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1.
J Mater Chem B ; 8(3): 515-522, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31840711

RESUMO

The development of magnetic iron oxide nanoparticles with novel topological magnetic domain structures, such as the vortex-domain structure, is a promising strategy for improving the application performance of conventional superparamagnetic iron oxides while maintaining their good biocompatibility. Here, we fabricated a new kind of magnetic-vortex nanoparticles, i.e., ellipsoidal magnetite nanoparticles (EMPs), for cancer magnetic hyperthermia. The magnetization configurations and switching behaviours of the EMPs were analyzed by analytical simulations and Lorentz TEM, demonstrating the magnetic vortex structures of both single and coupled EMPs. The EMP treatment of 4T1 cells exposed to an alternating magnetic field (AMF) induced a significant decrease in the cell viability by ∼51.5%, which indicated a much higher cytotoxic effect in comparison with commercial superparamagnetic iron oxides (Resovist, ∼12.0%). In addition, the in vivo high efficacy of 4T1 breast tumor inhibition was also achieved by using EMP-mediated magnetic hyperthermia. Our results not only provide a new type of magnetic-vortex nanoparticles for efficient hyperthermia but also enrich the family of magnetic iron oxide nanoparticles for various biomedical applications.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31736338

RESUMO

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of HBV-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort (n=40). The selected proteins were confirmed using ELISA in a validation cohort (n=140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary alpha-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients as validated by western blot and ELISA. U-AFP had a strong correlation with serum AFP-L3 (Pearson r =0.944, p < 0.0001), indicating that u-AFP may be derived from circulating blood. The AUC of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC and studies on large samples are needed to validate the result.

3.
Nano Lett ; 19(6): 4118-4125, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31140281

RESUMO

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded Fe3O4 nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

4.
Int Immunopharmacol ; 73: 172-180, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100712

RESUMO

BACKGROUND: Although γδ T cells have been reported to be closely related to the immunopathogenesis of some viral infectious diseases, the changes or roles of γδ T cells in the development of hand, foot, and mouth disease (HFMD) remain unclear. METHODS: Peripheral γδ T cells and their subsets were determined by surface (γδ TCR, Vδ1 TCR, Vδ2 TCR, CD45RA, and CD27) or intracellular (IFN-γ, TNF-α, CD107a, and Granzyme B) markers in healthy controls (HCs) and HFMD patients with FACS. The plasma levels of IFN-γ, TNF-α, IL-6, and MCP-1 were measured by ELISA. Differences in γδ T cells or their subsets and correlations between γδ T cells and inflammation indicators were statistically analyzed. RESULTS: Compared to HCs, HFMD patients showed increased effector γδ T and TNF-α+γδ T cells and plasma TNF-α levels, especially in severe cases. In addition, significantly increased Vδ1 T and IFN-γ+γδ T cells and other plasma inflammatory cytokines were further found in severe patients. Furthermore, EV71+ severe patients showed significantly increased effector and cytokine-producing γδ T cells, while the EV71- severe patients displayed significantly greater plasma cytokine levels. The percentage of IFN-γ+γδ T or TNF-α+γδ T cells was positively correlated with that of effector γδ T cells. There was a positive correlation between the proportion of Vδ1 T cells and white blood cell (WBC) count or the proportion of IFN-γ+γδ T or TNF-α+γδ T cells and neutrophil (N) count, while there was a negative correlation between Vδ2 T cells and WBC or N count. Moreover, the percentages of Vδ1 T and effector γδ T cells in the acute phase of disease declined significantly to normal levels during the recovery phase. CONCLUSIONS: Increased effector γδ T cells with enhanced cytokine production were remarkably observed in severe HFMD patients, which was also associated with clinical inflammation parameters. These data indicated that γδ T cells might be involved in inflammatory abnormalities in severe HFMD.


