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1.
Res Vet Sci ; 170: 105178, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402660

RESUMO

In pet clinics, the number of cases using trauma drugs accounts for >10% of the total number of cases, and most wounds are healing by second intention. The prolongation of wound healing time causes inconvenience and burden to pets and pet owners. Therefore, how to reduce wound healing time and achieve maximum recovery of tissue function and aesthetics is one of the focuses of veterinary clinical practice. Wound suppuration caused by Staphylococcus aureus and Pseudomonas aeruginosa is the main cause of delaying wound healing. Clinically, available antimicrobial treatments are almost exhausted due to the production of large numbers of resistant bacteria. At present, there are no bacteria resistant to traditional Chinese medicine (TCM), which makes TCM have the potential to become an effective drug for the treatment of bacterial infections, so the use of TCM in the treatment of traumatic infections has broad prospects. Based on the characteristics of infection syndrome, three different prescriptions were formulated in our laboratory, and the most effective prescription and dosage form was screened and named Lianrong Healing Cream (LRHC). The results showed that LRHC regulated the expression of fibroblast growth factor-2 (FGF-2), epidermal growth factor-1 (EGF-1), transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor-1 (VEGF-1) genes in wound tissues and fibroblasts, thereby accelerating wound healing and repairing wound appearance and function. The results of this study may be help to develop TCM formulation for traumatic infections.


Assuntos
Medicina Tradicional Chinesa , Cicatrização , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Epidérmico/farmacologia
2.
Poult Sci ; 102(10): 102992, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37595499

RESUMO

The modified rougan decoction (MRGD) compound formula has been proven a certain ability to relieve lipopolysaccharide-enrofloxacin (LPS-ENR)-induced liver oxidant injury in chickens. Recent advances have shown that mitochondrial dysfunction affects the development of many diseases, leading to increased interest in exploring its effects. Using LPS-ENR-injured in vivo and in vitro to further evaluate the effects of MRGD on mitochondrial structure and function, and emphasized further investigation of its molecular mechanism. After LPS-ENR treatment, the levels of inflammation and apoptosis markers were increased, along with higher mitochondrial injury. Results showed that MRGD reduced inflammatory factors expression and inhibited the nuclear translocation of NF-κB P65, reducing the inflammatory response in vivo and in vitro. Additionally, MRGD pretreatment inhibited mitochondrial dysfunction, mitochondrial oxidative stress, and mitochondrial pathway apoptosis by maintaining mitochondrial structure and function. Moreover, treatment with the inhibitor EX527 showed that MRGD promoted mitochondrial biogenesis ability through the SIRT1/PGC-1α pathway and interfered with mitochondrial dynamics, and activate Nrf2. In summary, MRGD played a key role in promoting mitochondrial function and thus alleviating hepatocyte apoptosis in vivo and in vitro at least in part.


Assuntos
Lipopolissacarídeos , Sirtuína 1 , Animais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Lipopolissacarídeos/farmacologia , Galinhas/metabolismo , Mitocôndrias/metabolismo , Apoptose , Transdução de Sinais , Hepatócitos/metabolismo , Estresse Oxidativo
3.
Int J Biol Macromol ; 245: 125419, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37364809

RESUMO

In order to ascertain the mechanism underlying the therapeutic efficacy of Bush sophora root polysaccharides (BSRPS) and phosphorylated Bush sophora root polysaccharides (pBSRPS) in the treatment of in duck viral hepatitis (DVH), an investigation was conducted to assess the protective impact of BSRPS and pBSRPS against duck hepatitis A virus type 1 (DHAV-1) induced mitochondrial dysfunction both in vivo and vitro. The BSRPS underwent modification through the utilization of the sodium trimetaphosphate - sodium tripolyphosphate method, and was subsequently characterized though Fourier infrared spectroscopy and scanning electron microscopy. Following this, the degree of mitochondrial oxidative damage and dysfunction was described through the use of fluorescence probes and various antioxidative enzyme assay kits. Furthermore, the utilization of transmission electron microscopy facilitated the observation of alterations in the mitochondrial ultrastructure within the liver tissue. Our findings demonstrated that both BSRPS and pBSRPS effectively mitigated mitochondrial oxidative stress and conserved mitochondrial functionality, as evidenced by heightened antioxidant enzyme activity, augmented ATP production, and stabilized mitochondrial membrane potential. Meanwhile, the histological and biochemical examinations revealed that the administration of BSRPS and pBSRPS resulted in a reduction of focal necrosis and infiltration of inflammatory cells, thereby mitigating liver injury. Additionally, both BSRPS and pBSRPS exhibited the ability to maintain liver mitochondrial membrane integrity and enhance the survival rate of ducklings infected with DHAV-1. Notably, pBSRPS demonstrated superior performance in all aspects of mitochondrial function compared to BSRPS. The findings indicated that maintaining mitochondrial homeostasis is a crucial factor in DHAV-1 infections, and the administration of BSRPS and pBSRPS may mitigate mitochondrial dysfunction and safeguard liver function.


