010.Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.FASEB J.,24(10):3861-3868.http://dx.doi.org/10.1096/fj.10-159111
Gao,W.,Sun,Y.,Chen,S.,et al.,2013.Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBs Ag-transgenic mice.Vaccine,31(18):2273-2280.http://dx.doi.org/10.1016/j.vaccine.2013.02.062
Huang,L.,Ikejiri,A.,Shimizu,Y.,et al.,2008.Immunoadjuvant activity of crude lectin extracted from Momordica charantia seed.J.Vet.Med.Sci.,70(5):533-535.http://dx.doi.org/10.1292/jvms.70.533
Jung,H.J.,Kim,Y.H.,Song,T.J.,et al.,2011.Adjuvant effect of Korean mistletoe lectin on mucosal immunity induction following intranasal immunization with hemagglutinin antigen.Food Sci.Biotechnol.,20(3):629-634.http://dx.doi.org/10.1007/s10068-011-0089-3
Kim,J.C.,Yoon,T.J.,Song,T.J.,et al.,2011.Mucosal immunoadjuvant activity of Korean mistletoe lectin-C.Korean J.Food Sci.Technol.,43(1):72-76.http://dx.doi.org/10.9721/KJFST.2011.43.1.072
Klenk,H.D.,Wagner,R.,Heuer,D.,et al.,2001.Importance of hemagglutinin glycosylation for the biological functions of influenza virus.Virus Res.,82(1-2):73-75.http://dx.doi.org/10.1016/S0168-1702(01)00389-6
Kong,X.,Rui,R.,Li,X.,et al.,2004.Effects of Chinese herbal medicinal ingredients on peripheral lymphocyte proliferation and serum antibody titer after vaccination in chicken.Int.Immunopharmacol.,4(7):975-982.http://dx.doi.org/10.1016/j.intimp.2004.03.008
Kong,X.F.,Hu,Y.L.,Yin,Y.L.,et al.,2006.Chinese herbal ingredients are effective immune stimulators for chickens infected with the Newcastle disease virus.Poultry Sci.,85(12):2169-2175.http://dx.doi.org/10.1093/ps/85.12.2169
Kreisman,L.S.,Cobb,B.A.,2012.Infection,inflammation and host carbohydrates:a Glyco-Evasion Hypothesis.Glycobiology,22(8):1019-1030.http://dx.doi.org/10.1093/glycob/cws070
Li,D.,Xue,M.,Wang,C.,et al.,2011.Bursopentine as a novel immunoadjuvant enhances both humoral and cell-mediated immune responses to inactivated H9N2avian influenza virus in chickens.Clin.Vacc.Immunol.,18(9):1497-1502.http://dx.doi.org/10.1128/CVI.05133-11
Lindblad,E.B.,2004.Aluminium compounds for use in vaccines.Immunol.Cell Biol.,82(5):497-505.http://dx.doi.org/10.1111/j.0818-9641.2004.01286.x
Liu,J.H.,Okazaki,K.,Shi,W.M.,et al.,2003.Phylogenetic analysis of hemagglutinin and neuraminidase genes of H9N2 viruses isolated from migratory ducks.Virus Genes,27(3):291-296.http://dx.doi.org/10.1023/A:1026304117797
Liu,M.A.,1998.Vaccine developments.Nat.Med.,4(5):515-519.http://dx.doi.org/10.1038/nm0598supp-515
Matsumura,K.,Higashida,K.,Ishida,H.,et al.,2007.Carbohydrate binding specificity of a fucose-specific lectin from Aspergillus oryzae:a novel probe for core fucose.J.Biol.Chem.,282(21):15700-15708.http://dx.doi.org/10.1074/jbc.M701195200
Pena,L.,Sutton,T.,Chockalingam,A.,et al.,2013.Influenza viruses with rearranged genomes as live-attenuated vaccines.J.Virol.,87(9):5118-5127.http://dx.doi.org/10.1128/JVI.02490-12
Rabinovich,G.,Croci,D.,2012.Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer.Immunity,36(3):322-335.http://dx.doi.org/10.1016/j.immuni.2012.03.004
Rahman,M.M.,Uyangaa,E.,Han,Y.W.,et al.,2012.Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-αand interleukin-18 along with an inactivated vaccine.BMC Vet.Res.,8:105.http://dx.doi.org/10.1186/1746-6148-8-105
