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1.
Int J Biol Macromol ; 262(Pt 2): 129982, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354941

RESUMO

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.


Assuntos
Cistanche , Vacinas , Animais , Camundongos , Adjuvantes de Vacinas , Dióxido de Silício , Mucosa , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Polissacarídeos/farmacologia , Imunidade nas Mucosas
3.
Mil Med Res ; 9(1): 27, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35681166

RESUMO

Since its establishment in 2014, Military Medical Research has come a long way in becoming a premier journal for scientific articles from various different specialties, with a special emphasis on topics with military relevance. The field of military medicine may be obscure, and may not be readily encountered by the typical clinician on a day-to-day basis. This journal aims not only to pursue excellence in military research, but also keep current with the latest advancements on general medical topics from each and every specialty. This editorial serves to recap and synthesize the existing progress, updates and future needs of military medical excellence, discussing foremostly the unique traits of literature published in this journal, and subsequently presenting the discourse regarding wartime and peacetime medicine, the role of the military in a public health emergency, as well as wound healing and organ regeneration. Special attention have been devoted to military topics to shed light on the effects of Chemical, Biological, Radiological and Explosive (CBRE) warfare, environmental medicine and military psychiatry, topics which rarely have a chance to be discussed elsewhere. The interconnectedness between military combat and soldier physical and mental well-being is intricate, and has been distorted by pandemics such as coronavirus disease 2019 (COVID-19). This journal has come a long way since its first article was published, steadily contributing to the existing knowledge pool on general medical topics with a military slant. Only with continuous research and sharing, can we build upon the work of the scientific community, with hopes for the betterment of patient care.


Assuntos
COVID-19 , Medicina Militar , Militares , Humanos , Pandemias , Publicações
4.
Phytomedicine ; 103: 154232, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35675749

RESUMO

BACKGROUND: It remains a huge challenge to recover the intestine immune function for the treatment of intestinal mucosal damage from chemotherapy with cyclophosphamide (CY). Alhagi honey polysaccharide (AH) has immunomodulation pharmacological activity, but the effect and mechanism on the intestinal immune system of CY-mice remain unclear. PURPOSE: In this experiment, the immunomodulatory activity of AH on intestinal immune in CY-mice and its mechanism of regulating the intestinal immune system was investigated. STUDY DESIGN AND METHODS: The experiment studied the immunomodulatory activity of AH on the intestinal immune system and its mechanism for the first time from in vitro and in vivo experiments. We investigated the immunomodulatory effects of AH on Caco-2 and dendritic cells (DCs) in vitro by using western blot (WB), flow cytometry, quantitative real-time PCR (qPCR), and ELISA methods. In vivo experiment, the immunosuppressive mouse model was established through being given intraperitoneal injection with CY (80 mg/kg) for 3 days. Then, mice oral administration of 800 mg/kg AH and 40 mg/kg levamisole hydrochloride for a week. Immunofluorescence, flow cytometry, ELISA, qPCR and WB were applied to examine the immunomodulatory activity of AH on the intestinal immune function of CY-mice, as well as the function of AH on the concentration of SCFAs in cecum by Gas chromatographic analysis. RESULTS: In vitro experiments, AH could significantly stimulate the expression of pIgR protein in Caco-2. It could also induce the DCs maturation and release the cytokines to regulate the immune response. In vivo experiments, AH could remarkably stimulate the DCs maturation and secrete more CCL20 to recruit DCs, then induce the T (CD4+ and CD8+) and B cells proliferation and activation. Moreover, it could further induce T helper cells to differentiate and secrete cytokines to enhance the secretion of sIgA. Furthermore, it also directly activated DCs and released cytokines to increase the content of pIgR, J-chain, and IgA+ cells in intestine, thereby enhancing the secretion of sIgA to protect the intestine. In addition, AH could obviously strengthen the SCFAs production in cecum to regulate the intestinal immune dysfunction induced by CY. CONCLUSION: In summary, oral administrated AH exhibits great benefits for treating CY-induced intestinal immunosuppression, and the mechanism of action mainly involves sIgA, DCs, SCFAs.