Assuntos
Citocinas/imunologia , Doença de Mão, Pé e Boca/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Pré-Escolar , Feminino , Doença de Mão, Pé e Boca/virologia , Herpesvirus Humano 4/genética , Humanos , Lactente , Masculino , RNA Viral
5.
Int J Infect Dis ; 83: 56-63, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959250

RESUMO

OBJECTIVES: With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after liver transplantation (LT). Whether ribavirin (RBV) is needed by patients after LT in combination with SOF-based DAAs remains to be determined. This meta-analysis was conducted to evaluate the necessity of RBV with SOF-based DAAs for post-LT patients. METHODS: PubMed, Web of Science, Cochrane Library and EMBASE databases were systematically searched for eligible studies from the databases' inceptions until November 2018. We accepted the studies that included HCV recurrence in post-LT patients who were treated with SOF-based DAAs ± RBV, and evaluated the rate of sustained virological response 12 weeks (SVR12) after the end of treatment. RESULTS: Twelve studies, comprising a total of 1466 LT recipients, were included in this study. The pooled SVR12 of these patients was 91% (95% CI: 84% to 95%). There was no statistical difference of SVR12 in the patients treated with SOF-based DAAs + RBV versus -RBV group (risk ratio [RR] = 0.97; 95% CI: 0.92 to 1.03; P = 0.35) by different therapy duration (P = 0.26), with different targets of DAAs (P = 0.13) and in different regions (P = 0.34) but a tendency for a higher incidence of anemia in the +RBV group than in the -RBV group (RR = 5.18; 95% CI: 3.41 to 7.86; p < 0.00001). CONCLUSION: The addition of RBV may not contribute to a higher SVR rate and could increase the incidence of anemia, so RBV is not necessary in SOF-based DAAs for patients with HCV recurrence after LT.


Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Transplante de Fígado , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Quimioterapia Combinada , Feminino , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resposta Viral Sustentada
6.
PeerJ ; 7: e6645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923657

RESUMO

Background: Liver fibrosis is often a consequence of chronic liver injury, and has the potential to progress to cirrhosis and liver cancer. Despite being an important human disease, there are currently no approved anti-fibrotic drugs. In this study, we aim to identify the key genes and pathways governing the pathophysiological processes of liver fibrosis, and to screen therapeutic anti-fibrotic agents. Methods: Expression profiles were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified by R packages (Affy and limma). Gene functional enrichments of each dataset were performed on the DAVID database. Protein-protein interaction (PPI) network was constructed by STRING database and visualized in Cytoscape software. The hub genes were explored by the CytoHubba plugin app and validated in another GEO dataset and in a liver fibrosis cell model by quantitative real-time PCR assay. The Connectivity Map L1000 platform was used to identify potential anti-fibrotic agents. Results: We integrated three fibrosis datasets of different disease etiologies, incorporating a total of 70 severe (F3-F4) and 116 mild (F0-F1) fibrotic tissue samples. Gene functional enrichment analyses revealed that cell cycle was a pathway uniquely enriched in a dataset from those patients infected by hepatitis B virus (HBV), while the immune-inflammatory response was enriched in both the HBV and hepatitis C virus (HCV) datasets, but not in the nonalcoholic fatty liver disease (NAFLD) dataset. There was overlap between these three datasets; 185 total shared DEGs that were enriched for pathways associated with extracellular matrix constitution, platelet-derived growth-factor binding, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling. In the PPI network, 25 hub genes were extracted and deemed to be essential genes for fibrogenesis, and the expression trends were consistent with GSE14323 (an additional dataset) and liver fibrosis cell model, confirming the relevance of our findings. Among the 10 best matching anti-fibrotic agents, Zosuquidar and its corresponding gene target ABCB1 might be a novel anti-fibrotic agent or therapeutic target, but further work will be needed to verify its utility. Conclusions: Through this bioinformatics analysis, we identified that cell cycle is a pathway uniquely enriched in HBV related dataset and immune-inflammatory response is clearly enriched in the virus-related datasets. Zosuquidar and ABCB1 might be a novel anti-fibrotic agent or target.