Rajik,M.,Jahanshiri,F.,Omar,A.R.,et al.,2009.Identification and characterisation of a novel anti-viral peptide against avian influenza virus H9N2.Virol.J.,6:74.http://dx.doi.org/10.1186/1743-422X-6-74
Rajput,Z.I.,Hu,S.H.,Xiao,C.W.,et al.,2007.Adjuvant effects of saponins on animal immune responses.J.Zhejiang Univ.-Sci.B(Biomed.&Biotechnol.),8(3):153-161.http://dx.doi.org/10.1631/jzus.2007.B0153
Reitter,J.N.,Means,R.E.,Desrosiers,R.C.,1998.A role for carbohydrates in immune evasion in AIDS.Nat.Med.,4(6):679-684.http://dx.doi.org/10.1038/nm0698-679
Sivakumar,S.M.,Safhi,M.M.,Kannadasan,M.,et al.,2011.Vaccine adjuvants-current status and prospects on controlled release adjuvancity.Saudi Pharm.J.,19(4):197-206.http://dx.doi.org/10.1016/j.jsps.2011.06.003
Sun,H.,Zhao,C.G.,Tong,X.,et al.,2003.A lectin with mycelia differentiation and antiphytovirus activities from the edible mushroom Agrocybe aegerita.J.Biochem.Mol.Biol.,36(2):214-222.http://dx.doi.org/10.5483/BMBRep.2003.36.2.214
Sun,L.H.,Li,J.G.,Zhao,H.,et al.,2013.Porcine serum can be biofortified with selenium to inhibit proliferation of three types of human cancer cells.J.Nutr.,143(7):1115-1122.http://dx.doi.org/10.3945/jn.113.177410
Sun,L.H.,Lei,M.Y.,Zhang,N.Y.,et al.,2014.Hepatotoxic effects of mycotoxin combinations in mice.Food Chem.Toxicol.,74:289-293.http://dx.doi.org/10.1016/j.fct.2014.10.020
Sun,Y.,Liu,J.,2008.Adjuvant effect of water-soluble polysaccharide(PAP)from the mycelium of Polyporus albicans on the immune responses to ovalbumin in mice.Vaccine,26(31):3932-3936.http://dx.doi.org/10.1016/j.vaccine.2008.04.018
Tsuchiya,E.,Sugawara,K.,Hongo,S.,et al.,2002a.Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule.J.Gen.Virol.,83(5):1137-1146.http://dx.doi.org/10.1099/0022-1317-83-5-1137
Tsuchiya,E.,Sugawara,K.,Hongo,S.,et al.,2002b.Role of overlapping glycosylation sequons in antigenic properties,intracellular transport and biological activities of influenza A/H2N2 virus haemagglutinin.J.Gen.Virol.,83(12):3067-3074.http://dx.doi.org/10.1099/0022-1317-83-12-3067
Ung,C.Y.,Li,H.,Kong,C.Y.,et al.,2007.Usefulness of traditionally defined herbal properties for distinguishing prescriptions of traditional Chinese medicine from nonprescription recipes.J.Ethnopharmacol.,109(1):21-28.http://dx.doi.org/10.1016/j.jep.2006.06.007
Yamaguchi,N.,Sonoyama,K.,Kikuchi,H.,et al.,2005.Gastric colonization of Candida albicans differs in mice fed commercial and purified diets.J.Nutr.,135(1):109-115.
Yang,L.,Hu,Y.,Xue,J.,et al.,2008.Compound Chinese herbal medicinal ingredients can enhance immune response and efficacy of RHD vaccine in rabbit.Vaccine,26(35):4451-4455.http://dx.doi.org/10.1016/j.vaccine.2008.06.075
Yang,N.,Tong,X.,Xiang,Y.,et al.,2005.Molecular character of the recombinant antitumor lectin from the edible mushroom Agrocybe aegerita.J.Biochem.,138(2):145-150.http://dx.doi.org/10.1093/jb/mvi109
Liang,Y.,Lei,F.,Xin,T.,et al.,2009.Importance of nuclear localization for the apoptosis-induced activity of a fungal galectin AAL(Agrocybe aegerita lectin).Biochem.Biophys.Res.Commun.,386(3):437-442.http://dx.doi.org/10.1016/j.bbrc.2009.06.054
Zhao,C.,Sun,H.,Tong,X.,et al.,2003.An antitumour lectin from the edible mushroom Agrocybe aegerita.Biochem.J.,374(2):321-327.http://dx.doi.org/10.1042/bj20030300