Assuntos
Mel , Enteropatias , Animais , Células CACO-2 , Ciclofosfamida/farmacologia , Citocinas/metabolismo , Células Dendríticas , Humanos , Imunoglobulina A Secretora , Intestinos , Camundongos , Polissacarídeos/farmacologia
5.
J Formos Med Assoc ; 121(12): 2465-2480, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35623930

RESUMO

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.


Assuntos
Artemisia , Rinite Alérgica , Humanos , Alérgenos , Pólen/efeitos adversos , Rinite Alérgica/terapia , Rinite Alérgica/etiologia , Taurina , Metabolômica , Imunoterapia , Resultado do Tratamento , Dessensibilização Imunológica/efeitos adversos
6.
Food Funct ; 12(20): 9693-9707, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664596

RESUMO

Alhagi honey polysaccharides (AH), a main active component of Alhagi honey, are known to possess excellent pharmacological activities and have been widely used as dietary supplements in traditional Chinese medicine for thousands of years. This study is aimed to investigate the heath effect of AH on murine intestinal mucosal immune function and composition of the gut microbiome. ICR mice received daily intragastric administration of AH (three dosages, 200 mg kg-1, 400 mg kg-1, and 800 mg kg-1) or saline for 7 consecutive days. Results indicated an improvement in the intestinal barrier function through increases in secretory immunoglobulin A (sIgA) and ß-defensins. Simultaneously, AH also significantly stimulated IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α cytokine secretion as compared to the control samples. Moreover, hematoxylin and eosin staining showed that AH enhanced the number of intraepithelial lymphocytes (IELs) in the small intestine. An obvious increase in the ratio of IgA+ cells of AH-treatment samples in the lamina propria was also detected by immunohistochemical staining. In addition, the CD3+, CD4+ and CD8+ T-cell ratio in mesenteric lymph nodes and Peyer's patches in the AH-treatment was significantly higher than that in the control group. Furthermore, 16S rDNA gene sequencing was used to monitor the dynamic changes in the gut microbiota. The result revealed that AH significantly increased the indexes of Shannon and obviously decreased the indexes of Simpson, suggesting the enhancement of the diversity and richness of the intestinal microbiome. Moreover, AH modulated the gut microbiome via increasing the abundance of probiotics and decreasing the levels of pathogenic bacteria. In summary, these results indicated that AH could be used as a prebiotic to enhance murine intestinal mucosal immunity and to modulate the gut microbiome.


Assuntos
Suplementos Nutricionais , Alimento Funcional , Mel , Imunidade nas Mucosas/efeitos dos fármacos , Polissacarídeos/farmacologia , Prebióticos , Administração Oral , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Polissacarídeos/administração & dosagem , Distribuição Aleatória , Organismos Livres de Patógenos Específicos
7.
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
8.
Front Immunol ; 11: 559746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329520

RESUMO

Background: Allergic rhinitis is a common disorder that affects 10% to 40% of the population worldwide. Allergen immunotherapy (AIT) represents the only therapy that has the potential to resolve clinical symptoms of allergic rhinitis. However, up to 30% of patients do not respond to AIT. Biomarkers predicting the clinical efficacy of AIT as early as possible would significantly improve the patient selection and reduce unnecessary societal costs. Methods: Artemisia pollen allergic patients who received at least 1-year AIT were enrolled. Clinical responses before and after 1-year AIT were evaluated to determine AIT responders. Artemisia specific IgE and IgG4 levels were measured by using ImmunoCAP and enzyme-linked immunosorbent assay (ELISA) separately. Stepwise regression analysis was performed to identify which rhinitis-relevant parameters explained the most variability in AIT results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics was applied to identify the potential candidate biomarkers in the sera of responders and non-responders collected before and after 1-year therapy. The diagnostic performance of the potential biomarkers was then assessed using enzyme-linked immunosorbent assay (ELISA) in 30 responders and 15 non-responders. Results: Artemisia specific IgE and IgG4 levels were elevated only in the responders. Regression analysis of allergic rhinitis-relevant parameters provided a robust model that included two most significant variables (sneeze and nasal congestion). Thirteen candidate biomarkers were identified for predicting AIT outcomes. Based on their association with allergy and protein fold change (more than 1.1 or less than 0.9), four proteins were identified to be potential biomarkers for predicting effective AIT. However, further ELISA revealed that only leukotriene A4 hydrolase (LTA4H) was consistent with the proteomics data. The LTA4H level in responders increased significantly (P < 0.001) after 1-year therapy, while that of non-responders remained unchanged. Assessment of LTA4H generated area under curve (AUC) value of 0.844 (95% confidence interval: 0.727 to 0.962; P < 0.05) in distinguishing responders from the non-responders, suggesting that serum LTA4H might be a potential biomarker for predicting the efficiency of AIT. Conclusion: Serum LTA4H may be a potential biomarker for early prediction of an effective AIT.