7.
iScience ; 7: 170-179, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30245369

RESUMO

Developing a sensitive, low-cost, and easy-to-use point-of-care testing system for genotyping is important for informing treatment decisions and predicting the risk of underlying diseases. Conventional methods normally require complex operational procedures as well as expensive and sophisticated instruments. Here, we report a general approach that enables us to detect the genotype of multiple sample types directly without DNA purification. Moreover, the PCR results can be further quantitatively analyzed based on a magnetic lateral flow assay (MLFA) system, which avoids multiple steps needed for conventional nucleic acid biosensors. As a demonstration, we show that three genotypes of aldehyde dehydrogenase 2 (ALDH2) can be identified using a small volume of sample with an accuracy of 100% and a sensitivity of 1.0 × 102 cells/µL, which are better than those of the gold standard methods. We believe that the direct PCR-MLFA system represents a significant advance toward the development of portable, sensitive biomedical platforms.

8.
Int Immunopharmacol ; 62: 59-66, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29990695

RESUMO

BACKGROUND AND AIMS: Much evidence indicates that the soluble antigens secreted by hepatitis B virus (HBV) inhibit the function of the immune system. The aim of this study is to investigate, after treatment with nucleoside (acid) analogs (NAs) and the inhibition of viral replication, whether the immune systems of patients with a peripheral blood HBV-DNA level <1000 IU/mL, hepatitis B e antigen (HBeAg) disappearance, and a decrease in hepatitis B surface antigen (HBsAg) levels could be reconstructed. METHODS: The frequency and phenotype of circulating natural killer (NK) cells, dendritic cells (DCs), T-helper (Th) cells, regulatory T (Treg) cells, CD4+, CD8+ T cells, T follicular helper (Tfh) cells and B cells subtypes were tested by flow cytometry in chronic hepatitis B (CHB) patients and healthy controls (HCs). The levels of HBV-related serum HBsAg, HBeAg, HBV-DNA load, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. RESULTS: Regarding the innate immune system, an increased frequency of CD56dim NK cells was found in the therapeutic response (TR) group compared with that in the immune-active phase (IA) group. Additionally, regarding the adaptive immune system, the Th17/CD4+CD25+CD127dimTreg ratio was reduced in the TR group. Additionally, the frequency of CD40L+CXCR5+CD4+T cells and CD40+CD19+CD27+CD38+B cells was significantly higher than that of HCs, while that of PDL1+CD19+ B cells was lower. Furthermore, the frequencies of CTLA4+CD4+T cells and CTLA4+CD8+T cells in patients with CHB were significantly higher than those in HCs. CONCLUSION: After NA treatment and the inhibition of viral replication, circulating CD56dim NK cells and the balance of Th17/Treg can be recovered. Restoring circulating CD56dim NK cells and the Th17/Treg balance may help reduce HBsAg levels in patients.


Assuntos
Antivirais/uso terapêutico , Antígeno CD56/sangue , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Células Matadoras Naturais/imunologia , Linfócitos T Reguladores/citologia , Células Th17/citologia , Adulto , Estudos de Casos e Controles , DNA Viral/sangue , Feminino , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Resultado do Tratamento , Carga Viral , Adulto Jovem
9.
J Biomed Nanotechnol ; 14(6): 1135-1146, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29843878

RESUMO

Doxorubicin (Dox) is one of the most widely used chemotherapeutic agents for many types of cancer, including hepatocellular carcinoma. However, clinical applications of Dox are limited due to its non-selective cytotoxicity that results in severe adverse effects. To tackle this problem targeted delivery of Dox exclusively to tumour milieu has become clinically prioritised. In this study, we first synthesized and validated Dextran coated GoldMag Nanoparticles (DGMNs) as a potential delivery vehicle for Dox. We then evaluated the cytotoxicity of Dox-DGMNs, the drug and carrier composites, under guidance of external magnetic field (EMF) in hepatocellular carcinoma cell lines and in tumour grafts. Intriguingly, DGMNs exhibited the capacity to prolong Dox release in vitro; hence, Dox-DGMNs significantly enhanced the therapeutic efficiency of the drug in vitro and in vivo, especially under EMF. However, DGMNs were able to significantly decrease systemic adverse effects and inhibit tumour growth compared to the intravenous application of free Dox. Molecular analysis revealed that tumour cells were more affected by Dox-DGMNs with EMF than Dox-DGMNs or Dox alone in terms of apoptosis and DNA damage marker expression. Overall, DGMNs exhibited a substantial potential to serve as a promising drug delivery carrier for magnetically targeted cancer therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Linhagem Celular Tumoral , Dextranos , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas Metálicas
10.
J Clin Transl Hepatol ; 6(1): 11-17, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29577027

