RESUMEN
PURPOSE: The aim of this study is to clarify the changes of peripheral CD3-CD56+CD16+ NK cells and their correlation with Th1/Th2 immunity profiles in asthma during the phase of acute upper respiratory viral infections (AURVIs). METHODS: Peripheral venous blood and induced sputum samples were collected from 56 mild asthma patients, 49 asthma patients with AURVIs and 50 healthy subjects. Peripheral CD3-CD56+CD16+ NK cells were monitored by flow cytometry during the course of acute viral infections. Meanwhile, the induced sputum Th2 cytokines IL-4 and IL-5, and Th1 cytokine IFN-γ were also detected by ELISA assay. RESULTS: The asthmatics had lower levels of peripheral CD3-CD56+CD16+ NK cells populations as well as higher induced sputum cytokines (IL-4, IL-5 and IFN-γ) compared to healthy controls at baseline. Upon upper respiratory viral infections, peripheral CD3-CD56+CD16+ NK cells numbers in asthma patients sharply elevated on day 3 and slowly decreased by day 14, in accordance with induced sputum IFN-γ changes. IL-4 and IL-5 levels spiked much later (day 8) and lasted until day 14. Compared with asthma alone group, the IFN-γ/IL-4 and IFN-γ/IL-5 ratios of the asthma patients with AURVIs on day 1 were higher and peaked on day 3. The changes of peripheral CD3-CD56+CD16+ NK cells proportions positively correlated with the IFN-γ/IL-4 and IFN-γ/IL-5 ratios on day 1 to day 3 in asthma subsequent to upper respiratory viral infections. CONCLUSIONS: Our findings showed an imbalanced Th1/Th2 immunity in airways of asthma with acute upper respiratory viral infections. Upregulated peripheral CD3-CD56+CD16+ NK cells play a crucial role in biased Th1 immunity of airways in asthma during the acute phase of viral infections. The anti-viral Th1 immunity by targeting NK cells may be a possible therapeutic option for virus-induced asthma exacerbation.
Asunto(s)
Asma , Interleucina-4 , Humanos , Regulación hacia Arriba , Interleucina-5 , Células Asesinas Naturales , Citocinas , Antígeno CD56/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Amino acids (AAs) are crucial nutrients and fundamental building blocks of organisms that can be utilized to assess nutritional status and detect diseases. However, insufficient information has been reported on plasma AA in the Eastern Chinese population. METHODS AND STUDY DESIGN: 1859 persons who underwent physical examination in our hospital from January to December 2020 were enrolled. Plasma AA levels were determined by ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS.), and the effects of age and sex on 19 plasma AA profiles were analyzed. The Python language was used for data analysis and graphic visualization. RESULTS: Plasma arginine, proline, threonine, as-paragine, phenylalanine, and glycine in males, and plasma lysine, leucine, proline, valine, isoleucine, alanine, tyrosine, phenylalanine, and hydroxyproline levels in females increased with age. The 2-aminobutyric acid and serine levels in both sexes, and isoleucine, valine, leucine, and histidine levels in males decreased with age. Glycine level was higher in females than in males, and other 17 AAs except arginine and aspartate were higher in males than in females. CONCLUSIONS: Our study indicated that plasma AA levels can reflect the nutritional status and dietary structure of the population, with high obesity rate and high incidence of chronic diseases in eastern China. Age has certain effects on plasma AA levels, especially compared with sex.
Asunto(s)
Aminoácidos , Isoleucina , Femenino , Masculino , Humanos , Leucina , Cromatografía Liquida , Espectrometría de Masas en Tándem , Prolina , Glicina , Fenilalanina , Valina , ArgininaRESUMEN
OBJECTIVE: To study the relationship between fasting plasma amino acids and obesity in the physical examination population. METHODS: A total of 1859 persons who underwent physical examination in the Second Affiliated Hospital Zhejiang University School of Medicine from January to December 2020 were enrolled. Fasting plasma amino acids concentrations and body fat ratio(BFR) were respectively determined by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) and Inbody instrument. According to body mass index and gender grouping, Python language was used for data analysis and graphic visualization to explore the relationship between body mass index, gender and plasma amino acids levels. RESULTS: The plasma levels of glycine, serine and asparagine in the overweight and obesity groups were significantly lower than those in the normal group, especially the levels in the obesity group were lower than those in the overweight group in males(P<0.05). There was no significant difference in plasma levels of lysine, tryptophan, arginine and hydroxyproline among normal, overweight and obesity groups(P>0.05). The plasma levels of leucine, valine, tyrosine, phenylalanine(in males), isoleucine(in females) and alanine in the overweight and obesity groups were significantly higher than those in the normal group, and the levels in the obesity group were higher than those in the overweight group except alanine(P<0.05). BFR was positively correlated with body mass index. BFR in females increased significantly with age after 50 years old(P<0.05). CONCLUTION: The rate of overweight and obesity among the health screening population is high.
