Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
FASEB J ; 35(9): e21777, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34403519

RESUMO

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Kumis/efeitos adversos , Mycobacterium bovis/efeitos dos fármacos , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/análise , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Cavalos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Tuberculose Pulmonar/dietoterapia , Tuberculose Pulmonar/metabolismo
2.
BMC Cancer ; 21(1): 644, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34053447

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. METHODS: We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). RESULTS: A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in 'cell cycle' and 'oocyte meiosis' related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. CONCLUSIONS: The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients' prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Neoplasias de Mama Triplo Negativas/genética , Mama/patologia , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Mapas de Interação de Proteínas/genética , Curva ROC , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
3.
Biomed Pharmacother ; 137: 111341, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561646

RESUMO

Mycobacterium bovis (M. bovis) is a member of mycobacterium tuberculosis complex (MTBC), and a causative agent of chronic respiratory disease in a wide range of hosts. Bacillus Calmette-Guerin (BCG) vaccine is mostly used for the prevention of childhood tuberculosis. Further substantial implications are required for the development and evaluation of new tuberculosis (TB) vaccines as well as improving the role of BCG in TB control strategies. In this study, we prepared PLGA nanoparticles encapsulated with argF antigen (argF-NPs). We hypothesized, that argF nanoparticles mediate immune responses of BCG vaccine in mice models of M. bovis infection. We observed that mice vaccinated with argF-NPs exhibited a significant increase in secretory IFN-γ, CD4+ T cells response and mucosal secretory IgA against M. bovis infection. In addition, a marked increase was observed in the level of secretory IL-1ß, TNF-α and IL-10 both in vitro and in vivo upon argF-NPs vaccination. Furthermore, argF-NPs vaccination resulted in a significant reduction in the inflammatory lesions in the lung's tissues, minimized the losses in total body weight and reduced M. bovis burden in infected mice. Our results indicate that BCG prime-boost strategy might be a promising measure for the prevention against M. bovis infection by induction of CD4+ T cells responses and mucosal antibodies.


Assuntos
Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Mycobacterium bovis , Nanopartículas/administração & dosagem , Ornitina Carbamoiltransferase/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Tuberculose Bovina/prevenção & controle , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Bovinos , Linhagem Celular , Modelos Animais de Doenças , Feminino , Imunoglobulina A Secretora/metabolismo , Imunoglobulina G/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-1beta/sangue , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium bovis/patogenicidade , Nanopartículas/química , Ornitina Carbamoiltransferase/administração & dosagem , Ornitina Carbamoiltransferase/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Baço/microbiologia , Baço/patologia , Fator de Necrose Tumoral alfa/sangue
4.
Mol Cancer ; 20(1): 7, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397409

RESUMO

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.


Assuntos
Mimetismo Molecular , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Neovascularização Patológica/patologia , Hipóxia Tumoral , Microambiente Tumoral , Animais , Humanos , Células-Tronco Neoplásicas/patologia
5.
Mol Oral Microbiol ; 36(1): 67-79, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33316854

RESUMO

Ligustrum robustum (Roxb.) Blume is utilized as a traditional Chinese herbal tea with various health benefits and protective effects. Streptococcus mutans is an important cariogenic oral bacteria species. The present study aimed to assess the influence of Ligustrum robustum extract (LRE) on the biofilm formation of S. mutans and the mechanism of its action, as well as to identify its chemical components. For chemical identification, HPLC-MS and nuclear magnetic resonance were applied and four identified phytochemicals were reported (Ligurobustoside B, Ligurobustoside N, Ligurobustoside J, and Ligurobustoside C). The dose-dependent (0.5 to 2.0 µg/µL) antimicrobial toxicity of LRE against S. mutans biofilm formation and exopolysaccharide (EPS) synthesis was evaluated by confocal laser scanning microscopy (CLSM), Crystal violet stain, and CFU counting. The microstructure of S. mutans biofilm treated with LRE was investigated both on glass coverslips and ex vivo bovine dental enamel by scanning electron microscopy (SEM). Moreover, LRE downregulated the expression of S. mutans glucosyltransferase-encoding genes gtfB, gtfC, and gtfD, and the quorum sensing (QS) factors comD and comE, suggesting its toxic mechanism. In addition, the result of CCK-8 test on human oral cells revealed an acceptable biocompatibility of LRE. These findings indicated the possible application of this daily consumed herbal tea for caries prevention.


