RESUMO
Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.
Assuntos
Proteínas de Ligação a DNA/genética , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Esquistossomose mansoni/imunologia , Animais , Apoptose , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/imunologia , Modelos Animais de Doenças , Inflamassomos/imunologia , Inflamação , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Espécies Reativas de Oxigênio/imunologia , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologiaRESUMO
Objective: To investigate the relationship among depression, anxiety, stress and addictive substance use behavior in secondary vocational students. Methods: Cluster sampling method and the Adolescent Health-related Behaviors Questionnaire were used to collect demographic characteristics, psychological symptoms, and addictive substance usage among 5 935 students in nine vocational schools in Chongqing, Zhaoqing, Ningbo, and Taiyuan. Multivariate logistic regression analysis was used to analyze the relationship between the addictive substance use behavior and psychological factors. Results: The detection rates of depression, anxiety and stress were 46.5% (n=2 762), 58.7% (n=3 483), and 29.8% (n= 1 770), respectively. The prevalence of addictive substances was 74.8% (n=4 440), traditional drugs was 0.8% (n=50), new drugs was 2.8% (n=166), other addictive drugs was 4.1% (n=241). Multivariate logistic regression analysis showed that compared with the normal psychological states of secondary vocational students, the OR value of mild depression tendency alcohol and tobacco use behavior of secondary vocational students was 1.45; the OR values of mild anxiety, moderate anxiety, severe anxiety and very serious anxiety were 1.46, 1.46, 1.71, and 1.83, respectively; the traditional drugs use behaviors were 5.51, and 2.61, respectively, for the severe anxiety and very serious anxiety. Compared with the normal psychological state of secondary vocational students, the OR values of the severe anxiety and very severe anxiety were 2.56, and 2.66, respectively, for severe anxiety and very serious anxiety. Compared with normal psychological status of secondary vocational students, the OR values of mild, moderate, severe, and very severe anxiety were 2.14, 2.47, 2.39, and 3.45, respectively; all P values <0.05. Conclusion: Anxiety and mild depression were risk factors of tobacco and alcohol use in secondary vocational students; severe and above anxiety were the risk factors of drug use in secondary vocational students; anxiety was the risk factor for other addictive drug use in secondary vocational students.
Assuntos
Ansiedade , Depressão , Estresse Psicológico/epidemiologia , Estudantes/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Consumo de Bebidas Alcoólicas , Ansiedade/epidemiologia , China/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Características da Família , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Fatores de Risco , Estresse Psicológico/psicologia , Estudantes/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inquéritos e Questionários , Educação VocacionalRESUMO
A BaTiO3/SrCoO2.5 (BTO/SCO) bilayer and a BTO single film were prepared by radio frequency magnetron sputtering on La0.7Sr0.3MnO3 (LSMO) buffered SrTiO3 (001) substrates. Interestingly, compared with reported BTO-based films, the BTO/SCO/LSMO heterostructure has a maximum ON/OFF current ratio of â¼945. More interestingly, compared with the BTO single layer, a larger Pr (â¼18.4 µC cm-2) and larger dielectric tunability (â¼71.9%) were achieved in the BTO/SCO bilayer. The improved performance may be attributed to the large tetragonality and improved oxygen vacancy concentrations in the BTO/SCO/LSMO heterostructure. Furthermore, our BTO/SCO/LSMO stacks exhibit potential for flexible electronic informational devices.
RESUMO
With the rapid development of global tourism, traveling gradually becomes an important part of daily lives, and travelers'health is paid more and more attention. Traveler's diarrhea (TD) is one of the most common diseases among international or trans-regional travelers, which causes great disease and economic burdens. Currently, there is still a lack of systematic studies on the correlation between parasites and TD. The review mainly summarizes intestinal protozoa and helminth infections among patients with TD, so as to provide insights into the development of the control measures for parasitic diseases associated with TD and the prevention of risk factors before the journey to and during the journey of the areas endemic for parasitic diseases.