Asunto(s)
Metionina , Sobrepeso , Masculino , Femenino , Humanos , Persona de Mediana Edad , Cromatografía Liquida , Espectrometría de Masas en Tándem , Aminoácidos , Alanina , Leucina , ObesidadRESUMEN
BACKGROUND: House dust mite (HDM) inhalation can cause airway epithelial damage which is implicated in the process of airway inflammation in asthma. High mobility group box 1 (HMGB1) is critically required for cellular damage and apoptosis as an important endogenous danger signal. Recently, Clara cell 16KDa protein (CC16) has been identified to exert anti-inflammatory and immunomodulatory influence in various injury-related diseases model. However, little is known about its ability to protect against airway epithelial injury in allergic asthma. This study was aimed to clarify the protective roles of CC16 on airway epithelia in HDM-induced asthma and the regulation of HMGB1 by CC16. METHODS: Mice were sensitized and challenged by HDM extract and administrated intranasally with CC16 (5 µg/g or 10 µg/g) or saline in the challenged period. The BEAS-2B human airway epithelial cell line were cultured with CC16 or the control vehicle and then exposed to HDM. Knockdown or overexpression of HMGB1 was induced by cell transfection or intratracheal injection of recombinant adenovirus. RESULTS: CC16 treatment decreased airway inflammation and histological damage of airway epithelium dose-dependently in HDM-induced asthma model. Airway epithelia apoptosis upon HDM stimulation was noticeably abrogated by CC16 in vivo and in vitro. In addition, upregulation of HMGB1 expression and its related signaling were also detected under HDM conditions, while silencing HMGB1 significantly inhibited the apoptosis of BEAS-2B cells. Furthermore, the activity of HMGB1-mediated signaling was restrained after CC16 treatment whereas HMGB1 overexpression abolished the protective effect of CC16 on HDM-induced airway epithelia apoptosis. CONCLUSIONS: Our data confirm that CC16 attenuates HDM-mediated airway inflammation and damage via suppressing airway epithelial cell apoptosis in a HMGB1-dependent manner, suggesting the role of CC16 as a potential protective option for HDM-induced asthma.
Asunto(s)
Asma/tratamiento farmacológico , Proteína HMGB1/genética , Pyroglyphidae/inmunología , Uteroglobina/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Asma/inducido químicamente , Asma/genética , Línea Celular , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Uteroglobina/farmacologíaRESUMEN
BACKGROUND: Many equations to estimate the resting energy expenditure (REE) of patients with burns are currently available, but which of them provides the best guide to optimize nutrition support is controversial. This review examined the bias and precision of commonly used equations in patients with severe burns. METHODS: A systematic search of the PubMed, Web of Science, Embase, and Cochrane Library databases was undertaken on June 1, 2023, to identify studies comparing predicted REE (using equations) with measured REE (by indirect calorimetry [IC]) in adults with severe burns. Meta-analyses of bias and calculations of precisions were performed in each predictive equation, respectively. RESULTS: Nine eligible studies and 12 eligible equations were included. Among the equations, the Toronto equation had the lowest bias (26.1 kcal/day; 95% CI, -417.0 to 469.2), followed by the Harris-Benedict equation × 1.5 (1.5HB) and the Milner equation. The Ireton-Jones equation (303.4 kcal/day; 95% CI, 224.5-382.3) acceptably overestimated the REE. The accuracy of all of the equations was <50%. The Ireton-Jones equation had the relatively highest precision (41.2%), followed by the 1.5HB equation (37.0%) and the Toronto equation (34.7%). CONCLUSION: For adult patients with severe burns, all of the commonly used equations for the prediction of REE are inaccurate. It is recommended to use IC for accurate REE measurements and to use the Toronto equation, 1.5HB equation, or Ireton-Jones equation as a reference when IC is not available. Further studies are needed to propose more accurate REE predictive models.
