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1.
Clin Exp Rheumatol ; 34(6 Suppl 102): 111-114, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27791954

RESUMO

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.


Assuntos
Síndrome de Behçet/epidemiologia , Oftalmopatias/epidemiologia , Hipersensibilidade/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Comorbidade , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
2.
Environ Sci Technol ; 50(9): 4632-41, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27050081

RESUMO

Haze episodes occurred in Beijing repeatedly in 2013, resulting in 189 polluted days. These episodes differed in terms of sources, formation processes, and chemical composition and thus required different control policies. Therefore, an overview of the similarities and differences among these episodes is needed. For this purpose, we conducted one-year online observations and developed a program that can simultaneously divide haze episodes and identify their shapes. A total of 73 episodes were identified, and their shapes were linked with synoptic conditions. Pure-haze events dominated in wintertime, whereas mixed haze-dust (PM2.5/PM10 < 60%) and mixed haze-fog (Aerosol Water/PM2.5 ∼ 0.3) events dominated in spring and summer-autumn, respectively. For all types, increase of ratio of PM2.5 in PM10 was typically achieved before PM2.5 reached ∼150 µg/m(3). In all PM2.5 species observed, organic matter (OM) was always the most abundant component (18-60%), but it was rarely the driving factor: its relative contribution usually decreased as the pollution level increased. The only OM-driven episode observed was associated with intensive biomass-burning activities. In comparison, haze evolution generally coincided with increasing sulfur and nitrogen oxidation ratios (SOR and NOR), indicating the enhanced production of secondary inorganic species. Applicability of these conclusions required further tests with simultaneously multisite observations.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Aerossóis , Pequim , China
3.
Talanta ; 260: 124616, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146457

RESUMO

For applying highly sensitive mass spectrometry to chemical analysis of aqueous samples, we have developed a novel technique using a new form of liquid droplets, which we call "aeromicelle" (AM), to deliver aqueous sample solutions directly into the vacuum region of a single-particle mass spectrometer in liquid form and conduct immediate mass analysis. AMs are generated by spraying an aqueous solution containing a surfactant at a concentration significantly lower than its critical micelle concentration (CMC). When the solution is sprayed, liquid droplets containing the surfactant are formed, which gradually dry in an air flow. Upon drying, the surfactant concentration in the droplet exceeds its CMC, and consequently, the surfactant molecules begin to cover the droplet surface. Finally, the surface is expected to be fully covered with surfactant molecules such as reverse micelles. The surface coverage helps suppress the evaporation of water, thereby enhancing the residence time of the liquid droplet. Our experimental results show that the AMs retained a liquid form for at least 100 s in air and survived even under vacuum conditions for further mass analysis: each AM delivered in the vacuum region of a single-particle mass spectrometer is ablated with an intense laser pulse and then, mass analyzed. Individual AMs generated from an aqueous solution containing CsCl were analyzed using a single-particle mass spectrometer. The Cs+ ion peak was observed even in AMs generated from the 10 nM solution. The number of Cs atoms in each AM was estimated to be approximately 7 × 103, which corresponds to 1.2 × 10-20 mol (12 zmol). Meanwhile, in the mass analysis of tyrosine, both positive and negative fragmentation ions from tyrosine in AMs were observed in the mass spectrum and 4.6 × 105 (760 zmol) tyrosine molecules were detected.

4.
Nutrients ; 15(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36771462

RESUMO

Food allergy is one of the major existing health problems, but no effective treatment is available. In the current work, a murine model that closely mimics pathogenesis of human food allergy and its quantifiable diagnostic parameter design, even for mild hypersensitivity reactions, were established. BALB/c mice were epicutaneously sensitized with 1 mg chicken egg ovomucoid (OVM) or cow's milk casein, free of adjuvants, five times a week for two consecutive weeks. Eleven days later, allergen-specific IgG1 and IgE in serum were measured by ELISA. On day 25, 20 mg OVM or 12 mg α-casein was administered orally, and allergic reactions such as the fall in rectal temperature, symptom scores during 90-120 min, serum mast cell protease-1 and cytokine levels were monitored. The detection of mild allergic reactions due to adjuvant-free allergen sensitization and oral allergen challenge routes was amplified by the combination of oral allergen and aspirin administration simultaneously or aspirin administration within 15-30 min before an allergen challenge. Quantification of the maximum symptom score and the frequency of symptoms during the monitoring period improved evaluation accuracy of food allergy signals. Based on these results, efficacy of casein oral immunotherapy for cow's milk allergies, which are generally difficult to detect, was monitored adequately.


Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Humanos , Feminino , Bovinos , Camundongos , Animais , Alérgenos , Caseínas , Aspirina , Modelos Animais de Doenças , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Adjuvantes Imunológicos , Ovomucina , Imunoterapia
5.
Influenza Other Respir Viruses ; 17(3): e13119, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36909295

RESUMO

Background: There is a need for vaccines that can induce effective systemic, respiratory mucosal, and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA, and cellular immunity. Methods: The aim of the present study was to determine the effectiveness of a new administration route of trans-airway (TA) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local, and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AddaS03™ (S1-AddaS03™ vaccine). Results: S1-SF-10-TA vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-TA showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AddaS03™-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AddaS03™-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF-10-TA, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusions: Based on the need for effective systemic, respiratory, and cellular immunity, the S1-SF-10-TA vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.


Assuntos
COVID-19 , Surfactantes Pulmonares , Humanos , Animais , Camundongos , Surfactantes Pulmonares/farmacologia , SARS-CoV-2 , Interleucina-4/farmacologia , Pandemias , Imunidade nas Mucosas , Anticorpos Antivirais , Adjuvantes Imunológicos , Imunidade Celular , Imunoglobulina A/farmacologia , Imunoglobulina G
6.
Environ Pollut ; 322: 121154, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36736562

RESUMO

Air quality has significantly improved in China; however, new challenges emerge when dust weather is combined with haze pollution during spring in northern China. On March 15, 2021, an extremely severe sandstorm occurred in Beijing, with hourly maximum PM10 and PM2.5 concentrations reaching 5267.7 µg m-3 and 963.9 µg m-3, respectively. Continuous sandstorm events usually lead to complicated pollution status in spring. Three pollution types were identified disregarding the time sequence throughout March. The secondary formation type was dominant, with high ratios of PM2.5/PM10 (mean 74%) and PM1/PM2.5 (mean 52%). This suggests that secondary transformations are the primary cause of heavy pollution, even during the dry seasons. Sandstorm type resulted in dramatic PM10 levels, with a noticeable decrease in PM2.5/PM10 levels (27%), although PM2.5 levels remain high. The transitional pollution type was distinguished by an independent increase in PM10 levels, although PM2.5 and PM1 levels differed from the PM10 levels. Throughout March, the sulfur oxidation rate varied considerably, with high levels during most periods (mean 0.52). A strong correlation indicated that relative humidity was the primary variable promoting the formation of secondary sulfate. Sandstorms promote heterogeneous reactions by providing abundant reaction surfaces from mineral particles, therefore aggravating secondary pollution. The sandstorm air mass from the northwest passing through the sand sources of Mongolia carried not only crustal matter but also organic components, such as bioaerosols, resulting in a sharp increase in the organic carbon in PM2.5.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pequim , Poluentes Atmosféricos/análise , Material Particulado/análise , Monitoramento Ambiental , China , Estações do Ano , Aerossóis/análise
7.
Viruses ; 15(8)2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37632005

RESUMO

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen-antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6-8 months regardless of the subsequent change in the antibody levels.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Anticorpos Antivirais
8.
Environ Pollut ; 318: 120846, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36496065

RESUMO

Organic aerosols (OA) are major components of fine particulate matter, yet their formation mechanism remains unclear, especially in polluted environments. In this study, we investigated the diurnal chemical compositions and formation processes of OA in carbonaceous particles during winter in Beijing using aerosol time-of-flight mass spectrometry. We found that 84.5% of the measured carbonaceous particles underwent aging processes, characterized by larger diameter and more secondary species compared to fresh carbonaceous particles, and presented different chemical compositions of OA in the daytime and nighttime. During the day, under high O3 concentrations, organosulfates and oligomers existed in the aged carbonaceous particles, which were mixed with a higher signal of nitrate compared with sulfate. At night, under high relative humidity, distinct spectral signatures of hydroxymethanesulfonate and organic nitrogen compounds, and minor signals of other hydroxyalkylsulfonates and high molecular weight organic compounds were present in the aged carbonaceous particles, which were mixed with a higher signal of sulfate compared with nitrate. Our results indicated that photochemistry contributed to OA formation in the daytime, while aqueous chemistry played an important role in OA formation in the nighttime. The findings can help improve the performance of air quality and climate models on OA simulation.