Assuntos
Diarreia , Doenças Parasitárias , Humanos , Doenças Parasitárias/epidemiologia , Fatores de Risco , ViagemRESUMO
Sj16, a 16-kDa protein produced by Schistosoma japonicum, has been demonstrated to have anti-inflammatory effect. However, the possible mechanism of these phenomena has not been discovered. Here, we tried to touch it with arthritis rats' model induced by injection of complete Freund's adjuvant (CFA). A set of pathogenic characters were observed in CFA-treated rat, including local and systematic read-out, which showed the model successfully set up. After administration of rSj16 (recombinant Sj16) in vivo, paw swelling reduced significantly and in a dose-dependent manner, the level of TNF-α, IL-1ß and NO decreased and IL-10 in the serum increased. In vitro, rSj16 reversed the augmented surface expression of CD80, CD86, CD54 and OX6 induced by lipopolysaccharide (LPS) in bone marrow-derived DCs (BMDCs), whereas endocytotic capacity of rSj16-treated dendritic cell (DC) was profoundly increased. IL-12p70 released from rSj16-treated BMDC was decreased but IL-10 increased. Further, following incubation with rSj16 primed BMDCs, the sensitized T cells exhibited increased production of anti-inflammatory IL-10 and IL-4 and decreased production of IL-12p70 and IFN-γ. Collectively, these results implied that rSj16 alleviated CFA-induced arthritis, and the possible mechanisms may be its interruption of maturation and function of DCs. rSj16 could be a potential therapeutic agent against rheumatoid arthritis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antígenos de Helmintos/administração & dosagem , Artrite Experimental/prevenção & controle , Produtos Biológicos/administração & dosagem , Adjuvante de Freund/toxicidade , Fatores Imunológicos/administração & dosagem , Schistosoma japonicum/química , Animais , Artrite Experimental/patologia , Citocinas/sangue , Relação Dose-Resposta a Droga , Mediadores da Inflamação/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagemRESUMO
Indoleamine 2, 3-dioxygenase (IDO) is an important immunoregulatory enzyme, which mediates immune effects by depleting tryptophan and producing multiple metabolites. Recently, the studies on the immune function of IDO have been mostly restricted in tumors and autoimmune diseases. Nevertheless, there are few studies pertaining to the role of IDO in parasitic diseases, notably in parasite-host immune interactions. This review mainly describes IDO-mediated immunoregulatory effects and its regulation of parasite-host interactions, so as to provide insights into the development of immune intervention schemes against parasitic diseases.
Assuntos
Doenças Autoimunes , Neoplasias , Parasitos , Animais , Indolamina-Pirrol 2,3,-Dioxigenase , TriptofanoRESUMO
OBJECTIVE: To investigate the dynamics changes of the myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells in mice infected with Echinococcus granulosus and explore the possible biological significance. METHODS: Thirty female BALB/c mice of 6 weeks old were randomly divided into the infection and control groups, of 15 mice in each group. Mice in the infection group were intraperitoneally injected with 2 000 E. granulosus protoscoleces, while those in the control group were injected with the same volume of physiological saline. Mouse liver white blood cells were harvested 3 (early stage), 6 (medium stage) and 12 months (late stage) post-infection, and the proportions of MDSCs, their subpopulations (M-MDSCs and PMN-MDSCs) and Treg cells were assessed by flow cytometry. RESULTS: The proportions of MDSCs were (1.61 ± 0.36)%, (5.68 ± 0.69)% and (16.18 ± 0.69)% in mouse liver white blood cells in the infection group 3, 6 and 12 months post-infection with E. granulosus, and (2.19 ± 0.42)%, (0.99 ± 0.07) % and (4.18 ± 0.84)% in the control group, and there were significant differences in the proportion of the MDSCs in mouse liver white blood cells between the infection and control groups 6 and 12 months post-infection (P < 0.01). The proportions of M-MDSCs were (0.69 ± 0.27)%, (5.30 ± 0.72)% and (10.75 ± 0.29)% in mouse liver white blood cells in the infection group 3, 6 and 12 months post-infection, and (0.42 ± 0.24)%, (0.69 ± 0.02)% and (2.12 ± 0.13)% in the control group, and there were significant differences in the proportion of the M-MDSCs in the mouse liver white blood cells between the infection and control groups 6 and 12 months post-infection (P < 0.01). The proportions of PMN-MDSCs were (0.93 ± 0.23)%, (0.32 ± 0.02)% and (5.14 ± 1.03)% in mouse liver white blood cells in the infection group 3, 6 and 12 months post-infection, and (1.77 ± 0.26)%, (0.28 ± 0.05)% and (1.99 ± 0.90)% in the control group, and there were significant differences in the proportion of PMN-MDSCs in mouse liver white blood cells between the infection and control groups 3 and 12 months post-infection (P < 0.05). The proportions of Treg cells were (3.35 ± 0.14)%, (6.24 ± 0.38)% and (3.41 ± 0.07)% in mouse liver white blood cells in the infection group 3, 6 and 12 months post-infection, and (3.48 ± 0.46)%, (3.65 ± 0.45)% and (3.12 ± 0.12)% in the control group, and there were significant differences in the proportion of Treg cells in mouse liver white blood cells between the infection and control groups 6 and 12 months post-infection (P < 0.01). CONCLUSIONS: The percentages of both MDSCs and Treg cells increase in mouse liver white blood cells 6 and 12 months post-infection with E. granulosus, and a more remarkable increase is seen in the percentage of MDSCs, which is mainly found in M-MDSCs. These findings suggest that M-MDSCs may play a major immunosuppressive role in the medium and late stages of E. granulosus infection in mice.