Asunto(s)
Metabolismo Basal , Quemaduras , Adulto , Humanos , Quemaduras/metabolismo , Calorimetría Indirecta , Metabolismo Energético , Apoyo Nutricional , DescansoRESUMEN
Anthropogenic emissions have emerged as an important source of urban atmospheric PM2.5, exacerbating air pollution and the associated health implications. This study analyses PM2.5, originating from major anthropogenic sources (industries, motor vehicles, and solid-fuel combustion for domestic applications) in the Guanzhong Plain in China, along with the parent- (p-), alkylated- (a-), and oxygenated- (o-) polycyclic aromatic hydrocarbons (PAHs) and reactive oxygen species (ROS) levels in PM2.5. Industrial emissions are mainly characterised by high abundances of benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), and benz[a]fluoranthene (BaF). The 4-ring p-PAHs, such as fluoranthene (FLA), pyrene (PYR), benzo[a]anthracene (BaA), and chrysene (CHR) proportions and the diagnostic ratios of indeno[1,2,3-cd]pyrene (IcdP)/[IcdP + benzo[ghi]perylene (BghiP)] and 1-acenaphthenone (1ACO)/[1ACO + 9-fluorenone (9FO)] in motor vehicle emission PM2.5 were higher than the other sources. Household solid fuel combustion features high proportions of methylnaphthalene (M-NAP), i.e., 2 M-NAP and 1 M-NAP and 3-ring p-PAHs. Acenaphthylene (ACY), acenaphthene (ACE), anthracene (ANT), 1,4-chrysenequinone (1,4CHRQ), and reactive oxygen species (ROS) were positively correlated among the three anthropogenic sources. Moreover, the correlations between other PAHs and ROS varied significantly among the three sources. As mixed and compound organic pollutants, 2- and 3-ring p-PAHs were more positively correlated with the ROS activity of household solid fuel combustion sources compared with industrial and motor vehicle sources. Based on the relative contribution of these three sources to PAHs in PM2.5, we estimated the cancer risks of males and females in the Guanzhong area to be 2.95 × 10-6 and 2.87 × 10-6, respectively, exceeding the safety threshold of 1 × 10-6. This study provides a basic dataset for conducting a refined source apportionment of PM2.5 and a scientific basis for further understanding the relationship between PM2.5, PAHs, and ROS in northern China.
RESUMEN
Oxidative stress is a major mediator in the pathogenesis of allergens-induced asthma. Mitochondria damage and dysfunction is considered to be closely related with oxidative stress. Apelin-13 is a novel multifunctional protein with anti-inflammatory and anti-oxidative properties in neuroinflammation and ischemia-reperfusion injury. However, its role in mitochondria homeostasis under asthma-associated airway oxidative injury and the potential mechanisms have not been elucidated. A murine model of asthma was established by house dust mite (HDM) allergen sensitization and challenge. The mice were received Apelin-13 protein through intraperitoneal administration before HDM challenge. Airway inflammation, histopathological changes and oxidative stress were examined. The regulatory effects of Apelin-13 on mitochondria function were evaluated using airway epithelial BEAS-2B cells, including mitochondria membrane potential (MMP), mitophagy and the possible signaling pathway. The HDM-challenged mice group exhibited robust inflammation and apoptosis in airway epithelium compared to the control group. The airway impairment in asthmatic mice was partly lessened after Apelin-13 administration. Meanwhile, protein expressions of mitophagy-related markers PINK1, Parkin, Tomm20 and LC3 were significantly increased in the lungs of Apelin-13-treated asthmatic mice. In vitro, Apelin-13 treatment significantly improved MMP levels and reduced ROS production in BEAS-2B cells exposed to HDM, accompanied with the increase of cell viability. Furthermore, Apelin-13 was found to promote the activation of PINK1/Parkin signaling in BEAS-2B cells, thereby increasing mitophagy activity and facilitating mitochondria homeostasis. These results demonstrate that Apelin-13 acts as a regulator of mitochondria homeostasis by driving mitophagy to protect against HDM allergen-induced airway oxidative injury. Apelin-13 may serve as a promising protective agent for treating asthma.