Assuntos
Vírus da Hepatite do Pato , Hepatite Viral Animal , Hepatite Viral Humana , Infecções por Picornaviridae , Doenças das Aves Domésticas , Sophora , Animais , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/patologia , Patos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Sophora/química , Mitocôndrias , Polissacarídeos/química , Hepatite Viral Humana/tratamento farmacológico , Infecções por Picornaviridae/tratamento farmacológico , Infecções por Picornaviridae/patologia , Doenças das Aves Domésticas/tratamento farmacológico
4.
Vet Sci ; 10(5)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37235411

RESUMO

Escherichia coli is one of the most common pathogenic bacteria in diarrheal chickens, leading to serious economic losses in the poultry industry. The limited effect of antibiotics on antibiotic-resistant E. coli makes this bacterium a potential threat to human health. Yujin powder (YJP) has been reported as an agent that releases the symptoms caused by E. coli for a long time. The objective of this study is to investigate the effect of Yujin powder (YJP) and its components, Scutellariae Radix (SR) and Baicalin (Bac), anti-against multi-drug-resistant E. coli in vitro and in vivo. A multi-drug-resistant bacteria was isolated and identified from a clinical diarrheal chick. Then, the anti-bacterial effects of drugs were assessed in vitro and in vivo by analyzing the bacteria loads of organs, the levels of endotoxin, TNF-α, IL-1ß, and IL-6 of the serum. Results found that the pathogenic E. coli was resistant to 19 tested antibiotics. YJP, SR, and Bac could directly inhibit the growth of this strain at high concentrations in vitro, and presents obvious anti-bacterial effects by reducing the bacterial loads, the release of endotoxin, and inflammation in vivo, which was much more effective than the resistant antibiotic ciprofloxacin. This study demonstrates that those natural medicines have the potential to be used as novel treatments to treat the disease caused by this isolated MDREC strain.

5.
Poult Sci ; 102(3): 102404, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36584418

RESUMO

Liver injury plays a heavy burden on the chicken industry. Although modified rougan decoction is a prescription for the treatment of liver disease based on the classical prescription of rougan decoction (containing peony and licorice). However, the effect and mechanism of modified rougan decoction on the liver remain unclear. In this study, the effects of the water extracts (MRGD) and the alcohol precipitates of water extracts (MRGDE) against lipopolysaccharide-enrofloxacin (LPS-ENR)-induced hepatotoxicity were discussed in vivo and in vitro. The isolated hepatocytes and 128 one-day-old Hyline chickens were considered research objects. The indices of liver injury and oxidative stress were evaluated by hematoxylin and eosin (H&E) stained and the assay kits, and the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway was detected by the RT-PCR, western blot, and immunofluorescence tests. All data were analyzed using the IBM SPSS 20.0 software. In vivo, the structural integrity of the liver was maintained, AST, ALT, and MDA levels were decreased, and antioxidant enzymes were increased, confirming that the oxidative stress was reduced and liver injury was alleviated. Correspondingly, MRGD and MRGDE were observed to improve cell viability and decrease lactate dehydrogenase (LDH) in vitro, and the cell oxidative damage was reduced. In addition, the nuclear translocation of Nrf2 was improved significantly, and the mRNA and protein expression levels of the related genes were upregulated. In conclusion, MRGD and MRGDE can exert a protective effect against LPS-ENR-induced hepatotoxicity by activating the Nrf2/ARE pathway, which might be a potential therapeutic prescription for preventing or treating liver injury. Notably, no significant difference was found between the 2 extracts, suggesting that a depth extraction method did not always improve the efficacy of natural medicine. Our results provided new insights into finding effective hepatoprotective medicine.