Assuntos
Equinococose , Echinococcus granulosus , Fígado , Células Supressoras Mieloides , Linfócitos T Reguladores , Animais , Equinococose/imunologia , Echinococcus granulosus/imunologia , Feminino , Fígado/imunologia , Fígado/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/imunologia , Distribuição Aleatória , Linfócitos T Reguladores/imunologiaRESUMO
SETTING: The tuberculosis component of the Infectious and Endemic Disease Control Project in the People's Republic of China is the largest single tuberculosis control project in the world using directly-observed therapy and standardized intermittent regimens. OBJECTIVE: To determine the two-year relapse and mortality rates following completion of treatment. DESIGN: A prospective cohort study of 649 cases cured in this project. The 306 new and 343 retreatment cases were treated under field conditions with 2H3R3Z3S3/4H3R3 and 2H3R3Z3E3S3/6H3R3E3, respectively. Following treatment completion, two sputum samples were collected every six months for two years and examined for acid-fast bacilli. Causes of death were identified. RESULTS: The two-year relapse rates for new and retreatment cases were 3.3% and 5.6%, respectively. Retreatment cases with delayed sputum conversion had a greater risk for subsequent relapse. The two-year mortality rate for new and retreatment cases was 3.3% and 8.5%, respectively. The higher mortality rate in retreatment cases was not attributable to relapse of disease, but rather to non-infectious sequelae of tuberculosis. CONCLUSION: The use of directly-observed intermittent regimens is effective in permanently removing infectious tuberculosis cases from the community.
Assuntos
Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Causas de Morte , China , Seguimentos , Humanos , Mycobacterium tuberculosis/isolamento & purificação , Recidiva , Escarro/microbiologia , Análise de Sobrevida , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/prevenção & controleRESUMO
There is evidence that immunoglobulin (Ig) E antibody may be a critical component of protective immunity against Schistosoma mansoni and S. haematobium reinfection. In the present study, 555 individuals aged 3-67 years infected with S.japonicum received praziquantel treatment before the transmission season commenced; 45 d later, blood samples from 265 individuals who had no S. japonicum egg in their stool were examined by enzyme-linked immunosorbent assay for specific isotypic antibodies. Single, non-conditional logistic regression analysis showed that exposure intensity, age, soluble egg antigen (SEA)-IgE, SEA-IgM and soluble adult worm antigen-IgG4 were relevant to reinfection; multiple, non-conditional logistic regression analysis showed that exposure intensity was still a significant factor for reinfection while the SEA-IgE antibody level was associated with resistance to reinfection with S. japonicum, with a protective index of 2.00. It is suggested that this population in an area endemic for schistosomiasis japonica exhibits acquired immunity.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Imunoglobulina E/sangue , Esquistossomose Japônica/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Antiplatelmínticos/uso terapêutico , Criança , Pré-Escolar , China , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Modelos Logísticos , Pessoa de Meia-Idade , Praziquantel/uso terapêutico , Recidiva , Esquistossomose Japônica/tratamento farmacológicoRESUMO
OBJECTIVE: To clone and express the cDNA encoding Schistosoma japonicum tropomyosin. METHODS: The cDNA was amplified by reverse transcription-polymerase chain reaction (RT-PCR). The PCR products were ligated with pGEM-T vectors and then for transformations. After characterization of white clones by agarose gel electrophoresis, endonucleases digestion and PCR, some recombinant plasmids with inserts were used for sequencing. Then the gene was subcloned into prokaryotic expression vector pQE30 and expression was induced by IPTG. RESULTS: The PCR products was 823 bp judged by agarose gel electrophoresis and sequencing. A cDNA encoding S. japonicum tropomyosin, except for 14 amino acids at the amino terminus and 2 at the carboxyl terminus, has been constructed and cloned successfully. The colony, designated pGSjcTM12, was sequenced and shown to be 91.1% identical at the nuclei acid level and 98.1% identical in deduced amino acid sequence to that of S. mansoni tropomyosin. The gene was subcloned into pQE30 and an expressed protein of about 32 kDa was obtained. CONCLUSION: The cloning and expression of the gene encoding S. japonicum tropomyosin had been successfully made.