Assuntos
Biomarcadores , Dessensibilização Imunológica , Epóxido Hidrolases/sangue , Adolescente , Adulto , Alérgenos/imunologia , Criança , Cromatografia Líquida , Tomada de Decisão Clínica , Dessensibilização Imunológica/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Prognóstico , Proteômica/métodos , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/terapia , Espectrometria de Massas em Tandem , Resultado do Tratamento , Fluxo de Trabalho , Adulto Jovem
9.
Int J Biol Macromol ; 163: 1384-1392, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758599

RESUMO

In recent years, the high prevalence of avian influenza viruses especially H5N1 subtype isolated from poultry and human has become a major public health concern. Vaccination is still a major strategy for preventing H5N1 infections. Lentinan (LNT), a ß-1,3-glucohexaose with ß-1,6-branches, is extracted from Lentinus edodes and has been extensively studied for its immunoenhancement effects. In this study, we synthesized and characterized calcium carbonate (CaCO3) microparticles which modified with LNT as an adjuvant for H5N1 vaccine and investigated their ability to enhance immune responses. We prepared spherical and uniform CaCO3-LNT microparticles with a mean hydrodynamic size was around 2 µm. The H5N1 antigen-loaded CaCO3-LNT particles were injected into mice to evaluate their effectiveness as an adjuvant for H5N1 vaccines. The results demonstrated that CaCO3-LNT/H5N1 significantly enhanced the expression of MHC-II and CD86 in lymph node dendritic cells, and increased the ratio of CD4+ to CD8+ T cells in lymphocytes. Moreover, CaCO3-LNT/H5N1 surprisingly increased the HI titers and induced the secretion of IgG subtypes (IgG1 and IgG2b) and Th-associated cytokines (TNF-α, IFN-γ and IL-4) in immunized mice. Therefore, by combining with the immunostimulatory activity of LNT and the drug/antigen delivery capabilities of CaCO3, the CaCO3-LNT/H5N1 could induce a stronger cellular and humoral immune response and could be a potential adjuvant for the H5N1 vaccine.


Assuntos
Carbonato de Cálcio/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Lentinano/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Feminino , Imunidade/imunologia , Imunoglobulina G/imunologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos ICR , Vacinação/métodos
10.
Carbohydr Polym ; 245: 116520, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32718625

RESUMO

Adjuvants improve vaccine potency by enhancing immunogenicity and sustaining long-term immune responses. Lentinan (LNT), a ß-1,3-glucohexaose with ß-1,6-branches, is extracted from the mushroom Lentinus edodes and functions as an effective immunostimulatory drug. Previous studies have demonstrated the adjuvant activity of calcium carbonate (CaCO3) microspheres as well as their use as antigen delivery systems. In this study, we successfully loaded CaCO3 microspheres with LNT and evaluated their physicochemical characteristics prior to the adsorption of ovalbumin. Our experimental results demonstrated that LNT-CaCO3 significantly enhanced lymphocyte proliferation, and boosted the frequency of CD69 + B cells and the ratio of CD4+ to CD8 + T cells in spleen lymphocytes. Moreover, LNT-CaCO3 unexpectedly induced the secretion of IgG and Th-associated cytokines (IL-2, IL-4, IFN-γ, and TNF-α) in immunized mice. Therefore, LNT-CaCO3 microspheres induce robust cellular and humoral immune responses and have potential utility as vaccine delivery systems.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Carbonato de Cálcio/administração & dosagem , Lentinano/administração & dosagem , Microesferas , Vacinação/métodos , Vacinas/administração & dosagem , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral/efeitos dos fármacos , Imunogenicidade da Vacina , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Cogumelos Shiitake/química , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Vacinas/imunologia
11.
BMC Vet Res ; 15(1): 134, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064364