Assuntos
Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas , Animais , Antioxidantes/metabolismo , Lipopolissacarídeos/toxicidade , Galinhas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Enrofloxacina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse Oxidativo , Fígado/metabolismo
6.
Vet Microbiol ; 275: 109600, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36395693

RESUMO

To define the underlying mechanism of the beneficial role of Chrysanthemum indicum polysaccharides (CIPS) and phosphorylated Chrysanthemum indicum polysaccharides (pCIPS) in duck viral hepatitis (DVH), we evaluated the protective effects of the CIPS and pCIPS against DVH in terms of antioxidation and mitochondrial function. Fluorescence probes and several assay kits were used to determine the oxidative stress and mitochondrial dysfunction in vitro and vivo. Additionally, transmission electron microscopy was applied to observe the changes of mitochondrial ultrastructure in the liver tissue. Our results indicate that the CIPS and pCIPS significantly enhanced the survival of duck hepatitis A virus type 1 (DHAV-1) infected ducklings. Moreover, the CIPS and pCIPS suppressed oxidative stress and preserved mitochondrial function, such as enhanced antioxidant enzyme activity, increased ATP production, and stabilized mitochondrial membrane potential (MMP). Meanwhile, the results of hematoxylin-eosin (HE) staining and serum biochemical examination demonstrated that treatment with the CIPS and pCIPS could decrease focal necrosis and infiltration of inflammatory cells, which in turn reducing liver injury. Furthermore, the CIPS and pCIPS were able to preserve liver mitochondrial membrane integrity in DHAV-1 challenged ducklings. Notably, the pCIPS was significantly outperformed the CIPS on all measures of liver and mitochondrial function. These results suggested that mitochondrial homeostasis plays an important role in alleviating oxidative damage in the livers, and the hepatocyte protective effects of the CIPS were enhanced after phosphorylation modification.


Assuntos
Infecções por Chlamydia , Chrysanthemum , Vírus da Hepatite do Pato , Hepatite Viral Humana , Animais , Patos , Mitocôndrias , Estresse Oxidativo , Polissacarídeos/farmacologia , Infecções por Chlamydia/veterinária , Antioxidantes
7.
Vet Res ; 53(1): 83, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224607

RESUMO

Staphylococcus saprophyticus is frequently involved in various difficult-to-treat infections due to the formation of biofilms. To identify useful antibiofilm strategies, this study explored the efficacy and mechanism of baicalin in enhancing the ability of azithromycin against multidrug-resistant Staphylococcus saprophyticus-Liu-2016-Liyang, China-francolin (MDRSS) biofilms in vitro and in vivo. When azithromycin was used in combination with baicalin, the minimum inhibitory concentration in biofilm (MICB) for azithromycin decreased 4- to 512-fold. Compared with the azithromycin and baicalin groups, the combination of azithromycin and baicalin could not reduce the biofilm biomass, but the dispersion rates of biofilm were decreased and the bactericidal ability was increased. Furthermore, the relative transcript levels of WalK/R system-related genes were upregulated by the addition of baicalin or azithromycin plus baicalin compared with that of the azithromycin and blank control groups. The strong correlation relationship between the WalK/R system and the bactericidal index demonstrated that baicalin enhanced the bactericidal effect of azithromycin on MDRSS biofilms by modulating the WalK/R system. In the mouse cutaneous infection model, the combination of azithromycin and baicalin succeeded in eradicating MDRSS and decreasing pathological injuries. This study indicated that baicalin has the potential to be an adjuvant to enhance the antimicrobial activity of azithromycin against MDRSS in the biofilm form by modulating the WalK/R system.


Assuntos
Azitromicina , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Azitromicina/farmacologia , Biofilmes , Camundongos , Testes de Sensibilidade Microbiana/veterinária , Staphylococcus saprophyticus
8.
Front Vet Sci ; 9: 827674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252422