RESUMO

Background and Aims: Few previous studies have reported on a combination response (hepatitis B virus (HBV) DNA undetected, alanine aminotransferase normalization and hepatitis B e antigen (HBeAg) seroconversion) following nucleos(t)ide analogue (NAs) long-term therapy in patients with chronic hepatitis B (CHB). This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response, particularly in optimal patients (baseline alanine aminotransferase level ≥5 upper limit of normal and HBV DNA level <109 copies/mL). Methods: In total, 280 HBeAg-positive CHB patients were enrolled in this study. Among them, 190 were treated with entecavir and 90 were treated with telbivudine. Results: The cumulative rates of combination response in the total number of patients were 8.6% at 1 year, 13.2% at 2 years, 19.1% at 3 years, 24.2% at 4 years and 26.0% at 5 years. In optimal patients, the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years (p = 0.043); the trend of the cumulative rate was not strong at the later time. Interestingly, in optimal patients, combination response mainly occurred in the first 3 years. Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients (hazard ratio: 16.321; p = 0.000). During the 3 years, the proportion with aspartate aminotransaminase to platelet ratio index ≤0.5 increased from 15.6% at baseline to 71.3% at year 3. Conclusions: Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients; a new switch treatment strategy modification should be considered, particularly in optimal patients.

11.
Inflammation ; 41(2): 579-594, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29234949

RESUMO

We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) significantly inhibited cyclooxygenase 2 (COX-2) expression and improved the progression of liver fibrosis. The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin, aspirin, NS-398, and vitamin C. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, curcumin, aspirin, NS-398, or vitamin C at the indicated concentration for 2 h; then, the cells were stimulated with 1 µg/mL lipopolysaccharide (LPS) for 24 h. The levels of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, PGE2, NO, and GSH, and the activities of COX-2, SOD, and CAT, and the transcription factors involved in inflammation, such as NF-κB, c-Jun, and Nrf2, were measured. Curc-mPEG454 showed lower cytotoxicity (IC50 57.8 µM) when compared with that of curcumin (IC50 32.6 µM) and inhibited the release of the inflammatory cytokines IL-6, TNF-α, IL-1ß, and MCP-1 in a concentration-dependent manner. At 16 µM, Curc-mPEG454 was most potent in the suppression of COX-2 expression at a transcriptional level rather than in the suppression of the catalytic activity of COX-2. Like curcumin, Curc-mPEG454 significantly reduced intracellular ROS production and enhanced the activities of SOD and CAT and the level of GSH to protect cells from LPS-induced oxidative injury. Further, its anti-inflammatory and antioxidation mechanisms are related to inhibition of NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activation of Nrf2. Taken together, these findings indicate that PEGylation of curcumin not only improves its biological properties but also interferes with multiple targets involved in the inflammatory response. Curc-mPEG454 is a powerful and beneficial anti-inflammatory and antioxidant agent that merits further investigation. Graphical Abstract ᅟ.


Assuntos
Curcumina/análogos & derivados , Curcumina/farmacologia , Polietilenoglicóis/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Células RAW 264.7 , Fator de Transcrição RelA/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
12.
Biomed Res Int ; 2017: 8234507, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28770225

RESUMO

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.