RESUMO

BACKGROUND: Duck viral hepatitis (DVH) is an acute disease of young ducklings with no effective veterinary drugs for treatment. Gynostemma pentaphyllum is a well-known traditional Chinese medicine that plays an important role in the treatment of various diseases. Gypenoside (GP), one of the main ingredients of Gynostemma pentaphyllum, was reported with good hepatoprotective effects. However, its low solubility limits its application in the clinics. To improve its solubility and bioactivity, a phosphorylated derivative of gypenoside (pGP) was prepared by the sodium trimetaphosphate-sodium tripolyphosphate (STMP-STPP) method. An infrared spectroscopy method was applied to analyse the structures of GP and pGP. Then, a methyl thiazolyl tetrazolium (MTT) colorimetric assay was applied to study the hepatocyte protective efficacy of these two drugs against duck hepatitis A virus type 1 (DHAV-1) infection, and qPCR, TUNEL labelling and flow cytometry methods were used to study the relevant hepatocyte protective in vitro. RESULTS: The infrared spectroscopy detection results showed that the phosphorylation modification of GP was successful. The MTT colorimetric assay results showed that both GP and pGP possessed good hepatocyte protective efficacy in vitro, and pGP performed better than GP when the drug was added before or after virus inoculation. Furthermore, the qPCR results revealed that both drugs could effectively inhibit the adsorption (when adding GP and pGP pre-virus inoculation), replication and release of DHAV-1, and the viral inhibition rate of pGP was greater than that of GP. The subsequent TUNEL labelling and flow cytometry assays showed that both GP and pGP could significantly inhibit duck embryo hepatocyte apoptosis induced by DHAV-1, and the inhibition effect of pGP was much stronger than that of GP. CONCLUSIONS: GP exerts good hepatocyte protective efficacy not only by inhibiting the proliferation of DHAV-1 but also by inhibiting duck embryonic hepatocyte apoptosis induced by DHAV-1, and phosphorylation modification significantly improves the antiviral and the anti-apoptotic effects of GP. Therefore, pGP has the potential to be developed into a novel drug against DHAV-1 infection.


Assuntos
Vírus da Hepatite do Pato/efeitos dos fármacos , Animais , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Patos , Gynostemma/química , Hepatite Viral Animal/tratamento farmacológico , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Fosforilação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Replicação Viral/efeitos dos fármacos
12.
Curr Mol Med ; 19(5): 376-386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30950349

RESUMO

BACKGROUND: Duck virus hepatitis (DVH) caused by duck hepatitis A virus type 1 (DHAV-1) is a malignant disease in ducklings, causing economic losses in the duck industry. However, there is still no antiviral drug against DHAV-1 in the clinic. OBJECTIVE: Our aim is to investigate the anti-DHAV-1 effect of baicalin, which is a flavonoid derived from the Chinese medicinal herb huangqin (Scutellaria baicalensis Georgi). METHODS: Here, we first detected its anti-DHAV-1 ability in vitro and in vivo. At the same time, the inhibition of baicalin on DHAV-1 reproduction was determined. Finally, we tested and verified the anti-oxidative and immuno-enhancing roles of baicalin on its curative effect on DVH. RESULTS: Baicalin possessed anti-DHAV-1 effect. It improved the cytoactive of DEH which was infected by DHAV-1 as well as reduced the DHAV-1 reproduction in DEH. Under baicalin treatment, mortality of ducklings infected by DHAV-1 decreased, additionally the DHAV-1 level and liver injury in such ducklings were significantly reduced or alleviated. The in vitro mechanism study indicated baicalin inhibited DHAV-1 reproduction via interfering the viral replication and release. Furthermore, the in vivo mechanism study manifested both the anti-oxidative and immuno-enhancing abilities of baicalin, which played crucial roles in its curative effect on DVH. CONCLUSION: This study may provide a scientific basis for developing baicalin as one or a part of the anti-DHAV-1 drugs.