RESUMO

In recent years, the efficacy of antibiotics has been threatened by the evolution of bacterial resistance. We previously demonstrated that baicalin (Bac) showed synergies with azithromycin (Azm) against Azm-resistant Staphylococcus saprophyticus (ARSS). The aim of this study was to explore the roles of Bac in reversing the resistance of ARSS to Azm. The ARSS was sequentially passaged for 20 days with the sub-MIC (minimum inhibitory concentration) of Bac. The strain that recovered sensitivity to Azm was named Azm-sensitive S. saprophyticus (ASSS). The sub-MIC of Bac reversed the resistance of ARSS to Azm. The MIC of Azm against the ASSS strain was 0.488 mg/l, and it was stable within 20 passages. The highest rate of resistance reversal reached 3.09% after ARSS was exposed to 31.25 mg/l Bac for 20 days. Furthermore, semiquantitative biofilm and RT-PCR assays reflected that the ability of biofilm formation and the transcript levels of msrA, mphC, and virulence-associated genes in the ASSS strain were significantly lower than those of the ARSS strain (p < 0.05). Simultaneously, Azm delayed the start time of death, alleviated the injury of the kidney, and decreased the bacterial burden in organs and cytokine levels in mice infected with ASSS. In contrast, Azm did not have a good therapeutic effect on mice infected with ARSS. Therefore, Bac has the potential to be an agent that reversed the resistance of ARSS to Azm.

9.
Res Vet Sci ; 141: 156-163, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34749100

RESUMO

Duck hepatitis A virus type 1 (DHAV-1) infection is the main cause of duck viral hepatitis, but the replication process and distribution of DHAV-1 in vivo are still poorly understood. In this study, six-day-old ducklings were infected by two different methods: by intramuscular injection to establish DHAV-1 infection animal models and by the combined administration of virus solution orally, through nasal inhalation, through inoculation of the eye, and through intrarectal contact to simulate natural infection. Tissues were collected at different time points and quantitative real-time polymerase chain reaction (qPCR) was employed to analyze the gene expression levels of DHAV-1 in different tissues. The results showed that the viral gene levels responded to the different challenge methods. Viral gene expression levels in all tissues in the intramuscular injection group were lower than those in the group that simulated natural infection. In both groups, the liver was the primary tissue that responsible for the replication of DHAV-1 genes, as virus gene level peaked at 4 h post infection (hpi). In addition, the respiratory and digestive tracts were important regions for DHAV-1 infection as high viral gene levels were detected at early (8 hpi) and late (96 hpi) stages of infection. This research utilized a novel infection method to simulate natural infection and analyzed the DHAV-1 distribution in different tissues. The findings can provide guidance for making prevention and control measures.


Assuntos
Vírus da Hepatite do Pato , Hepatite Viral Animal , Infecções por Picornaviridae , Doenças das Aves Domésticas , Animais , Patos , Infecções por Picornaviridae/veterinária
10.
Vet Microbiol ; 262: 109242, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34562786

RESUMO

The ability to form biofilms on surfaces makes Staphylococcus saprophyticus (S. saprophyticus) becomes the main pathogenic factor in nosocomial infections. Previously, we demonstrated that baicalin (Bac) inhibited azithromycin-resistant S. saprophyticus (ARSS) biofilm formation. This investigation aims to explore the influence of baicalin on primary adhesion and aggregation phases of biofilm formation, and the treatment effect of baicalin and azithromycin on ARSS biofilm-associated infection. Crystal violet (CV) staining and scanning electron microscope (SEM) observations clearly showed that sub-inhibitory concentration baicalin inhibited ARSS biofilm formation when baicalin was added before the adhesion and aggregation phases. Baicalin significantly increased the relative adhesion inhibition rate and decreased the rate of bacteria aggregation in a dose-dependent manner. Moreover, CLSM and cell lysis assays revealed that baicalin inhibited the production of surface proteins and cell autolysis in bacteria adhesion and aggregation phases of biofilm formation. Meanwhile, the relative expressions of adhesion-related and autolysis-related genes were down-regulated by baicalin. In vivo, the combination of baicalin and azithromycin succeeded in eradicating ARSS from the mouse cutaneous infection model and decreasing the pathological injuries, the expressions of cytokines in infected tissue, and the number of inflammatory cells in the blood. Simultaneously, baicalin decreased the bacterial burdens in tubes, the level of TNF-α, and the number of monocytes and neutrophils compared with that of the SS and azithromycin groups. Based on these results, baicalin inhibited the adhesion and aggregation phases of biofilm formation by influenced the production of surface proteins and cell autolysis. Baicalin and azithromycin synergetically treated ARSS biofilm-associated infection.