Assuntos
Proteínas Recombinantes/biossíntese , Schistosoma japonicum/genética , Tropomiosina/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , DNA Complementar/química , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Tropomiosina/biossínteseRESUMO
Hypoxia or hypoxia mimetic has been shown to induce differentiation together with the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein of myeloid leukemic cells and normal hematopoietic progenitors. To provide direct evidence for the role of HIF-1alpha in acute myeloid leukemia (AML) cell differentiation and its mechanisms, we generated myeloid leukemic U937T transformants, in which HIF-1alpha was tightly induced by tetracycline withdrawal. The results showed that the conditional HIF-1alpha induction triggered granulocytic differentiation of these transformants, while the suppression of HIF-1alpha expression by specific short hairpin RNAs (shRNAs) effectively inhibited hypoxia-induced differentiation of U937 cells, as evidenced by morphology, maturation-related antigens as well as expressions of myeloid differentiation signatures and hematopoietic cells-specific cytokine receptors. The specific shRNAs-inhibited expression of HIF-1beta, an essential partner for transcription activity of HIF-1, failed, while the inhibition of hematopoietic differentiation-critical CCAAT/enhancer-binding protein-alpha (C/EBPalpha) significantly eliminated HIF-1alpha-mediated myeloid leukemic cell differentiation. Collectively, this work provided several lines of direct evidence for the role of HIF-1alpha protein through its nontranscriptional activity in myeloid cell differentiation, in which C/EBPalpha elicits a role as an effector downstream to HIF-1alpha. These discoveries would shed new insights for understanding mechanisms underlying leukemogenesis and designing the new therapeutic strategy for differentiation induction of AML.
Assuntos
Diferenciação Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Leucemia Mieloide/patologia , Ativação Transcricional/fisiologia , Proteínas Estimuladoras de Ligação a CCAAT/fisiologia , Hipóxia Celular/fisiologia , Proliferação de Células , Células Cultivadas , Fatores Estimuladores de Colônias/metabolismo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Leucemia Mieloide/genética , RNA Interferente Pequeno/farmacologia , Transfecção , Células U937RESUMO
The TEL1 gene from Saccharomyces cerevisiae has been shown to be the closest sequence homologue to ATM, the gene mutated in ataxia-telangiectasia (A-T) patients. Functional homology shared between the ATM and Tell proteins has recently been demonstrated based on heterologous expression of the TEL1 gene in human cells derived from A-T patients. TEL1 expression complemented specific cellular A-T deficiencies, i.e. increased radiation-induced apoptosis, telomere shortening and spontaneous hyperrecombination. The mechanism of cellular A-T complementation by TEL1 appears to be independent of p53-dependent signaling cascades, since the deficiency of A-T cells to properly induce p53 upon ionizing radiation was not corrected by TEL1. We now find that the basic number of chromosome aberrations is increased and the number of radiation-induced chromosome aberrations is suppressed in A-T cells upon TEL1 expression. In cell cycle analyses, we find no changes in basic cell cycle distribution or in radiation-induced cell cycle checkpoints following TEL1 expression. We conclude that the radioprotective function of the Tel1 protein includes suppression of apoptosis and suppression of chromosome aberrations, and that both cellular end-points can be uncoupled from ionizing radiation-induced cell cycle checkpoints.
Assuntos
Ataxia Telangiectasia/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/fisiologia , Mutação , Saccharomyces cerevisiae/metabolismo , Ataxia Telangiectasia/metabolismo , Ciclo Celular , Aberrações Cromossômicas , Relação Dose-Resposta à Radiação , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Genéticos , Fenótipo , Proteínas Serina-Treonina Quinases , Proteínas de Saccharomyces cerevisiae , Transdução de Sinais , Fatores de Tempo , TransfecçãoRESUMO
AIM: To study the distribution of NADPH-diaphorase positive neurons in periaqueductal gray matter(PAG) and dorsal raphe nucleus (DR), and the correlation between nitric oxide and peripheral nociception at supraspinal level. METHODS: 20 Sprague-Dawley rats were randomly divided into two groups. In experimental group (n = 10), formalin (5%, 0.1 ml) was injected subcutaneously into the plantar surface of the unilateral hindpaw, and in control group (n = 10), normal saline solution was used alike. The rats were perfused after 2 hours, and the midbrain were removed. Frozen seriate transverse sections were divided into three sets, all of which were processed for NADPH-d histochemistry. Subsequently, the first set that contained NADPH-diaphorase positive neurons were stained with neutral red, and the other two sets were processed for c-fos immunohistochemistry. RESULTS: NADPH-diaphorase positive neurons were densely distributed in CGLD, CGLV and DR. NADPH-d, Fos and NADPH/Fos double-labeled neurons appeared in CGLD, CGLV and DR after injection of formalin in the rat hindpaw. CONCLUSION: At supraspinal level NO may play an important role in the modulation of nociception in PAG and DR.