Assuntos
Antivirais/farmacologia , Flavonoides/farmacologia , Vírus da Hepatite do Pato/efeitos dos fármacos , Hepatite Viral Animal/virologia , Animais , Antioxidantes/farmacologia , Células Cultivadas , Patos , Vírus da Hepatite do Pato/genética , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/mortalidade , Hepatite Viral Animal/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Testes de Função Hepática , Extratos Vegetais , Scutellaria baicalensis , Liberação de Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
13.
Carbohydr Polym ; 205: 540-549, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446138

RESUMO

Dendritic cells (DCs) are professional antigen-presenting cells (APC) that play a central role in the initiation and regulation of immune responses. We have previously demonstrated that Lycium barbarum polysaccharides liposomes (LBPL) as immune adjuvant elicits strong antigen-specific Th1 immune responses. The purpose of this study was to investigate underlying mechanism of liposomes promoting effect of Lycium barbarum polysaccharides (LBP) on activating DCs. LBP were loaded with high entrapment efficiency (86%) into liposomes using reverse phase evaporation. LBPL activation of phenotypic and functional maturation of DCs was explored through mechanistic studies of the TLR4-MyD88-NF-κB signaling pathway and amount of proinflammatory cytokines released. We found that LBPL indeed activated immature DCs and induced DCs maturation characterized by up-regulation of co-stimulatory molecules (MHCII, CD80, CD86), production of cytokines (IL-12p40, TNF-α), and enhancement of antigen uptake. Additionally, we demonstrated that liposomes could promote LBP up-regulation of TLR4, MyD88, TRAF6, NF-κB gene and protein expression.


Assuntos
Células Dendríticas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Lipossomos/farmacologia , Lycium/química , Polissacarídeos/farmacologia , Animais , Células da Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/metabolismo , Medicamentos de Ervas Chinesas/química , Feminino , Subunidade p40 da Interleucina-12/metabolismo , Lipossomos/química , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Polissacarídeos/química , Transdução de Sinais/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
14.
Int J Biol Macromol ; 109: 748-760, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29157913

RESUMO

Cubosomes, as biocompatible carriers in drug delivery systems, consist of curved bicontinuous lipid bilayers. With a honeycombed structure divided into two internal aqueous channels, cubosomes could be used for many bioactive ingredients. Achyranthes bidentata polysaccharides (ABPs) are isolated from the roots of Achyranthes bidentata, used in Chinese herbal medicine, and present a noticeable effect as an immunomodulator. This study investigates the optimal preparation of combined cubosome-ABP (Cub-ABP) nanoparticles using response surface methodology and explores their characteristics and stability. The encapsulation efficiency of optimized Cub-ABPs was 72.59%. In-vitro stability studies demonstrated the stability of Cub-ABPs and cubosome nanoparticles without ABPs; both were stable for up to 25days. Safe concentrations of Cub-ABPs and cubosome nanoparticles without ABPs are 104.06µg/mL and 208.13µg/mL with comparatively low cytotoxicity against lymphocytes. Moreover, the feasible immunomodulatory effects of Cub-ABPs were determined by evaluating their proliferation and change of CD4+/CD8+ ratio on splenic lymphocytes in vitro. Proliferation and flow cytometry studies revealed that, compared with free ABPs and blank cubosomes, Cub-ABPs proved more effective in promoting lymphocyte proliferation and in triggering the transformation of T-lymphocytes into Th-cells.


