Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
1.
Malar J ; 20(1): 374, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538247

RESUMO

BACKGROUND: Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. METHODS: The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. RESULTS: Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and - 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. CONCLUSIONS: This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.


Assuntos
Antígenos de Protozoários/genética , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Seleção Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Guiné Equatorial , Humanos , Lactente , Malária Falciparum/parasitologia , Pessoa de Meia-Idade , Adulto Jovem
2.
J Clin Lab Anal ; 34(6): e23216, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31967356

RESUMO

BACKGROUND: Clinically, D-dimer (DD) levels are mainly used to exclude diseases such as deep venous thrombosis (DVT). In clinical testing, DD assays can be subjected to interference that may cause false results, which directly affect the clinical diagnosis. Our hypothesis was that the 95% confidence intervals (CIs) of the fibrin degradation product (FDP)/DD and fibrinogen (Fib)/DD ratios were used to identify these false results and corrected via multiple dilutions. METHODS: In total, 16 776 samples were divided into three groups according to the DD levels detected by Sysmex CS5100 and CA7000: Group A, DD ≥ 2.0 µg/mL fibrinogen equivalent unit (FEU); group B, 0.5 < DD < 2.0 µg/mL FEU; and group C, DD ≤ 0.5 µg/mL FEU. The 95% CIs of the FDP/DD and Fib/DD ratios were calculated. Six abnormal DD results were found according to the 95% CIs. For verification, we performed multiple dilutions, compared the results with those of other instruments, and tested the addition of heterophilic blocking reagent (HBR). RESULTS: The median and 95% CI of the FDP/DD ratio were 3.76 and 2.25-8.15 in group A, 5.63 and 2.86-10.58 in group B, 10.23 and 0.91-47.71 in groups C, respectively. For the Fib/DD ratio, the 95% CIs was 0.02-2.21 in group A, 0.68-8.15 in group B, and 3.82-55.27 in groups C. Six abnormal results were identified after multiple dilutions, by comparison with other detection systems, and after HBR addition. CONCLUSIONS: The FDP/DD ratio is more reliable for identifying false results. If the FDP/DD ratio falls outside the 95% CI, it should be verified by different methods.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Imunoturbidimetria/métodos , Adulto , Artefatos , Intervalos de Confiança , Reações Falso-Positivas , Feminino , Humanos , Imunoturbidimetria/normas , Masculino , Pessoa de Meia-Idade , Gravidez , Trombose Venosa/sangue
3.
J Clin Lab Anal ; 33(2): e22687, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30320416

RESUMO

BACKGROUND: Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article. METHODS: Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature. RESULTS: The D-dimer values were normal (0.49 and 0.15 µg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody. CONCLUSIONS: The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.


Assuntos
Anticorpos Heterófilos/química , Anticorpos Heterófilos/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio , Imunoensaio/normas , Idoso , Idoso de 80 Anos ou mais , Anticorpos Heterófilos/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/química , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Imunoensaio/métodos , Reprodutibilidade dos Testes
4.
Mol Med Rep ; 11(4): 3134-42, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25483347

RESUMO

The expansion of CD4+ CD25+ forkhead box (FOX)P3+ regulatory T (Treg) cells has been observed in patients with Mycobacterium (M.) tuberculosis; however, the mechanism of expansion remains to be elucidated. The aim of the present study was to examine the role of the early secreted antigenic target 6(ESAT­6) and antigen 85 complex B (Ag85B) from M. tuberculosis on Treg cell expansion. To investigate the sensitivity of peripheral blood cultures to the M. tuberculosis ESAT­6 and Ag85B antigens, the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells was determined using flow cytometry and the levels of FOXP3 mRNA were determined using reverse transcription quantitative polymerase chain reaction. The mRNA levels of FOXP3 and the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells were increased in multiplicitous drug­resistant tuberculosis patients compared with those in healthy controls and patients with latent tuberculosis (TB) infection (LTBI) (P<0.001). The mycobacterial antigens ESAT­6 and Ag85B increased the expansion of the CD4+ CD25+ FOXP3+ Treg cells and the mRNA levels of FOXP3 in healthy controls and LTBI patients compared with the effect of Bacillus Calmette­Guerin (P<0.05). Additionally, the mRNA levels of FOXP3 were elevated in the LTBI patients following stimulations with the mycobacterial antigens (P=0.012). Therefore, the M. tuberculosis antigens ESAT­6 and Ag85B induced CD4+ CD25+ FOXP3+ Treg­cell expansion, particularly in patients with LTBI. These findings indicated that CD4+ CD25+ FOXP3+ Treg cells may have a primary role in the failure of the host immune system to eradicate M. tuberculosis.