Assuntos
Azitromicina , Aderência Bacteriana , Flavonoides , Staphylococcus saprophyticus , Animais , Aderência Bacteriana/efeitos dos fármacos , Biofilmes , Flavonoides/farmacologia , Proteínas de Membrana/metabolismo , Camundongos , Staphylococcus saprophyticus/efeitos dos fármacos
11.
Colloids Surf B Biointerfaces ; 204: 111799, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33971614

RESUMO

Nanoparticle delivery of functional molecules and vaccine is a promising method for enhancing the immune response. The objective of this study was to design chitosan (CS)-modified ginseng stem-leaf saponins (GSLS)-encapsulated cubosomes (Cub-GSLSCS) as a vaccine delivery system and explore its immunologic activity and adjuvanticity. In this study, CS-modified GSLS-encapsulated cubosomes (Cub-GSLSCS) were prepared. The storage stability of GSLS and that of ovalbumin (OVA) were measured. Additionally, the immunopotentiation of Cub-GSLSCS were assessed on potentiating macrophage in vitro, and the adjuvant activity was evaluated through immune response triggered by OVA model antigen. The encapsulation efficiency of optimized Cub-GSLSCS was about 65 % with Im3m nanostructure. The Cub-GSLSCS showed excellent stability and sustained release for up to 28 days. In vitro, Cub-GSLSCS nanoparticles improved cellular uptake, stimulated cytokines secretion of IL-6, IL-12, TNF-α, and generated more inducible nitric oxide synthase (iNOS) to produce higher levels of nitric oxide (NO) compared with other groups. Furthermore, the immunoadjuvant effects of OVA encapsulated Cub-GSLSCS nanoparticles (Cub-GSLSCS-OVA) were observed through immunized mice. Results showed that the ratio of CD4+/CD8 + T lymphocytes was increased in Cub-GSLSCS-OVA group. In addition, Cub-GSLSCS-OVA nanoparticles induced dramatically high OVA-specific IgG, IgG1, and IgG2a levels and stimulated the secretion of cytokines. Cub-GSLSCS may be a potential vaccine delivery system and induce a long-term sustained immunogenicity.


Assuntos
Quitosana , Nanopartículas , Panax , Saponinas , Adjuvantes Imunológicos/farmacologia , Animais , Camundongos , Ovalbumina , Folhas de Planta , Saponinas/farmacologia
12.
Poult Sci ; 100(5): 101032, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33744612

RESUMO

Duck hepatitis A virus type 1 (DHAV-1) is the main pathogen of duck viral hepatitis, but the efficacy of the licensed commercial vaccine needs to be further improved. Therapeutic measures of specific drugs for DHAV-1-infected ducklings need to be urgently developed. Baicalin possesses good antiviral effects. This study aims to investigate the mechanism of baicalin in protecting hepatic mitochondrial function from DHAV-1. The ELISA method was used to detect changes of hepatic and mitochondrial catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), inducible nitric oxide synthase (iNOS), adenosine triphosphate (ATP), and malondialdehyde (MDA) levels in vivo and vitro. Hematoxylin and eosin sections and transmission electron microscopy were used to observe liver pathological changes and mitochondrial structural changes. The changes in mitochondrial membrane potential were detected by JC-1 staining method. Western blot and quantitative real-time PCR were employed to analyze the gene and protein expressions in the nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway in duck embryonic hepatocytes infected with DHAV-1. Results showed the administration of baicalin increased the survival rate of ducklings, and alleviated hepatic damage caused by DHAV-1 by enhancing the antioxidant enzyme activities of the liver and mitochondria, including SOD, GPX, CAT, and reducing lipid peroxidative damage (MDA content) and iNOS activities. The mitochondrial ultrastructure changed and the significant increase of ATP content showed that baicalin maintained the structural integrity and ameliorated mitochondrial dysfunction after DHAV-1 infection. In vitro, DHAV-1 infection led to loss of mitochondrial membrane potential and lipid peroxidation and decreased antioxidative enzyme activities (SOD, GPX) and mitochondrial respiratory chain complex activities (succinate dehydrogenase, cytochrome c oxidase). Baicalin relieved the above changes caused by DHAV-1 and activated the gene and protein expressions of Nrf2, which activated ARE-dependent genes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1), SOD-1, and GPX-1. In addition, baicalin increased the protein expressions of antioxidative enzymes (SOD, GPX). Hence, baicalin protects the liver against oxidative stress in hepatic mitochondria caused by DHAV-1 via activating the Nrf2/ARE signaling pathway.