Assuntos
Cárie Dentária , Ligustrum , Animais , Biofilmes , Bovinos , Cárie Dentária/prevenção & controle , Humanos , Extratos Vegetais/farmacologia , Streptococcus mutans
6.
Pharmaceutics ; 12(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271900

RESUMO

Mycobacterium bovis (M. bovis) is a member of the Mycobacterium tuberculosis complex imposing a high zoonotic threat to human health. The limited efficacy of BCG (Bacillus Calmette-Guérin) and upsurges of drug-resistant tuberculosis require new effective vaccination approaches and anti-TB drugs. Poly (lactic-co-glycolic acid) (PLGA) is a preferential drug delivery system candidate. In this study, we formulated PLGA nanoparticles (NPs) encapsulating the recombinant protein bovine neutrophil ß-defensin-5 (B5), and investigated its role in immunomodulation and antimicrobial activity against M. bovis challenge. Using the classical water-oil-water solvent-evaporation method, B5-NPs were prepared, with encapsulation efficiency of 85.5% ± 2.5%. These spherical NPs were 206.6 ± 26.6 nm in diameter, with a negatively charged surface (ζ-potential -27.1 ± 1.5 mV). The encapsulated B5 protein from B5-NPs was released slowly under physiological conditions. B5 or B5-NPs efficiently enhanced the secretion of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-10 in J774A.1 macrophages. B5-NPs-immunized mice showed significant increases in the production of TNF-α and immunoglobulin A (IgA) in serum, and the proportion of CD4+ T cells in spleen compared with B5 alone. In immunoprotection studies, B5-NPs-immunized mice displayed significant reductions in pulmonary inflammatory area, bacterial burden in the lungs and spleen at 4-week after M. bovis challenge. In treatment studies, B5, but not B5-NPs, assisted rifampicin (RIF) with inhibition of bacterial replication in the lungs and spleen. Moreover, B5 alone also significantly reduced the bacterial load in the lungs and spleen. Altogether, our findings highlight the significance of the B5-PLGA NPs in terms of promoting the immune effect of BCG and the B5 in enhancing the therapeutic effect of RIF against M. bovis.

7.
Arch Oral Biol ; 116: 104762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474211

RESUMO

OBJECTIVE: The present study aimed to evaluate the effect of Rhodiola rosea extract (RE) on Streptococcus mutans biofilm formation and the relevant mechanism of its action. METHODS: The effect of RE on the biofilm formation and extracellular polysaccharides (EPS) synthesis of S. mutans was assessed by confocal laser scanning microscopy (CLSM), crystal violet staining and CFU counting method. Scanning electron microscopy (SEM) was applied to observe the surface morphology of S. mutans biofilms formed on glass coverslips and dental enamel. To study the relevant mechanism, quantitative real time PCR (qRT-PCR) and zymogram assay were applied to measure the expression of virulence genes and the enzymatic activity of glucosyltransferases (Gtfs) under the treatment of RE. The CCK-8 assay was also performed on macrophages (RAWs) and human oral keratinocytes (HOKs) in order to evaluate its biocompatibility. RESULTS: As a result, RE inhibited the biofilm formation and EPS synthesis of S. mutans. RE also suppressed the expression of gtf genes and quorum sensing (QS) system as well as the enzymatic activity of Gtf proteins. Moreover, RE exhibited a good biocompatibility to human cells. CONCLUSIONS: This study provides the evidence for RE as a novel anti-biofilm agent for clinical use.


Assuntos
Biofilmes , Cárie Dentária , Rhodiola , Biofilmes/efeitos dos fármacos , Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Humanos , Extratos Vegetais/farmacologia , Streptococcus mutans/genética , Virulência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...