Assuntos
Amaranthaceae/química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Composição de Medicamentos , Estabilidade de Medicamentos , Ativação Linfocitária , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura
15.
Int J Nanomedicine ; 12: 6289-6301, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28894367

RESUMO

The success of subunit vaccines has been hampered by the problems of weak or short-term immunity and the lack of availability of nontoxic, potent adjuvants. It would be desirable to develop safe and efficient adjuvants with the aim of improving the cellular immune response against the target antigen. In this study, the targeting and sustained release of simple nanoliposomes containing Lycium barbarum polysaccharides (LBP) as an efficacious immune adjuvant to improve immune responses were explored. LBP liposome (LBPL) with high entrapment efficiency (86%) were obtained using a reverse-phase evaporation method and then used to encapsulate the model antigen, ovalbumin (OVA). We demonstrated that the as-synthesized liposome loaded with OVA and LBP (LBPL-OVA) was stable for 45 days and determined the encapsulation stability of OVA at 4°C and 37°C and the release profile of OVA from LBPL-OVA was investigated in pH 7.4 and pH 5.0. Further in vivo investigation showed that the antigen-specific humoral response was correlated with antigen delivery to the draining lymph nodes. The LBPL-OVA were also associated with high levels of uptake by key dendritic cells in the draining lymph nodes and they efficiently stimulated CD4+ and CD8+ T cell proliferation in vivo, further promoting antibody production. These features together elicited a significant humoral and celluar immune response, which was superior to that produced by free antigen alone.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Imunidade Celular/efeitos dos fármacos , Lipossomos/química , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Medicamentos de Ervas Chinesas/química , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Ovalbumina/química , Ovalbumina/imunologia , Ovalbumina/farmacocinética , Fosfolipídeos/química , Glycine max/química , Vacinas/administração & dosagem , Vacinas/imunologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-28638862

RESUMO

BACKGROUND: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH. MATERIALS AND METHODS: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment. RESULTS: RRRP could reduce mortality with the protection rate about 20.0% compared with that of the viral control (VC) group, finding that RRRP was the most effective against DHAV. The average liver scoring of the VC, blank control (BC), RRRP groups were 3.5, 0, 2.1. Significant difference (P<0.05) appeared between any two groups, demonstrating that it can alleviate liver pathological change. RRRP could make the hepatic injury evaluation indexes similar to BC group while the levels of the VC group were higher than other two groups in general. The levels of SOD, GSH-Px, CAT of RRRP group showed significant higher than that of VC group while the levels of NOS and MDA showed the opposite tendency, thus, RRRP could release peroxidative injury. CONCLUSION: RRRP was the most effective against duck hepatitis A virus (DHAV). RRRP could reduce mortality, alleviate liver pathological change, down-regulate liver lesion score, release peroxidative injury and hepatic injury. The antiviral and peroxidative injury releasing activity of RRRP for DHAV provided a platform to test novel drug strategies for hepatitis A virus in human beings.


Assuntos
Antivirais/administração & dosagem , Vírus da Hepatite do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Doenças das Aves Domésticas/tratamento farmacológico , Rehmannia/química , Animais , Astrágalo/química , Patos , Vírus da Hepatite do Pato/fisiologia , Hepatite Viral Animal/diagnóstico por imagem , Hepatite Viral Animal/metabolismo , Hepatite Viral Animal/virologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/virologia , Raízes de Plantas/química , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/virologia
17.
PLoS One ; 12(4): e0175495, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28394931