Assuntos
Antígenos CD36/metabolismo , Curcumina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fígado Gorduroso/tratamento farmacológico , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo
13.
PLoS One ; 12(7): e0180725, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28708844

RESUMO

PURPOSE: To estimate the diagnostic accuracy of Xpert MTB/RIF, a systematic review and meta-analysis were carried out. METHODS: Up to June 20, 2015, multiple databases were screened for relevant studies. RESULTS: Accordingly, 106 studies included 52,410 samples were selected. Diagnostic accuracy of Xpert MTB/RIF for TB detection was validated against either culture or a composite reference standard (CRS). Additionally, selected studies were further subgrouped in four groups based on sample's type, subject's age, status of HIV co-infection and smear-positivity. The overall pooled sensitivity and specificity of Xpert MTB/RIF was 0.85 (95% confidence interval [CI] 0.82-0.88) and 0.98 (95% CI 0.96-0.98), respectively, compared to culture; while it was 0.59 (95% CI 0.44-0.72) and 0.99 (95% CI 0.97-1.00) compared to CRS. The overall sensitivity was lower in countries with high TB prevalence than countries with middle/low prevalence (0.84, 95% CI: 0.80-0.88 versus 0.89, 95% CI: 0.84-0.93). Furthermore, Xpert MTB/RIF has higher sensitivity in patients with positive smears (0.99, 95% CI 0.97-0.99), in patients with pulmonary TB samples (0.87, 95% CI 0.83-0.90), in adults (0.82, 95% CI 0.76-0.86) and in HIV-positive patients (0.81, 95% CI 0.73-0.87). CONCLUSIONS: Taken together, Xpert MTB/RIF is a quick and accurate diagnostic assay for TB which will significantly help the physicians to make their clinical decisions.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose/diagnóstico , Área Sob a Curva , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Bases de Dados Factuais , Infecções por HIV/complicações , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Curva ROC , Padrões de Referência , Tuberculose/complicações , Tuberculose/microbiologia
14.
Sci Rep ; 7(1): 3383, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28611459

RESUMO

A new acidly sensitive PEGylated polyethylenimine linked by Schiff base (PEG-s-PEI) was designed to render pH-sensitive PEGylation nanoassemblies through multiple interactions with indomethacin and docetaxel (DTX). DTX nanoassemblies driven by PEG-s-PEI thus formulated exhibited an excellent pH-sensitivity PEGylation cleavage performance at extracellular pH of tumor microenvironment, compared to normal tissues, thereby long circulated in blood but were highly phagocytosed by tumor cells. Consequently, this smart pH-sensitive PEGylation cleavage provided an efficient strategy to target tumor microenvironment, in turn afforded superior therapeutic outcome in anti-tumor activity.


Assuntos
Proliferação de Células/efeitos dos fármacos , Docetaxel/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias Experimentais/tratamento farmacológico , Polietilenoglicóis/química , Polietilenoimina/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Docetaxel/química , Docetaxel/farmacocinética , Portadores de Fármacos/química , Humanos , Concentração de Íons de Hidrogênio , Indometacina/administração & dosagem , Indometacina/química , Indometacina/farmacocinética , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Neoplasias Experimentais/patologia , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Células Tumorais Cultivadas
15.
Int Immunopharmacol ; 46: 48-55, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28259000

RESUMO

BACKGROUND: Th17/Treg imbalance and the levels of related cytokines are essential in the pathogenesis of autoimmune and infectious diseases. The aim of the current study was to assess the Treg/Th17 balance and the levels of related cytokines associated with various degrees of liver injury in patients with chronic hepatitis B virus (HBV) infection. METHODS: The proportions of peripheral Th17, Treg and Th1 cells in 7 patients classified as asymptomatic hepatitis B virus carriers (AsCs), 38 patients with low or moderate grade chronic hepatitis B (CHB-LM), 20 patients with chronic severe hepatitis B (CSHB), and 10 healthy controls (HCs) were determined by flow cytometry. The levels of related cytokines and the mRNA expression levels of transcription factors were measured using Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-PCR), respectively. RESULTS: The Th17 cell frequency and the mRNA expression levels of RORc were increased in the CSHB group. The Treg cell frequency was increased and Th1 cell frequency and the mRNA expression levels of T-bet were decreased in chronic HBV infection. The levels of IL-21 were increased in the CSHB group and were positively correlated with AST, TB and DB in patients with chronic HBV infection. The Th17/Treg ratio was increased in the CSHB group and was positively correlated with liver injury in chronic HBV infection. CONCLUSIONS: Th17/Treg imbalance and increased IL-21 are associated with liver injury in patients with chronic HBV infection. Restoring the Th17/Treg balance may be a novel immunotherapy for patients with CSHB.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Interleucinas/metabolismo , Fígado/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adolescente , Adulto , Idoso , Doenças Assintomáticas , Células Cultivadas , Feminino , Hepatite B Crônica/virologia , Humanos , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
J Nanosci Nanotechnol ; 16(6): 6258-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27427699