Assuntos
Vírus da Hepatite do Pato , Animais , Antioxidantes/metabolismo , Galinhas/metabolismo , Patos/metabolismo , Flavonoides , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais
13.
Int J Nanomedicine ; 15: 5527-5543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848386

RESUMO

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) has been extensively applied for sustained drug delivery and vaccine delivery system. However, vaccines delivered by PLGA nanoparticles alone could not effectively activate antigen-presenting cells (APCs) to induce strong immune responses. PURPOSE: The aim of the present study was to design polyethylenimine (PEI)-modified Chinese yam polysaccharide (CYP)-encapsulated PLGA nanoparticles (CYPP-PEI) as a vaccine delivery system and evaluate the adjuvant activities in vitro and in vivo. MATERIALS AND METHODS: Cationic-modified nanoparticles exhibited high antigen absorption and could be efficiently taken by APCs to enhance the immune responses. Therefore, PEI-modified CYP-encapsulated PLGA nanoparticles (CYPP-PEI) were prepared. The storage stability and effective adsorption capacity for porcine circovirus-2 (PCV-2) antigen of these antigen-absorbed nanoparticles were measured for one month. Furthermore, the adjuvant activity of CYPP-PEI nanoparticles was evaluated on macrophages in vitro and through immune responses triggered by PCV-2 antigen in vivo. RESULTS: The PCV-2 absorbed CYPP-PEI nanoparticles showed excellent storage stability and high absorption efficiency of PCV-2 antigen. In vitro, CYPP-PEI nanoparticles promoted antigen uptake, enhanced surface molecular expressions of CD80 and CD86, and improved cytokine secretion of TNF-α, IFN-γ, and IL-12p70 in macrophages. After immunization with CYPP-PEI/PCV-2 formulation in mice, the expressions of surface activation markers on dendritic cells which located in draining lymph nodes were increased, such as MHCI, MHCII, and CD80. In addition, CYPP-PEI nanoparticles induced dramatically high PCV-2-specific IgG levels which could last for a long time and stimulated the secretion of subtype antibodies and cytokines. The results showed that CYPP-PEI could induce Th1/Th2 mixed but Th1-biased type immune responses. CONCLUSION: Polyethylenimine-modified Chinese yam polysaccharide-encapsulated PLGA nanoparticle was a potential vaccine delivery system to trigger strong and persistent immune responses.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Dioscorea/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Polissacarídeos/química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Antígenos/farmacologia , Circovirus/imunologia , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Estabilidade de Medicamentos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos ICR , Nanopartículas/administração & dosagem , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Vacinas/administração & dosagem , Vacinas/imunologia
14.
Int J Biol Macromol ; 148: 793-801, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972196

RESUMO

Recently, the cubosomes have been widely studied as drug carriers. It has been described that cubosomes could further stimulate the immune response after carrying the immune enhancer. Polygonatum sibiricum polysaccharide (PSP), one of the most important biologically active ingredients of Polygonatum sibiricum, has been reported as an immunostimulant to improve immune responses. This study was aimed to observe the immunomodulation effects of ovalbumin (OVA) absorbed cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs/OVA). Firstly, the antigen uptake of CTAB-modified PSP-Cubs/OVA by macrophages was determined in vitro. After that, mice were immunized with CTAB-modified PSP-Cubs/OVA. The activation of dendritic cells in lymph nodes, activation of lymphocyte, ratios of CD4+ to CD8+, the concentrations of OVA-specific IgG in serum and the cytokines concentrations were analyzed. As the results showed, CTAB-modified PSP-Cubs/OVA could promote the production of OVA-specific IgG in serum. The ratio of CD4+ to CD8+ in CTAB-modified PSP-Cubs/OVA group was significantly increased compared with other groups. CTAB-modified PSP-Cubs/OVA could significantly activate dendritic cells and promote lymphocyte proliferation. The results indicated that CTAB-modified PSP-Cubs/OVA could promote the secretion of related cytokines and the proliferation of lymphocytes, stimulate the cellular immune response and increase the level of humoral immunity. Above all, CTAB-modified PSP-Cubs had good adjuvant activity.