Assuntos
Poluentes Atmosféricos , Pequim , Poluentes Atmosféricos/análise , Nitratos/análise , Monitoramento Ambiental , Material Particulado/análise , Compostos Orgânicos/análise , Estações do Ano , Aerossóis/análise , Sulfatos/análise , China
9.
Vaccine ; 40(3): 544-553, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34887132

RESUMO

A safe and effective mucosal adjuvant is required for vaccination against influenza A virus (IAV) infection. Previously, we described that intranasally administration of surfacten®, a medicine derived from bovine pulmonary surfactant (PS), with IAV vaccine can induce IAV-specific IgA in the respiratory tract mucosa and IgG in serum. PS is secreted by alveolar type II cells and Clara cells and serves to reduce lung surface tension. PS finished its rules is incorporated by antigen presenting cells (APCs), such as alveolar macrophages and dendritic cells, and alveolar type II cells and rapidly metabolized. We focused on the metabolic pathways and rapid metabolic turnover of PS and developed a PS-based mucosal adjuvant. First, we determined the essential components of PS adjuvanticity and found that the complex of three PS lipids and surfactant protein-C can enhance to deliver the vaccine antigen and activate APCs. Later, we improved the safety, efficacy and ease of manufacture and finally succeeded in developing SF-10. The use of SF-10 with influenza split vaccine (HAv) (HAv-SF-10) enhances HAv incorporation into APCs both in vitro and in vivo, and intranasal instillation of HAv-SF-10 induced systemic and mucosal HAv-specific immunities in not only mice but also cynomolgus monkeys. The report that PS has physiological effects on the gastrointestinal mucosa prompted us develop a new SF-10-based vaccine that can be administered orally. In this review, We summarize our work on the development of clinically effective PS-based nasal and oral mucosal adjuvants for influenza vaccine.


Assuntos
Vacinas contra Influenza , Surfactantes Pulmonares , Adjuvantes Imunológicos , Administração Intranasal , Animais , Anticorpos Antivirais , Humanos , Imunidade nas Mucosas , Redes e Vias Metabólicas , Camundongos , Camundongos Endogâmicos BALB C , Mucosa
10.
Sci Total Environ ; 817: 152981, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35026267

RESUMO

Microplastic (MP) pollution in the aquatic environment is a cause for increasing concern. However, analyzing MPs ingested by small organisms, such as zooplankton, is difficult because of the low content and small size of the ingested MPs. We attempted to determine the content of ingested MPs in individual zooplankton using pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). To establish zooplankton model of MP ingestion, individual Daphnia magna were cultivated separately in microplate cells with polystyrene (PS) microspheres (10 µm in diameter, 245,000 particles, 135 µg) under different conditions. To prepare calibration curves for determining ingested PS content, approximately 100-150 µg of commercially available Daphnia-based powdered fish food, roughly corresponding to the weight of a single D. magna organism, was mixed with PS microspheres (0.005-26 µg) and analyzed using Py-GC-MS at 600 °C. In the resulting pyrograms, peaks of the styrene monomer and trimer from PS were detected, and linear relationships were obtained between the relative peak area and the amount of added PS. Finally, the cultivated zooplankton were individually subjected to Py-GC-MS analysis, and the ingested PS content in each zooplankton was successfully determined. Individual zooplankton cultured with PS in the absence of food ingested 2.3-7.9 µg of PS particles, whereas that in the presence of food (Chlorella vulgaris) ingested only 0.1-0.2 µg of PS particles. This result suggests that zooplankton might preferentially ingest ordinary food when both food and MPs are present, although further systematic studies are necessary to validate this observation.