RESUMO

The principal target organ of duck hepatitis A virus type 1 (DHAV-1) is duckling liver, which is an energy-intensive organ and plays important roles in body's energy metabolism and conversion. As the "power house" of the hepatocytes, mitochondria provide more than 90% of the energy. However, mitochondria are much vulnerable to the oxidative stress for their rich in polyunsaturated fatty acids. Although previous researches have demonstrated that DHAV-1 could induce the oxidative stress in the serum of the infected ducklings, no related study on the mitochondria during the pathological process of DVH has been reported by far. To address this issue, we examined the HE stained tissue pathological slices, detected the hepatic SOD, CAT and GPX activities and MDA contents and analyzed the ATP content, mitochondrial ultrastructure and the mitochondrial SOD, GPX activities and MDA content in the liver tissues. The results showed that the hepatic redox status was significantly disturbed so that causing the mitochondrial dysfunction, ATP depletion and mitochondrial oxidative stress during the process of the DHAV-1 infection, and a prescription formulated with Hypericum japonicum flavone, Radix Rehmanniae Recens polysaccharide and Salvia plebeia flavone (HRS), which had been demonstrated with good anti-oxidative activity in serum, could effectively alleviate the hepatic injury and the oxidative stress in liver tissue induced by DHAV-1 thus alleviating the mitochondrial injury and oxidative stress. In a word, this research discovers the oxidative stress induced mitochondrial dysfunction and oxidative stress during the DVH pathological process and demonstrates HRS exerts good anti-oxidative activity in liver tissue to protect mitochondria against reactive oxygen species (ROS).


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite do Pato , Hepatite Viral Animal/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Infecções por Picornaviridae/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Patos , Flavonas/farmacologia , Glutationa Peroxidase/metabolismo , Hepatite Viral Animal/metabolismo , Hepatite Viral Animal/mortalidade , Hepatite Viral Animal/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Infecções por Picornaviridae/metabolismo , Infecções por Picornaviridae/mortalidade , Infecções por Picornaviridae/patologia , Polissacarídeos/farmacologia , Distribuição Aleatória , Superóxido Dismutase/metabolismo , Resultado do Tratamento
18.
Int J Biol Macromol ; 98: 506-514, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28167106

RESUMO

The antioxidant action and mechanism of selenizing schisandra chinensis polysaccharide (sSCP) were investigated in chicken embryo hepatocyte (CEH) taking schisandra chinensis polysaccharide (SCP) and N-acetyl-L-cysteine (NAC) as control. The CEH was cultured and treated with sSCP, then exposed to H2O2. The CEHs' viability, apoptosis, ROS and antioxidase contents and the protein expression in MAPKs pathway and mitochondrion-dependence apoptotic signal pathway were assayed. The results showed that sSCP could significantly raise the cell viability and the activities of SOD, CAT and GSH-Px, decrease the cell apoptosis and the content of LDH, AST, ALT and MDA, down-regulate the protein expression of p-JNK1, p-ERK1/2, p-p38, Bax, Caspase 3 and cytochrome C, and up-regulate the protein expression of Bcl-2 in comparison with H2O2 control group. The action of sSCP were stronger than those of SCP and NAC. These results indicated that selenylation modification could significantly enhance the antioxidant activity of SCP, sSCP could significantly protect hepatocyte from oxidative damage induced by H2O2, and its mechanism was by regulating the protein expression in MAPKs and mitochondrion-dependence apoptotic signaling pathways.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Hepatócitos/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Schisandra/química , Selênio/química , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/citologia , Hepatócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
19.
Int J Biol Macromol ; 97: 46-54, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28064055

RESUMO

Chinese angelica polysaccharides (CAP) and selenizing CAP (sCAP) were prepared and identified through FTIR and SEM observation. Their antioxidant activities in vitro and hepatoprotective effects in vivo were compared by free radical-scavenging tests or with CCl4-induced hepatic injury model mice. The results showed that for DPPH radical, superoxide anion and hydroxyl radical, the scavenging capabilities of sCAP were significantly stronger than those of CAP. In hepatic injury model mice, sCAP could significantly reduce ALT, AST and ALP contents and raised TP content in serum, significantly reduce MDA and ROS contents and raised SOD and T-AOC activities in liver homogenate in comparison with CAP; obviously relieve the pathological changes of liver and significantly inhibit the expressions of p-ERK, p-JNK and p-p38 protein as compared with those in model control group. These results indicate that selenylation modification can enhance the antioxidant and hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway.


Assuntos
Angelica sinensis/química , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Selênio/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção/efeitos dos fármacos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
20.
Molecules ; 21(12)2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27983593

RESUMO

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.


Assuntos
Medicina Tradicional Chinesa , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Animais , Humanos , Polissacarídeos/química
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