Assuntos
Adjuvantes Imunológicos/farmacologia , Cetrimônio/imunologia , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Ovalbumina/imunologia , Polygonatum/imunologia , Polissacarídeos/farmacologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Células Dendríticas/imunologia , Imunomodulação/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos ICR
15.
Int J Biol Macromol ; 141: 1158-1164, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520706

RESUMO

Ganoderma lucidum has been widely used as a fungal, for promoting health and longevity in China and other Asian countries. Polysaccharide (PS) extracted from Ganoderma lucidum exhibits a variety of immunomodulatory activities and has the ability to induce strong immune responses. Liposomes (Lip) have been shown to be useful carriers of vaccine antigens and can be applied as a versatile delivery system for vaccine adjuvants. Here, PS and inactivated porcine circovirus type II (PCV-II) were encapsulated into Lip as a vaccine and inoculated into mice. The magnitude and kinetics of adjuvant activity were investigated. Polysaccharide-loaded liposomes (Lip-PS) could induce more efficient PCV-II-specific immune responses than other single-component formulations. The Lip-PS group displayed robust and higher titers of PCV-II-specific immunoglobulin (Ig)G antibodies and IgG subtypes as well as higher cytokine levels, furthermore, splenocytes were activated by Lip-PS. Thus, Lip-PS formulation produced vigorous humoral and cellular immune responses, with a mixed T-helper (Th)1/Th2/Th17 immune response and slight Th1 polarized cellular immune response. Overall, these results suggested that Lip-PS could provide a universal platform for vaccine design against PCV-II.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Circovirus/imunologia , Polissacarídeos Fúngicos/farmacologia , Ganoderma/química , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Feminino , Imunoglobulina G/imunologia , Lipossomos , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia
16.
Carbohydr Polym ; 211: 217-226, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824082

RESUMO

Alhagi honey polysaccharides (AHP) have been widely studied as immunomodulators. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles have been frequently used to control the release of drugs. In this study, AHP was extracted and encapsulated within PLGA (AHPP). Enhancement of immune activity in vitro and the adjuvanticity when inoculated with OVA were evaluated. The results demonstrated that the average molecular weight of AHP was 46.8 kDa and possessed typical polysaccharide absorption peaks. The entrapment efficiency for AHP within AHPP was 65.76 ± 3.31%. AHPP significantly stimulated phagocytic activity, MHCII and CD86 expression in macrophages. Further investigation showed that AHPP/OVA significantly enhanced lymphocyte proliferation and improved the CD4+/CD8+ T cell ratio. Moreover, AHPP/OVA treatment significantly increased IgG levels and up-regulated Th-associated cytokines with overall Th1 polarization. These studies demonstrated that AHP encapsulated within PLGA as a vaccine delivery system enhanced adaptive immunity.


Assuntos
Mel , Fatores Imunológicos/administração & dosagem , Nanopartículas/administração & dosagem , Ovalbumina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Sistemas de Liberação de Medicamentos , Linfócitos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/fisiologia , Camundongos Endogâmicos ICR , Fagocitose/efeitos dos fármacos , Vacinas/administração & dosagem
17.
Int J Pharm ; 559: 410-419, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30738129

RESUMO

This study aimed to optimize the preparation conditions for cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs) by response surface methodology (RSM). Glyceryl-monooleate (GMO) was used as the lipid base for the cubosomes. The optimal preparation conditions of CTAB-modified PSP-Cubs were as follows: the mass percentage of PSP to GMO (X1), Poloxamer 407 (F127) to GMO (X2) and water to GMO (X3) was 1.4%, 9% and 50%, respectively. The encapsulation efficiency (EE) of CTAB-modified PSP-Cubs under the experimental conditions was 62.4 ±â€¯3.6%, which was close to our predicted value. The particle size, polydispersity index (PDI) and zeta potential of CTAB-modified PSP-Cubs were 427.7 ±â€¯8.0 nm, 0.236 ±â€¯0.024 and 19.2 ±â€¯0.4 mV, respectively. Specific modifications were able to slow down in vitro release behaviors and reduce cytotoxicity to some extent. The effects of CTAB-modified PSP-Cubs on splenic lymphocytes were also investigated. When splenic lymphocytes were treated with CTAB-modified PSP-Cubs together with LPS or PHA, the results showed more favorable effects on cellular proliferation than blank cubosomes or free PSP at certain concentrations.


Assuntos
Cetrimônio/química , Cetrimônio/farmacologia , Linfócitos/efeitos dos fármacos , Polygonatum/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Baço/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Glicerídeos/química , Glicerídeos/farmacologia , Camundongos , Tamanho da Partícula , Poloxâmero/química
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