RESUMO

Curcumin, a polyphenol extracted from turmeric (Curcuma longa), has emerged as a potent multimodal cancer-preventing agent. It may attenuate the spread of cancer and render chemotherapy more effective. However, curcumin is neither well absorbed nor well retained in the blood, resulting in low efficacy. In an attempt to enhance the potency and to improve the bioavailability of curcumin, new delivery agents, hydroxypropyl-beta-cyclodextrin (HP-ß-CD)-modified GoldMag nanoparticles (CD-GMNs) were designed and synthesized to incorporate curcumin. The CD-GMNs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA), X-ray Diffraction (XRD), Dynamic Light Scattering measurements (DLS), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM) analyses. For the magnetic carrier of CD-GMNs, the content of HP-ß-CD was 26.9 wt%. CD-GMNs have a saturation magnetization of 22.7 emu/g with an average hydrodynamic diameter of 80 nm. The curcumin loading, encapsulation efficiency and releasing properties in vitro were also investigated. The results showed that the drug encapsulation ratio was 88% and the maximum curcumin loading capacity of CD-GMNs was 660 µg/5 mg. In vitro drug release studies showed a controlled and pH-sensitive curcumin release over a period of one week. Collectively, our data suggest that HP-ß-CD-modified GoldMag nanoparticles can be considered to form a promising delivery system for curcumin to tumor sites. Targeting can be achieved by the combined effects of the application of an external magnetic field and the effect on drug release of lower pH values often found in the tumor microenvironment.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Ouro/química , Nanopartículas de Magnetita/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/síntese química , 2-Hidroxipropil-beta-Ciclodextrina , Técnicas de Química Sintética , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas
17.
Sci Rep ; 6: 26296, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27192960

RESUMO

Vδ2 γδ (Vδ2) T cells, a major human γδ T cell subset, exhibit broad anti-tumor and anti-infective activity; however, their precise role in chronic hepatitis C virus (HCV) infections remains unclear. In this study, we analyzed the phenotype and function of Vδ2 T cells in 43 HCV-infected patients compared to 39 healthy controls (HCs). Vδ2 T cells from HCV-infected patients were activated and differentiated into effector cells. Vδ2 T cells in patients expressed significantly higher levels of natural killer (NK) cell markers CD56 and CD16 than in HCs, acquiring cytotoxic NK-like phenotype. The Vδ2 T cell phenotype was associated with increased cytolytic effector molecules expression in HCV-infected patients with elevated serum ALT levels. Surprisingly, Vδ2 T cells in patients had a markedly impaired capacity to produce IFN-γ. Further in vitro and in vivo analysis showed that interferon-α, which was induced during HCV infection, caused Vδ2 T cell function bias toward cytotoxicity. These results suggest a functional dichotomy for Vδ2 T cells in chronic HCV infections: a role in cytotoxicity but not for IFN-γ production, which may contribute to both the liver inflammation and HCV persistence.


