Chiral materials with the same atomic compositions exhibit different chemical,physical,and biological properties because of their distinct spatial structures.Herein,a chiral strategy was proposed to develop poly(lacti...Chiral materials with the same atomic compositions exhibit different chemical,physical,and biological properties because of their distinct spatial structures.Herein,a chiral strategy was proposed to develop poly(lactic acid)(PLA)nanoparticle as an efficient nanoadjuvant to activate adaptive anticancer immunity.Two chiral nanovaccines were prepared by directly mixing amino-terminated PLA(PLLA-NH2 or PDLA-NH2)with the model protein antigen ovalbumin(OVA).After being injected into mice subcutaneously,both nanovaccines efficiently migrated to the lymph nodes to initiate the sequential anticancer immune responses.Compared with the PLLA nanovaccine(PLLA-OVA),the PDLA one(PDLA-OVA)contributed to more robust dendritic cell(DC)maturation,antigen presentation,and T lymphocyte activation.In addition to the activation of cellular immunity,PDLA-OVA also triggered a more vigorous activation of humoral immunity,which induced the production of more anti-OVA immunoglobulin G(IgG)than PLLA-OVA.When used as prophylactic or therapeutic nanovaccine toward murine melanoma models,PDLA-OVA triggered more potent adaptive anticancer immune responses that more effectively inhibited the cancer genesis and progression,indicating the significant potential of immunologically effective PDLA nanoadjuvant in cancer immunotherapy.展开更多
Objective To investigate the effect of Yinlai Decoction(YD)on the microstructure of colon,and activity of D-lactic acid(DLA)and diamine oxidase(DAO)in serum of pneumonia mice model fed with high-calorie and high-prote...Objective To investigate the effect of Yinlai Decoction(YD)on the microstructure of colon,and activity of D-lactic acid(DLA)and diamine oxidase(DAO)in serum of pneumonia mice model fed with high-calorie and high-protein diet(HCD).Methods Sixty male Kunming mice were randomly divided into 6 groups by the random number table method:normal control,pneumonia,HCD,HCD with pneumonia(HCD-P),YD(229.2 mg/mL),and dexamethasone(15.63 mg/mL)groups,with 10 in each group.HCD mice were fed with 52%milk solution by gavage.Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water,twice daily,for 3 days.After hematoxylin-eosin staining,the changes in the colon structure were observed under light microscopy and transmission electron microscope,respectively.Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.Results The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact.The colonic mucosal goblet cells in the pneumonia group tended to increase,and the size of the microvilli varied.In the HCD-P group,the mucosal goblet cells showed a marked increase in size with increased secretory activity.Loose mucosal epithelial connections were also observed,as shown by widened intercellular gaps with short sparse microvilli.These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment,while there was no significant improvement after dexamethasone treatment.The serum DLA level was significantly higher in the pneumonia,HCD,and HCD-P groups as compared with the normal control group(P<0.05).Serum DLA was significantly lower in the YD group than HCD-P group(P<0.05).Moreover,serum DLA level significantly increased in the dexamethasone group as compared with the YD group(P<0.01).There was no statistical significance in the serum level of DAO among groups(P>0.05).Conclusions YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure,thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.展开更多
基金supported by the National Natural Science Foundation of China(52273159,52273158,U21A2099,52173149,52073280,52022095,51973216,51873207,51833010)the Science and Technology Development Program of Jilin Province(20210509005RQ,20210504001GH,20200404182YY)+1 种基金the“Special Project for City-Academy Scientific and Technological Innovation Cooperation”of Changchun(21SH14)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019230)。
文摘Chiral materials with the same atomic compositions exhibit different chemical,physical,and biological properties because of their distinct spatial structures.Herein,a chiral strategy was proposed to develop poly(lactic acid)(PLA)nanoparticle as an efficient nanoadjuvant to activate adaptive anticancer immunity.Two chiral nanovaccines were prepared by directly mixing amino-terminated PLA(PLLA-NH2 or PDLA-NH2)with the model protein antigen ovalbumin(OVA).After being injected into mice subcutaneously,both nanovaccines efficiently migrated to the lymph nodes to initiate the sequential anticancer immune responses.Compared with the PLLA nanovaccine(PLLA-OVA),the PDLA one(PDLA-OVA)contributed to more robust dendritic cell(DC)maturation,antigen presentation,and T lymphocyte activation.In addition to the activation of cellular immunity,PDLA-OVA also triggered a more vigorous activation of humoral immunity,which induced the production of more anti-OVA immunoglobulin G(IgG)than PLLA-OVA.When used as prophylactic or therapeutic nanovaccine toward murine melanoma models,PDLA-OVA triggered more potent adaptive anticancer immune responses that more effectively inhibited the cancer genesis and progression,indicating the significant potential of immunologically effective PDLA nanoadjuvant in cancer immunotherapy.
基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202006)。
文摘Objective To investigate the effect of Yinlai Decoction(YD)on the microstructure of colon,and activity of D-lactic acid(DLA)and diamine oxidase(DAO)in serum of pneumonia mice model fed with high-calorie and high-protein diet(HCD).Methods Sixty male Kunming mice were randomly divided into 6 groups by the random number table method:normal control,pneumonia,HCD,HCD with pneumonia(HCD-P),YD(229.2 mg/mL),and dexamethasone(15.63 mg/mL)groups,with 10 in each group.HCD mice were fed with 52%milk solution by gavage.Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water,twice daily,for 3 days.After hematoxylin-eosin staining,the changes in the colon structure were observed under light microscopy and transmission electron microscope,respectively.Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.Results The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact.The colonic mucosal goblet cells in the pneumonia group tended to increase,and the size of the microvilli varied.In the HCD-P group,the mucosal goblet cells showed a marked increase in size with increased secretory activity.Loose mucosal epithelial connections were also observed,as shown by widened intercellular gaps with short sparse microvilli.These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment,while there was no significant improvement after dexamethasone treatment.The serum DLA level was significantly higher in the pneumonia,HCD,and HCD-P groups as compared with the normal control group(P<0.05).Serum DLA was significantly lower in the YD group than HCD-P group(P<0.05).Moreover,serum DLA level significantly increased in the dexamethasone group as compared with the YD group(P<0.01).There was no statistical significance in the serum level of DAO among groups(P>0.05).Conclusions YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure,thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