Assuntos
Chlorella vulgaris , Poluentes Químicos da Água , Animais , Daphnia , Cromatografia Gasosa-Espectrometria de Massas , Microesferas , Plásticos , Poliestirenos/análise , Pirólise , Poluentes Químicos da Água/análise
11.
Chemosphere ; 286(Pt 2): 131807, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34371362

RESUMO

An online field observation was conducted in Zibo, China from September 1, 2018 to February 28, 2019, covering autumn and winter. Within the investigation period, the mean mass concentrations of PM1, PM2.5, and PM10 were 49.3, 86.1, and 136.5 µg m-3, respectively. OA (organic aerosol) was the most dominant species in PM2.5 (39.7 %), followed by NO3- (26.3 %) and SO42- (17.0 %), indicating the importance of secondary species on PM2.5. Increase of particles were always accompanied increasing relative humidity (RH), slow wind, and increasing precursors, contributing the secondary transition. SO42- was more susceptible to RH, indicating the dominant role of heterogeneous processes in its secondary formation. As RH increased, its strengthening effect on SO42- increased as well. Photochemistry was the main contributor to the secondary formation of NO3-. The morning and evening rush hours determined the peak of absolute NO3- throughout the day. By classifying particles into three bins, we found that smaller particles were the biggest contributors (larger PM1/PM2.5) of slight pollution (35 < PM2.5<115 µg m-3). When severe haze occurred, PM2.5 contributed more than particles of other sizes (PM1 or PM10). Secondary species contributed more to particles within 2.5 µm but less to larger particles. PM1/PM2.5 was high from 9:00 to 15:00, indicating the strong effect of photochemistry on smaller particles. In comparison, larger particles favored more humid conditions. NO3- preferentially existed in larger particles because the hygroscopicity of preexisting species (SO42- and NO3-) promoted partitioning. SO42- appeared a stable diurnal variation, replying its stable contribution to particles of different sizes.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano
12.
Environ Pollut ; 279: 116923, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33751950

RESUMO

To control the spread of COVID-19, China implemented a series of lockdowns, limiting various offline interactions. This provided an opportunity to study the response of air quality to emissions control. By comparing the characteristics of pollution in the summers of 2019 and 2020, we found a significant decrease in gaseous pollutants in 2020. However, particle pollution in the summer of 2020 was more severe; PM2.5 levels increased from 35.8 to 44.7 µg m-3, and PM10 increased from 51.4 to 69.0 µg m-3 from 2019 to 2020. The higher PM10 was caused by two sandstorm events on May 11 and June 3, 2020, while the higher PM2.5 was the result of enhanced secondary formation processes indicated by the higher sulfate oxidation rate (SOR) and nitrate oxidation rate (NOR) in 2020. Higher SOR and NOR were attributed mainly to higher relative humidity and stronger oxidizing capacity. Analysis of PMx distribution showed that severe haze occurred when particles within Bin2 (size ranging 1-2.5 µm) dominated. SO42-(1/2.5) and SO42-(2.5/10) remained stable under different periods at 0.5 and 0.8, respectively, indicating that SO42- existed mainly in smaller particles. Decreases in NO3-(1/2.5) and increases in NO3-(2.5/10) from clean to polluted conditions, similar to the variations in PMx distribution, suggest that NO3- played a role in the worsening of pollution. O3 concentrations were higher in 2020 (108.6 µg m-3) than in 2019 (96.8 µg m-3). Marked decreases in fresh NO alleviated the titration of O3. Furthermore, the oxidation reaction of NO2 that produces NO3- was dominant over the photochemical reaction of NO2 that produces O3, making NO2 less important for O3 pollution. In comparison, a lower VOC/NOx ratio (less than 10) meant that Beijing is a VOC-limited area; this indicates that in order to alleviate O3 pollution in Beijing, emissions of VOCs should be controlled.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Gases , Humanos , Material Particulado/análise , SARS-CoV-2 , Estações do Ano
13.
Sci Total Environ ; 711: 134745, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822400

RESUMO

In the Northern China Plain (NCP), extreme haze events with high concentrations of fine particles occur frequently during the winter but rarely occur in autumn. In this study, we present a synthetic analysis of particulate constituents during the historically polluted transition period of autumn-winter in 2018, revealing that mixed-type haze episodes are the result of regional transport, homogeneous/heterogeneous conversion, and sandstorm influences. The hydrolysis process of N2O5 at higher relative humidity levels (>70%), which feature an enhanced nitrate oxidation ratio (0.30-0.70) and NO3- concentration (>60 µg m-3), was the driving factor for high PM2.5 mass concentrations during the observation periods. The long-distance transport of sandstorms, characterized by decreasing PM2.5/PM10 ratios (<30%) from the north/northwest, is the most important factor for the explosive growth of PM10 concentration. These results can help us gain a comprehensive understanding of haze formation and highlight the importance of nitrate chemistry in the aqueous phase. The results suggest that persistent NOx emission reduction measures must be made to better achieve air quality standards in Beijing and the NCP region.

14.
Sci Total Environ ; 746: 141209, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763608

RESUMO

Organic aerosols (OA) undergo sophisticated physiochemical processes in the atmosphere, playing a crucial role in extreme haze formations over the Northern China Plain. However, current understandings of the detailed composition and formation pathways are limited. In this study, high-molecular weight (HMW) species were observed in samples collected year-round in urban Beijing, especially in autumn and winter, during 2016-2017. The positive-ion-mode mass spectra of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) showed that higher signal intensities were obtained in the mass-to-charge (m/z) ranges of 200-500 and 800-900, with repetitive mass difference patterns of m/z 12, 14, 16, and 18. This provided sound evidence that high-molecular-weight oligomers were generated as haze episodes became exacerbated. These oligomer signal intensities were enhanced in the presence of high relative humidity, aerosol water content, and PM2.5 (particles with an aerodynamic diameter ≤ 2.5 µm) mass, proving that the multiphase reaction processes play a fundamental role in haze formation in Beijing. Our study can form a basis for improved air pollution mitigation measures aimed at OA to improve health outcomes.

15.
Biochimie ; 166: 203-213, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518617

RESUMO

Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A , Influenza Humana , Serina Proteases/fisiologia , Internalização do Vírus/efeitos dos fármacos , Animais , Galinhas/virologia , Citocinas/metabolismo , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/patogenicidade , Influenza Aviária/tratamento farmacológico , Influenza Aviária/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Tripsina/metabolismo
16.
Vaccine ; 37(4): 612-622, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30553569

RESUMO

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunidade nas Mucosas , Infecções por Orthomyxoviridae/prevenção & controle , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/imunologia , Administração Intranasal , Administração Oral , Animais , Anticorpos Antivirais/sangue , Citocinas/imunologia , Feminino , Humanos , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Surfactantes Pulmonares/química , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Vacinação/métodos
17.
Environ Pollut ; 244: 84-92, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30326389

RESUMO

Organic aerosol (OA) are always the most abundant species in terms of relative proportion to PM2.5 concentration in Beijing, while in previous studies, poor link between carbonaceous particles and their gaseous precursors were established based on field observation results. Through this study, we provided a comprehensive analysis of critical carbonaceous species in the atmosphere. The concentrations, diurnal variations, conversions, and gas-particle partitioning (F-factor) of 8 carbonaceous species, carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), volatile organic compounds (VOCs), non-methane hydrocarbon (NMHC), organic carbon (OC), elemental carbon (EC), and water soluble organic compounds (WSOCs), in Beijing were analyzed synthetically. Carbonaceous gases (CO, CO2, VOCs, and CH4) and OC/EC ratios exhibited double-peak diurnal patterns with a pronounced midnight peak, especially in winter. High correlation between VOCs and OC during winter nighttime indicated that OC was formed from VOCs precursors via an unknown mechanism at relative humidity greater than 50% and 80%, thereby promoting WSOC formation in PM1 and PM2.5 respectively. The established F-factor method was effective to describe gas-to-particle transformation of carbonaceous species and was a good indicator for haze events since high F-factors corresponded with enhanced PM2.5 level. Moreover, higher F-factors in winter indicated carbonaceous species were more likely to exist as particles in Beijing. These results can help gain a comprehensive understanding of carbon cycle and formation of secondary organic aerosols from gaseous precursors in the atmosphere.


Assuntos
Poluentes Atmosféricos/análise , Carbono/análise , Monitoramento Ambiental/métodos , Umidade , Compostos Orgânicos/análise , Material Particulado/análise , Estações do Ano , Aerossóis/análise , Poluição do Ar , Atmosfera/análise , Pequim , Ciclo do Carbono , Dióxido de Carbono/análise , Monóxido de Carbono/análise , China , Metano/análise , Tamanho da Partícula , Compostos Orgânicos Voláteis/análise , Água/análise
18.
Environ Pollut ; 253: 377-383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325882

RESUMO

Changzhou, an industrial city in the Yangtze River Delta, has been experiencing serious haze pollution, particularly in winter. However, studies pertaining to the haze in Changzhou are very limited, which makes it difficult to understand the characteristics and formation of winter haze in this area, and develop effective control measures. In this study, we carried out continuous online observation of particulate matter, chemical components, and meteorology in Changzhou in February 2017. Our results showed that haze pollution occurred frequently in Changzhou winter and exhibited two patterns: dry haze with low relative humidity (RH) and wet haze with high RH. Water-soluble inorganic ions (SO42-, NO3-, and NH4+) accounted for ∼52.2% of the PM2.5 mass, of which sulfate was dominant in wet haze periods while nitrate was dominant in other periods. With the deterioration of haze pollution, the proportion of nitrate in PM2.5 increased, while sulfate proportion increased under wet haze and decreased under dry haze. Dry haze and wet haze appeared under slow north wind and south wind, respectively, and strong north wind or sea breeze scavenged pollution. We found that formation of nitrate occurred rapidly in daytime with high concentrations of odd oxygen (Ox = O3 + NO2), whereas formation of sulfate occurred rapidly during nighttime with high RH, indicating that photochemistry and heterogeneous reaction were the major formation mechanisms for nitrate and sulfate, respectively. Through the cluster analysis of 36-h backward trajectories, five sources of air masses from three directions were identified. High PM2.5 concentrations (84.1 µg m-3 on average) usually occurred under the influence of two clusters (46%) from the northwest, indicating that regional transport from northern China aggravated the winter haze pollution in Changzhou. Emission reduction, particularly the mobile sources, and regional joint prevention and control can help to mitigate the winter haze in Changzhou.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , China , Cidades , Umidade , Meteorologia , Nitratos/análise , Óxidos de Nitrogênio/análise , Rios , Estações do Ano , Sulfatos/análise , Vento
19.
J Mass Spectrom ; 43(12): 1664-72, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18563852

RESUMO

Halohydrination of epoxy resins using sodium halides as cationizing agents in matrix-assisted laser desorption/ionization (MALDI) and desorption ionization on porous silicon mass spectrometry (DIOS-MS) were investigated. Different mass spectra were observed when NaClO(4) and NaI were used as the cationizing agents at the highest concentration of 10.0 mM, which is much higher than that normally used in MALDI-MS. MALDI mass spectra of epoxy resins using NaI revealed iodohydrination to occur as epoxy functions of the polymers. The halohydrination also occurred using NaBr, but not NaCl, due to the differences in their nucleophilicities. On the basis of the results of experiments using deuterated CD(3)OD as the solvent, the hydrogen atom source was probably ambient water or residual solvent, rather than being derived from matrices. Halohydrination also occurred with DIOS-MS in which no organic matrix was used; in addition, reduction of epoxy functions was observed with DIOS. NaI is a useful cationizing agent for changing the chemical form of epoxy resins due to iodohydrination and, thus, for identifying the presence of epoxy functions.

20.
PLoS One ; 13(1): e0191133, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370185

RESUMO

We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a model antigen, combined with SF-10 efficiently delivered antigen to mucosal dendritic and epithelial cells and promoted cross-presentation in antigen presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and upregulated granzyme B expression in splenic CD8+ T cells with their high cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes-mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of influenza virus infection compared with HAv alone. Protective immunity induced by HAv-SF-10 against lethal influenza virus infection was partially and predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by intraperitoneal injection of the corresponding antibodies), respectively, suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute to the protective immunity in the advanced stage of influenza virus infection. These results suggest that SF-10 promotes effective antigen delivery to antigen presenting cells, activates CD8+ T cells via cross-presentation, and induces cell-mediated immune responses against antigen.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Hemaglutinação por Vírus/imunologia , Imunidade Celular , Vacinas contra Influenza/administração & dosagem , Mimetismo Molecular , Surfactantes Pulmonares/química , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Vacinas contra Influenza/imunologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mucosa Nasal/imunologia
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