Assuntos
Hepatite C Crônica/imunologia , Interferon gama/biossíntese , Linfócitos Intraepiteliais/imunologia , Adolescente , Adulto , Alanina Transaminase/sangue , Estudos de Casos e Controles , Citotoxicidade Imunológica , Feminino , Humanos , Interferon-alfa/metabolismo , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade
18.
Mol Immunol ; 73: 37-45, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27037894

RESUMO

UNLABELLED: Hepatitis B e antigen (HBeAg) seroconversion constitutes a significant milestone in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB), but studies have yet to identify the specific humoral immune mechanisms behind the process or any accurate markers that can determine the virus-host immune status and, thereby, predict the degree of HBeAg seroconversion achievable. In the present longitudinal study, higher frequencies of circulating CXCR5(+)CD4(+) T cells and CD19(+)CD38(+) B cells were found in peginterferon-α treated HBeAg-positive CHB patients in whom HBeAg seroconversion had been achieved. What's more, both cell types peaked at 24 weeks for the HBeAg seroconversion group, while showing only a slight variation in the HBeAg non-seroconversion group. In addition, circulating CXCR5(+)CD4(+) T cells and hepatitis B surface antigens (HBsAg) were assessed at 24 weeks and 12 weeks, respectively, and the use of their ratio was explored in terms of its ability to predict HBeAg seroconversion. CONCLUSION: Dysfunction of the humoral immune response mediated by CXCR5(+)CD4(+) T cells is associated with the failure of HBeAg seroconversion. The CXCR5(+)CD4(+) T cells/HBsAg ratio is an ideal marker for predicting HBeAg seroconversion in CHB patients.


Assuntos
Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Interferon-alfa/uso terapêutico , Adulto , Feminino , Citometria de Fluxo , Humanos , Imunidade Humoral/imunologia , Estudos Longitudinais , Masculino , Soroconversão/efeitos dos fármacos , Soroconversão/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto Jovem
19.
Int Immunopharmacol ; 34: 235-243, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26971227

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with abnormal T cell and B cell immune responses. T follicular helper (TFH) cells are a subset of CD4(+) T-helper cells and can activate B cells. This study aimed to investigate the role of circulating CXCR5(+)CD4(+) TFH cells, CD19(+) B cells and the associated cytokines in patients with chronic HCV infection. METHODS: The frequencies and phenotypes of circulating TFH cells and B cell subtypes were characterized using flow cytometry in chronic hepatitis C (CHC) patients and in healthy controls (HCs). The expression of IFN-γ, IL-12p70, IL-5, IL-13, IL-17F, IL-22, IL-23, TGF-ß1, IL-10 and IL-21 associated with Th1, Th2, Th17, regulatory T cells (Treg) and TFH cells were analyzed using a Quantibody array. The patients' clinical parameters were detected, and the effect of pegylated interferon plus ribavirin treatment on these immune indicators in CHC patients was determined. RESULTS: The frequency of CXCR5(+)CD4(+) T cells was significantly higher in CHC patients compared to HCs. There were no significant differences in CD19(+) B cells, CD19(+)CD27(+) B cells, or CD19(+)CD38(+) B cells between CHC patients and HCs. The expressions of cytokines associated with the CD4(+) Th lineage were higher in CHC patients than in HCs, except for IL-21. Patients with rapid virological response (RVR) showed an increased CXCR5(+)CD4(+) T cell count and decreased PD-1(+) CXCR5(+)CD4(+) T cell count compared to non-RVR patients after PEG-IFN/ribavirin treatment. CONCLUSIONS: These data demonstrate that circulating TFH cells and CD4(+) Th lineage-associated cytokines may play a role in HCV-related immune responses.


Assuntos
Linfócitos B/imunologia , Hepatite C Crônica/terapia , Hepatite C/imunologia , Imunoterapia/métodos , Fígado/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Antígenos CD19/metabolismo , Citocinas/metabolismo , Feminino , Fibrose , Hepatite C Crônica/imunologia , Humanos , Interferon-alfa/uso terapêutico , Fígado/efeitos dos fármacos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Receptores CXCR5/metabolismo , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
20.
Nanoscale ; 7(25): 11155-62, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26062012

RESUMO

Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 µg mL(-1)) compared to free Dox (IC50 = 0.533 µg mL(-1)). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.


Assuntos
Antineoplásicos/química , Dextranos/química , Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas de Magnetita/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentais/patologia , Coelhos , Ensaios Antitumorais Modelo de Xenoenxerto
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