Assuntos
Aciltransferases/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Tuberculose/imunologia , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Humanos , Imunofenotipagem , Tuberculose Latente/genética , Tuberculose Latente/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Fenótipo , RNA Mensageiro/genética , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Adulto Jovem
5.
Int J Infect Dis ; 14(9): e815-22, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20655262

RESUMO

OBJECTIVES: Immune regulatory mechanisms may limit the immunopathologic condition of infection with Mycobacterium tuberculosis and suppress cellular immune responses in the host. We investigated the CD4(+)CD25(+)FoxP3(+) circulating regulatory T cells (T(reg)) in patients with cavity multidrug-resistant tuberculosis (MDR-TB) before and after surgery. METHODS: We compared the proportion of T(reg) cells in 13 patients with cavity MDR-TB pre- and postoperatively and in 10 healthy control subjects by flow cytometry using three specific markers in peripheral blood lymphocytes: cell-surface CD4 and CD25 expression and intracellular FoxP3 expression. RESULTS: The proportion of CD4(+)CD25(high) and CD4(+)CD25(+)FoxP3(+) T(reg) was significantly higher in patients with cavity MDR-TB and at 1-month postoperatively than in healthy controls (p<0.001). The proportion of CD4(+) and CD4(+)CD25(-) cells was significantly lower in patients with cavity MDR-TB than in controls (p<0.001). Pre- and postoperative proportions of CD4(+)CD25(high) and CD4(+)CD25(+)FoxP3(+) T(reg) cells showed a positive correlation (r=0.878, p<0.001). CONCLUSION: Circulating T(reg) cells are increased in proportion in patients with cavity MDR-TB and decreased after surgery. Infection with M. tuberculosis may induce T(reg) cell-surface molecular changes with increased numbers of cells.


Assuntos
Antígenos CD4/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Pulmão/imunologia , Linfócitos T Reguladores/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Tuberculose Pulmonar/cirurgia , Adolescente , Adulto , Idoso , Feminino , Citometria de Fluxo , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Pneumonectomia/métodos , Radiografia , Linfócitos T Reguladores/citologia , Tomógrafos Computadorizados , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico por imagem , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
6.
Cancer Lett ; 274(1): 16-24, 2009 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-18829157

RESUMO

Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris. Here, we report that treatment with lycorine resulted in survival inhibition and apoptosis induction in human leukemia cell lines. Lycorine induced apoptosis in human leukemia cells via intrinsic mitochondria pathway and caused a rapid-turnover of protein level of Mcl-1 which occurred before caspases activation. Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was also observed in blasts from patients with acute myeloid leukemia. Our findings suggest that lycorine may be a good candidate therapeutic agent against leukemia in worth of further evaluation.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Apoptose/efeitos dos fármacos , Leucemia/metabolismo , Fenantridinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Western Blotting , Caspases/metabolismo , Citocromos c/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Leucemia/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Células Tumorais Cultivadas
7.
Planta Med ; 72(6): 501-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16773533

RESUMO

It is reported that matrine, one of the major effective compounds isolated from the root of Sophora flavescens Ait., has anti-leukemia activity. In this study, we find that the treatment of leukemia U937 cells with matrine results in induction of apoptosis. Analysis of the mechanism underling this apoptotic event showed activation of caspases-9, -3, and -7, and release of cytochrome C from mitochondria to cytosol, and cleavage of poly(ADP-ribose) polymerase. Matrine did not alter the level of bcl-2 and bcl-xL as well as bax. In addition, no correlation was found between matrine administration and activation of the three major MAPK subfamilies (Erk1/2, p38, JNK/SAPK). The results indicate that matrine induces apoptosis in U937 cells via a cytochrome C-triggered caspase activation pathway.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Fitoterapia , Quinolizinas/farmacologia , Sophora , Alcaloides/administração & dosagem , Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Relação Dose-Resposta a Droga , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Quinolizinas/administração & dosagem , Quinolizinas/uso terapêutico , Células U937/efeitos dos fármacos , Matrinas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA