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BACKGROUND: Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy). METHODS: Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO). RESULTS: Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years). CONCLUSION: Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers.
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Asma , Humanos , Asma/epidemiología , Asma/genética , Asma/diagnóstico , Femenino , Masculino , Niño , Preescolar , Factores de Riesgo , Estudios Longitudinales , Metilación de ADN , Biomarcadores , Cohorte de NacimientoRESUMEN
BACKGROUND: Growing up on traditional farms protects children from the development of asthma and allergies. However, we have identified distinct asthma-protective factors, such as poultry exposure. This study aims to examine the biological effect of rural exposure in China. METHODS: We recruited 67 rural children (7.4 ± 0.9 years) and 79 urban children (6.8 ± 0.6 years). Depending on the personal history of exposure to domestic poultry (DP), rural children were further divided into those with DP exposure (DP+ , n = 30) and those without (DP- , n = 37). Blood samples were collected to assess differential cell counts and expression of immune-related genes. Dust samples were collected from poultry stables inside rural households. In vivo activities of nasal administration of DP dust extracts were tested in an ovalbumin-induced asthma model. RESULTS: There was a stepwise increase in the percentage of eosinophils (%) from rural DP+ children (median = 1.65, IQR = [1.28, 3.75]) to rural DP- children (3.40, [1.70, 6.50]; DP+ vs. DP- , p = .087) and to the highest of their urban counterparts (4.00, [2.00, 7.25]; urban vs. DP+ , p = .017). Similarly, rural children exhibited reduced mRNA expression of immune markers, both at baseline and following lipopolysaccharide (LPS) stimulation. Whereas LPS stimulation induced increased secretion of Th1 and proinflammatory cytokines in rural DP+ children compared to rural DP- children and urban children. Bronchoalveolar lavage of mice with intranasal instillation of dust extracts from DP household showed a significant decrease in eosinophils as compared to those of control mice (p < .05). Furthermore, DP dust strongly inhibited gene expression of Th2 signature cytokines and induced IL-17 expression in the murine asthma model. CONCLUSIONS: Immune responses of rural children were dampened compared to urban children and those exposed to DP had further downregulated immune responsiveness. DP dust extracts ameliorated Th2-driven allergic airway inflammation in mice. Determining active protective components in the rural environment may provide directions for the development of primary prevention of asthma.
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Asma , Hipersensibilidad , Niño , Humanos , Animales , Ratones , Lipopolisacáridos/efectos adversos , Alérgenos , Citocinas/metabolismo , Polvo , Inflamación , Modelos Animales de Enfermedad , Inmunidad , Ratones Endogámicos BALB C , Ovalbúmina/efectos adversosRESUMEN
The emissions and exposure limits for airborne PM0.1 are lacking, with limited scientific data for toxicity. Therefore, we continuously monitored and calculated the number and mass concentrations of airborne PM0.1 in December 2017, January 2018 and March 2018 during the high pollution period in Guangzhou. We collected PM0.1 from the same period and analyzed their chemical components. A549, THP-1 and A549/THP-1 co-cultured cells were selected for exposure to PM0.1, and evaluated for toxicological responses. Our aims are to 1) measure and analyze the number and mass concentrations, and chemical components of PM0.1; 2) evaluate and compare PM0.1 toxicity to different airway cells models at different time points. Guangzhou had the highest mass concentration of PM0.1 in December 2017, while the number concentration was the lowest. Chemical components in PM0.1 vary significantly at different time periods, and the correlation between the chemical composition or source of PM0.1 and the mass and number concentration of PM0.1 was dissimilar. Exposure to PM0.1 disrupted cell membranes, impaired mitochondrial function, promoted the expression of inflammatory mediators, and interfered with DNA replication in the cell cycle. The damage caused by exposure to PM0.1 at different times exhibited variations across different types of cells. PM0.1 in March 2018 stimulated co-cultured cells to secrete more inflammatory mediators, and CMA was significantly related to the expression of them. Our study indicates that it is essential to monitor both the mass and number concentrations of PM0.1 throughout all seasons annually, as conventional toxicological experiments and the internal components of PM0.1 may not effectively reveal the health damages caused by elevated number levels of PM0.1.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Material Particulado/toxicidad , Material Particulado/análisis , China , Mediadores de Inflamación , Tamaño de la Partícula , Monitoreo del AmbienteRESUMEN
Recent research indicates that exposure to pollen increases the risk and severity of respiratory infections, while studies also suggest that it may possess a protective function. Our aim was to investigate how exposure to common pollen modifies airway cells' responses to viral- or bacterial-like challenges and vice versa. Cocultured A549 and THP-1 cells were exposed to three doses of four different pollens (Alnus glutinosa, Betula pendula, Phleum pratense, or Ambrosia artemisiifolia) and subsequently to Toll-like receptor (TLR) ligands mimicking bacterial and viral challenges (TLR3, TLR4, TLR7/8). The stimulation experiment was replicated in reverse order. Toxicological and immunological end points were analyzed. When cells were primed with pollen, especially with grass (P. pratense) or weed (A. artemisiifolia), the ability of cells to secrete cytokines in response to bacterial- and viral-like exposure was decreased. In contrast, cells primed with viral ligand TLR7/8 showed greater cytokine responses against pollen than cells exposed to ligands or pollen alone. Our results suggest that pollen exposure potentially weakens immune reactions to bacterial- or viral-like challenges by modulating cytokine production. They also indicate that TLR7/8-mediated viral challenges could elicit exaggerated immune responses against pollen. Both mechanisms could contribute to the acceleration and complication of infections during the pollen season.
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Polen , Receptor Toll-Like 7 , Técnicas de Cocultivo , Citocinas , Inmunidad , AlérgenosRESUMEN
Epidemiological studies have revealed some alterations in systemic immunity that associate with farm exposure and the risk of respiratory diseases, but in vitro studies focusing on immunological responses in the airways are scarce. Our aim was to assess how cowshed dust affects the integrity and inflammation of human airway tissue in vitro. Cowshed dust samples were collected from four different dairy farms. Lung tissue constructs were exposed to dust samples in air-liquid interface. Transepithelial resistance of the tissue, secreted proteins, and a panel of pro-inflammatory cytokines, growth factors, and chemokines were analysed. Cowshed dust stimulation was associated mainly with increased production of IL-13, IL-15, IP-10 and IFN-γ. Some differences between farms were seen. Only one farm dust sample induced a significant change in transepithelial resistance, whereas dust from two of the farms induced the secretion of proteins. The exposure to cowshed dust affected protein and cytokine secretion, but the response profiles were not uniform between farms. The effect on tight junction dynamics was less pronounced, suggesting the relevance of soluble factors in induced responses in the airways. Our results indicate that in addition to farm type, the contribution of cowshed characteristics to dust composition and its immunomodulatory properties should be taken into account.
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Citocinas , Polvo , Humanos , Bovinos , Animales , Polvo/análisis , Granjas , Citocinas/metabolismo , Pulmón/metabolismo , InflamaciónRESUMEN
The sources, sizes, components, and toxicological responses of particulate matter (PM) have demonstrated remarkable spatiotemporal variability. However, associations between components, sources, and toxicological effects in different-sized PM remain unclear. The purposes of this study were to 1) determine the sources of PM chemical components, 2) investigate the associations between components and toxicology of PM from Guangzhou high air pollution season. We collected size-segregated PM samples (PM10-2.5, PM2.5-1, PM1-0.2, PM0.2) from December 2017 to March 2018 in Guangzhou. PM sources and components were analyzed. RAW264.7 mouse macrophages were treated with PM samples for 24 h followed by measurements of toxicological responses. The concentrations of PM10-2.5 and PM1-0.2 were relatively high in all samples. Water-soluble ions and PAHs were more abundant in smaller-diameter PM, while metallic elements were more enriched in larger-diameter PM. Traffic exhaust, soil dust, and biomass burning/petrochemical were the most important sources of PAHs, metals and ions, respectively. The main contributions to PM were soil dust, coal combustion, and biomass burning/petrochemical. Exposure to PM10-2.5 induced the most significant reduction of cell mitochondrial activity, oxidative stress and inflammatory response, whereas DNA damage, an increase of Sub G1/G0 population, and impaired cell membrane integrity were most evident with PM1-0.2 exposure. There were moderate or strong correlations between most single chemicals and almost all toxicological endpoints as well as between various toxicological outcomes. Our findings highlight those various size-segregated PM-induced toxicological effects in cells, and identify chemical components and sources of PM that play the key role in adverse intracellular responses. Although fine and ultrafine PM have attracted much attention, the inflammatory damage caused by coarse PM cannot be ignored.
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Contaminantes Atmosféricos , Contaminación del Aire , Material Particulado , Animales , Ratones , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China , Polvo/análisis , Monitoreo del Ambiente , Tamaño de la Partícula , Material Particulado/toxicidad , Material Particulado/análisis , Estaciones del AñoRESUMEN
In recent years, evidence of the synergistic effects of pollen and viruses on respiratory health has begun to accumulate. Pollen exposure is a known risk factor for the incidence and severity of respiratory viral infections. However, recent evidence suggests that pollen exposure may also inhibit or weaken viral infections. A comprehensive summary has not been made and a consensus on the synergistic health effects has not been reached. It is highly possible that climate change will increase the significance of pollen exposure as a cause of respiratory problems and, at the same time, affect the risk of infectious disease outbreaks. It is important to accurately assess how these two factors affect human health separately and concurrently. In this review article, for the first time, the data from previous studies are combined and reviewed and potential research gaps concerning the synergistic effects of pollen and viral exposure are identified.
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Virosis , Virus , Humanos , Cambio Climático , Polen , Factores de Riesgo , Virosis/epidemiología , AlérgenosRESUMEN
Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force. Such partial coating is difficult to self-repair to achieve full coating due to the limited membrane fluidity. Building on our understanding of the detailed coating process, we develop a general approach for fixing the partial CM coating: external phospholipid is introduced as a helper to increase CM fluidity, promoting the final fusion of lipid patches. The NPs coated with this approach have a high ratio of full coating (~23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of ~6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.
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Nanopartículas , Neoplasias , Humanos , Membrana Celular/metabolismo , Adsorción , Fosfolípidos/metabolismo , Neoplasias/terapia , Neoplasias/metabolismoRESUMEN
Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.
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Microbioma Gastrointestinal , Hipersensibilidad , Animales , Bacterias/genética , Polvo , Endotoxinas , Hipersensibilidad/microbiología , Hipersensibilidad/prevención & control , Inmunoglobulina E , Inflamación , Ratones , OvalbúminaRESUMEN
The sources and chemical components of urban air particles exhibit seasonal variations that may affect their hazardousness to human health. Our aims were to investigate winter and spring variation in particulate matter (PM) sources, components and toxicological responses of different PM size fractions from samples collected in Guangzhou, China. Four size-segregated PM samples (PM10-2.5, PM2.5-1, PM1-0.2, and PM0.2) were collected separately during winter (December 2017 and January 2018) and spring (March 2018). All PM samples were analyzed for chemical components and characterized by source. RAW 264.7 macrophages were exposed to four doses of PM samples for 24 h. Cytotoxicity, oxidation, cell cycle, genotoxicity and inflammatory parameters were tested. PM concentrations were higher in the winter samples and caused more severe cytotoxicity and oxidative damage than to PM in the spring samples. PM in winter and spring led to increases in cell cycle and genotoxicity. The trends of size-segregated PM components were consistent in winter and spring samples. Metallic elements and PAHs were found in the largest concentrations in winter PM, but ions were found in the largest concentrations in spring PM. metallic elements, PAHs and ions in size-segregated PM samples were associated with most toxicological endpoints. Soil dust and biomass burning were the main sources of PM in winter, whereas traffic exhaust and biomass burning was the main source with of spring PM. Our results suggest that the composition of PM samples from Guangzhou differed during winter and spring, which led to strong variations in toxicological responses. The results demonstrate the importance of examining a different particle sizes, compositions and sources across different seasons, for human risk assessment.
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Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Contaminantes Atmosféricos/análisis , China , Monitoreo del Ambiente , Humanos , Tamaño de la Partícula , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , Estaciones del AñoRESUMEN
BACKGROUND: Asthma is one of the most common chronic diseases in childhood, and the prevalence has been increasing over the past few decades. One of the most consistent epidemiological findings is that children living in a farming or rural environment are protected from development of asthma and allergies, but the protective factors in rural China are not clear. METHODS: A community-based, cross-sectional epidemiological study was performed in a total of 17,587 children aged 5-8 years, 3435 from Hong Kong (urban) and 14,152 from Conghua (rural county in southern China). Asthma and allergic symptoms as well as environmental exposures were ascertained by using a standardized and validated questionnaire. RESULTS: The prevalence of current wheeze was significantly lower in rural Conghua than that of urban Hong Kong (1.7% vs. 7.7%, p < 0.001). A lower rate of asthma ever was also reported in rural children compared with their urban counterparts (2.5% vs. 5.3%, p < 0.001). After adjusting for confounding factors, exposure to agricultural farming (adjusted odds ratio 0.74, 95% confidence interval: 0.56-0.97) and poultry (0.75, 0.59-0.96) were the most important factors associated with the asthma-protective effect in the rural area. Further propensity score-adjusted analysis indicated that such protection conferred by living in the rural environment was mainly attributable to poultry exposure. CONCLUSIONS: We confirmed that the prevalence of asthma and atopic disorders was significantly lower in rural children when compared with their urban peers. Exposure to poultry and agricultural farming are the most important factors associated with asthma protection in the rural area.
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Asma , Aves de Corral , Animales , Asma/epidemiología , Asma/etiología , Asma/prevención & control , Niño , Conservación de los Recursos Naturales , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Prevalencia , Factores de Riesgo , Población Rural , Encuestas y CuestionariosRESUMEN
Little evidence is available regarding the impact of different sizes of inhaled particulate matter (PM) on inflammatory responses in healthy young adults in connection with toxicological responses. We conducted a five-time repeated measurement panel study on 88 healthy young college students in Guangzhou, China from December 2017 to January 2018. Blood samples were collected from each participant and tested for tumor necrosis factor alpha (TNF-α) levels every week for 5 consecutive weeks. Mass concentrations of ambient PM2.5, PM1, PM0.5 and number concentrations of ambient PM0.1 were measured. RAW 264.7 macrophages were exposed to PM (PM10-2.5, PM2.5-1, PM1-0.2, PM0.2) collected at the same time as the panel study. Cytotoxicity, oxidation and inflammatory parameters, cell cycle and genotoxicity were tested. Particles were characterized for their chemical composition. The trends of associations between PM2.5, PM1, PM0.5 and TNF-α level were consistent in lag 0 and 3 days, and the relative risk decreased as the particle size decreased. All the ambient air pollutants had the similar change trends in lag 1, 4 and 5 days. Similar results in RAW 264.7 macrophages were found; PM10-2.5 induced the greatest TNF-α and macrophage inflammatory protein 2 (MIP-2) productions and oxidative damage. PM1-0.2 and PM0.2 induced more significant dose-dependent increases of cell cycle and genotoxic response. In the component concentrations of PM samples, metal elements were PM10-2.5 > PM2.5-1 > PM0.2 ≥ PM1-0.2; ions and polycyclic aromatic hydrocarbons (PAHs) were PM0.2 > PM1-0.2 > PM2.5-1 > PM10-2.5. Our results suggested that exposure to all particle sizes was significantly associated with inflammation among healthy young adults and toxicological responses in RAW 264.7 macrophages. Different human and toxicological reactions caused by PM samples indicated the importance of investigating various particle sizes.
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Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Humanos , Inflamación/inducido químicamente , Tamaño de la Partícula , Material Particulado/análisis , Factor de Necrosis Tumoral alfa , Adulto JovenRESUMEN
Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13-3.16; P = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40; P = 0.258, P = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30; P = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
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Asma , Cromosomas Humanos Par 17 , Lipopolisacáridos , Alelos , Animales , Asma/genética , Bovinos , Citocinas/genética , Femenino , Humanos , Inmunidad Innata , Leucocitos Mononucleares , Ratones , Ruidos Respiratorios/genéticaRESUMEN
BACKGROUND: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen-activated protein kinase (MAPK) pathway with its negative regulator dual-specificity phosphatase-1 (DUSP1) is presumably associated with asthma development. OBJECTIVES: We aimed to investigate the role of MAPK signaling in childhood asthma and its environment-mediated protection, including a representative selection of 232 out of 1062 children from two cross-sectional cohorts and one birth cohort study. METHODS: Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm-dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation. RESULTS: Asthmatic children expressed significantly less DUSP1 (p = .006) with reduced acetylation at histone H4 (p = .012) compared with healthy controls. Farm-dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs; p ≤ .01). Single-cell protein analysis revealed downregulated pMAPKs upon farm-dust stimulation in B cells, NK cells, monocytes, and T-cell subpopulations. CONCLUSION: Lower DUSP1 baseline levels in asthmatic children and anti-inflammatory regulation of MAPK in several immune cell types by farm-dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti-inflammatory characteristics of farming environments.
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Asma , Leucocitos Mononucleares , Asma/epidemiología , Asma/genética , Niño , Estudios de Cohortes , Estudios Transversales , Humanos , Proteínas Quinasas Activadas por MitógenosRESUMEN
Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.
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Antineoplásicos Alquilantes/administración & dosificación , Materiales Biomiméticos/química , Membrana Celular/química , Portadores de Fármacos/química , Neoplasias/tratamiento farmacológico , Animales , Composición de Medicamentos/métodos , Endocitosis , Células HeLa , Humanos , Masculino , Ratones , Microscopía Electrónica de Transmisión , Nanopartículas/química , Nanopartículas/ultraestructura , Porosidad , Células RAW 264.7 , Propiedades de SuperficieRESUMEN
Exposure to farm environment has been shown to both protect from allergic diseases and increase the risk of respiratory syndromes. Mechanisms have been previously investigated by using farm dust extracts or specific components of dust. The use of authentic farm dust would better reflect the natural exposure. The aim of our study was to highlight the importance of proper assessment of the cow stable dust characteristics before conducting further investigations. For this purpose, we characterized microbiome and size distribution of unprocessed cow stable dust and its toxicological properties, as they have been often overlooked in search of protective factors. Stable dust samples from four Finnish dairy farms were collected by utilizing two different collection methods. Toxicological potential was analysed by stimulating co-cultures of lung epithelial and macrophage-like cells with dust. Size and mass distributions of airborne particles in the stables and bacterial and fungal microbiota of the dust were analysed. Stimulation with dust did not affect viability, but heightened oxidative stress responses and cytokine secretion, and slightly reduced the metabolic activity. There were a few differences in responses between farms, however, the differences were mainly in the intensity and not in the direction of the response. Cellular responses induced by dusts collected by different sampling methods did not differ substantially. Unprocessed stable dust samples showed relatively low direct toxicity but were able to trigger immune responses in studied cell model. This suggest that these dust collection methods could be utilized when investigating e.g. asthma-protective mechanisms.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Polvo/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire Interior/efectos adversos , Animales , Bacterias/aislamiento & purificación , Bovinos , Supervivencia Celular , Células Cultivadas , Técnicas de Cocultivo , Industria Lechera , Células Epiteliales/metabolismo , Hongos/aislamiento & purificación , Vivienda para Animales , Humanos , Interleucina-6/metabolismo , Macrófagos/metabolismo , Microbiota , Estrés Oxidativo , Tamaño de la Partícula , Alveolos Pulmonares/citología , Especies Reactivas de Oxígeno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background Although several studies have focused on the associations between particle size and constituents and blood pressure, results have been inconsistent. Methods and Results We conducted a panel study, between December 2017 and January 2018, in 88 healthy university students in Guangzhou, China. Weekly systolic blood pressure and diastolic blood pressure were measured for each participant for 5 consecutive weeks, resulting in a total of 440 visits. Mass concentrations of particles with an aerodynamic diameter of ≤2.5 µm (PM2.5), ≤1.0 µm (PM1.0), ≤0.5 µm (PM0.5), ≤0.2 µm (PM0.2), and number concentrations of airborne particulates of diameter ≤0.1 µm were measured. Linear mixed-effect models were used to estimate the associations between blood pressure and particles and PM2.5 constituents 0 to 48 hours before blood pressure measurement. PM of all the fractions in the 0.2- to 2.5-µm range were positively associated with systolic blood pressure in the first 24 hours, with the percent changes of effect estimates ranging from 3.5% to 8.8% for an interquartile range increment of PM. PM0.2 was also positively associated with diastolic blood pressure, with an increase of 5.9% (95% CI, 1.0%-11.0%) for an interquartile range increment (5.8 µg/m3) at lag 0 to 24 hours. For PM2.5 constituents, we found positive associations between chloride and diastolic blood pressure (1.7% [95% CI, 0.1%-3.3%]), and negative associations between vanadium and diastolic blood pressure (-1.6% [95% CI, -3.0% to -0.1%]). Conclusions Both particle size and constituent exposure are significantly associated with blood pressure in the first 24 hours following exposure in healthy Chinese adults.
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Contaminantes Atmosféricos/análisis , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/análisis , Adulto , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , China/epidemiología , Femenino , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Masculino , Morbilidad/tendencias , Tamaño de la Partícula , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire-based studies by self-report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6-year-old children. METHODS: Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. RESULTS: Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35-7.07) and 3.16 (1.43-6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. CONCLUSION: These results underline the importance of prevention and remediation efforts of moisture and mold-damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development.
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Asma , Óxido Nítrico , Niño , Espiración , Hongos , Humanos , Lactante , InflamaciónRESUMEN
Evidence of the effects of various particle sizes and constituents on blood biomarkers is limited. We performed a panel study with five repeated measurements in 88 healthy college students in Guangzhou, China between December 2017 and January 2018. Mass concentrations of particles with aerodynamic diameters ≤ 2.5 µm (PM2.5), PM1, and PM0.5 and number concentrations of particles with aerodynamic diameters ≤ 200 nm (PN0.2) and PN0.1 were measured. We used linear mixed-effect models to explore the associations of size-fractionated particulate matter and PM2.5 constituents with five blood biomarkers 0-5 days prior to blood collection. We found that an interquartile range (45.9 µg/m3) increase in PM2.5 concentration was significantly associated with increments of 16.6, 3.4, 12.3, and 8.8% in C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and endothelin-1(ET-1) at a 5-day lag, respectively. Similar estimates were observed for PM1, PM0.5, PN0.2, and PN0.1. For PM2.5 constituents, consistent positive associations were observed between F- and sVCAM-1 and CRP and between NH4+ and MCP-1, and negative associations were found between Na+ and MCP-1 and ET-1, between Cl- and MCP-1, and between Mg2+ and sVCAM-1. Our results suggested that both particle size and constituent exposure are significantly associated with circulating biomarkers among healthy Chinese adults. Particularly, PN0.1 at a 5-day lag and F- and NH4+ are the most associated with these blood biomarkers.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Biomarcadores , China , Exposición a Riesgos Ambientales/análisis , Humanos , Tamaño de la Partícula , Material Particulado/análisis , Adulto JovenRESUMEN
Existing evidence is scarce concerning the various effects of different PM sizes and chemical constituents on blood lipids. A panel study that involved 88 healthy college students with five repeated measurements (440 blood samples in total) was performed. We measured mass concentrations of particulate matter with diameters ≤ 2.5 µm (PM2.5), ≤1.0 µm (PM1.0), and ≤0.5 µm (PM0.5) as well as number concentrations of particulate matter with diameters ≤ 0.2 µm (PN0.2) and ≤0.1 µm (PN0.1). We applied linear mixed-effect models to assess the associations between short-term exposure to different PM size fractions and PM2.5 constituents and seven lipid metrics. We found significant associations of greater concentrations of PM in different size fractions within 5 days before blood collection with lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A (ApoA1) levels, higher apolipoprotein B (ApoB) levels, and lower ApoA1/ApoB ratios. Among the PM2.5 constituents, we observed that higher concentrations of tin and lead were significantly associated with decreased HDL-C levels, and higher concentrations of nickel were associated with higher HDL-C levels. Our results suggest that short-term exposure to PM in different sizes was deleteriously associated with blood lipids. Some constituents, especially metals, might be the major contributors to the detrimental effects.