Asunto(s)
Asma , Mitofagia , Animales , Ratones , Mitocondrias , Homeostasis , Proteínas QuinasasRESUMEN
Glutathione (GSH) is the most abundant low-molecular-weight biological thiol in vivo and has been linked to several diseases. The accurate quantification of GSH is therefore crucial for disease diagnosis and monitoring. In this study, we prepared self-assembled Cu(I)-Cys (cysteine) nanozymes through a two-step procedure. The Cu(I)-Cys nanoparticles exhibited peroxidase-mimicking activity. Upon the addition of H2O2, they were able to oxidize 3,3,5,5-tetramethylbenzidine (TMB) into oxTMB, resulting in a measurable increase in UV-Vis absorption at 655 nm. However, in the presence of GSH, oxTMB was reduced back to TMB, leading to a decrease in UV-Vis absorption at 655 nm. By utilizing these changes in the absorption intensity, we achieved the sensitive detection of GSH with a detection limit of 2.13 µM. Moreover, taking advantage of the different peroxidase-mimicking activities of Cu(I)-Cys nanoparticles at various pH values, a sensor array with Cu(I)-Cys nanoparticles at pH 4 and pH 5 was constructed. The discrimination of GSH among Cys and ascorbic acid was achieved and the practicability of the sensor array in human serum was validated. This novel approach holds significant promise for the precise discrimination and quantification of GSH and its potential applications in disease diagnosis and therapeutics.
Asunto(s)
Glutatión , Peróxido de Hidrógeno , Humanos , Ácido Ascórbico , Cisteína , PeroxidasasRESUMEN
BACKGROUND: Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes, but we pay less attention to these people. Athymic nude mice are a murine strain with a spontaneous deficiency of the Foxn1 gene, which can result in thymic degeneration or its absence, leading to immunosuppression and a decrease in the number of T cells, and are widely used in preclinical evaluations of disease in immunocompromised populations. METHODS: We investigated the protection of the coronavirus disease 2019 (COVID-19) inactivated vaccine (CoronaVac) against the infection of wild-type SARS-CoV-2 (WH-09) or Omicron variant utilizing a hybrid-type nude-hACE2 mouse model. RESULTS: Compared with nude-hACE2/W mice, the viral load in the brain and lung tissue of nude-hACE2 mice (nude-hACE2/WV) infected with WH-09 after vaccination significantly decreased, and the histopathological changes were also reduced. The viral load in the brain and lung tissue of nude-hACE2 mice (nude-hACE2/OV) infected with the Omicron variant after vaccination was lower than that in nude-hACE2/O, but histopathological symptoms did not improve significantly. CONCLUSION: CoronaVac provides some protection against infection of both WH-09 and the Omicron variant in the nude-hACE2 mice. Our findings aimed to provide a reference for vaccination against SARS-CoV-2 in immunocompromised populations.
Asunto(s)
COVID-19 , Animales , Ratones , COVID-19/prevención & control , Ratones Desnudos , SARS-CoV-2RESUMEN
Heavy use of solid fuels in rural households of northern China emits huge amounts of fine particulate matter (i.e., PM2.5) that pose notable indoor air pollution and severe inhalation health risks. In this study, the environmental and health benefits of clean energy substitution were accessed by monitoring indoor and personal exposure to polycyclic aromatic hydrocarbons (PAHs) and their derivatives, and pulmonary function and biological parameters. After substitutions of traditional lump coal and biomass fuels by clean coal, indoor concentrations of parent PAHs (p-PAHs), alkylated PAHs (a-PAHs), oxygenated PAHs (o-PAHs), and nitro PAHs (n-PAHs) reduced by 71 %, 32 %, 70 %, and 76 %, while personal exposure concentrations decreased by 82 %, 87 %, 93 %, and 86 %, respectively. However, the proportion of low molecular weight PAHs increases, especially for 2-ring a-PAHs and 3-ring n-PAHs. Domestic solid fuel burning induces greater damage to the small airway than the large airway. Pulmonary function parameter reductions in the clean coal group are much less than those in the other two fuel groups. Salivary interleukin-6 (IL-6) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) significantly correlated with PAH species, among which p-PAHs and PAHs derivatives strongly with IL-6 and 8-OHdG, respectively. The correlation between PAHs and biomarkers in urine is insignificant. In addition, the use of clean coal can reduce the cancer risk for the four classes of PAHs by 60 %-97 %, mainly owing to the lower contributions from p-PAHs and o-PAHs. The result of the study provides scientific support for clean energy retrofit and an understanding of health benefits from solid fuel substitutions.
Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Hidrocarburos Policíclicos Aromáticos , Humanos , Contaminantes Atmosféricos/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Interleucina-6 , Monitoreo del Ambiente , Material Particulado/análisis , Contaminación del Aire Interior/análisis , Carbón Mineral/análisis , 8-Hidroxi-2'-Desoxicoguanosina , ChinaRESUMEN
Tire and road wear microplastics (TRWMPs) are one of the main non-exhaust pollutants of motor vehicles, which cause serious environmental and health issues. Here, TRWMPs in PM2.5 samples were collected in a tunnel in urban Xi'an, northwest China, during four periods [I: 7:30-10:30, II: 11:00-14:00, III: 16:30-19:30, IV: 20:00-23:00 local standard time (LST)] in summer of 2019. The chemical components of rubbers, benzothiazoles, phthalates, and amines in TRWMPs were quantified, with a total concentration of 6522 ± 1455 ng m-3 (mean ± standard deviation). Phthalates were predominant in TRWMPs, accounting for 64.8% on average, followed by rubbers (33.2%) and benzothiazoles (1.19%). The diurnal variations of TRWMPs showed the highest concentration in Period III (evening rush hour) and the lowest concentration in Period I (morning rush hour), which were not exactly consistent with the variation of the number of light-duty vehicles passed through the tunnel. The result implied that the number of vehicles might not be the most important contributor to TRWMPs concentration, whereas meteorological variables (i.e., precipitation, and relative humidity), vehicle speed, vehicle class, and road cleaning also affected their abundances. The non-carcinogenic risk of TRWMPs in this study was within the international safety threshold, but their carcinogenic risk exceeded the threshold by 2.7-4.6 times, mostly dominated by bis(2-ethylhexyl)phthalate (DEHP). This study provides a new basis for the source apportionment of urban PM2.5 in China. The high concentrations and high potential cancer risks of TRWMPs represent the requirement for more efficient measures to control light-duty vehicle emissions.
Asunto(s)
Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Microplásticos , Plásticos , Monitoreo del Ambiente , Emisiones de Vehículos/análisis , China , Vehículos a Motor , BenzotiazolesRESUMEN
OBJECTIVE: This study aimed to investigate improvements in inflammatory mediator levels in induced sputum and airway hyperresponsiveness (AHR) in cough variant asthma (CVA) during long-term inhaled corticosteroid (ICS) treatment. PATIENTS AND METHODS: Patients with CVA (N = 35) and classic asthma (N = 26) and healthy subjects (N = 24) were recruited into this study. All patients were treated with budesonide (400 µg/day). Measurement of inflammatory mediators in induced sputum and PD20-FEV(1) (the accumulated provocative dose resulting in a 20% decrease in FEV(1)) in histamine-challenged subjects was performed every three months after the start of medication. Interleukin- (IL-) 5 and IL-10 were assayed by ELISA, and the percentage of eosinophils was detected with Giemsa stain. Trends during the follow-up period were analyzed using a general linear model. RESULTS: Inflammatory mediator levels in induced sputum and PD20-FEV(1) in patients with CVA and classic asthma differed from those in the control group, although no differences were found in the two asthmatic groups. PD20-FEV(1) significantly increased in CVA patients after ICS treatment for 3 months, while classic asthma patients exhibited a delayed change in AHR. After ICS treatment, levels of IL-5 and IL-10 as well as the percentage of eosinophils in the CVA group were altered at 3 months and 6 months, respectively. Accordingly, the level of inflammatory mediators in classic asthma changed more slowly. CONCLUSION: CVA has a greater improvement in airway inflammation and airway hyperresponsiveness (AHR) than classic asthma with respect to inhaled corticosteroid (ICS). Short-term ICS considerably reduces AHR although longer treatment is required for complete control of airway inflammation.
Asunto(s)
Corticoesteroides/uso terapéutico , Asma/metabolismo , Tos/metabolismo , Mediadores de Inflamación/metabolismo , Esputo/metabolismo , Administración por Inhalación , Corticoesteroides/administración & dosificación , Adulto , Asma/tratamiento farmacológico , Tos/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-10/metabolismo , Interleucina-5/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive and irreversible loss of lung function. Clinically safe and efficacious drug treatments for IPF are lacking. Pirfenidone (an anti-inflammatory, antioxidant and anti-fibrotic small-molecule drug) is considered a promising treatment for IPF. Unfortunately, several disadvantages of pirfenidone caused by traditional administration (e.g., gastrointestinal reactions, short elimination half-life) hinder its implementation. We designed pirfenidone pH-sensitive liposomes (PSLs) to target the acidic microenvironment of IPF and act directly at the disease site through pulmonary administration. Pirfenidone was encapsulated in liposomes to extend its half-life, and modified with polyethylene glycol on the surface of liposomes to improve the permeability of the mucus layer in airways. In vitro, the cytotoxicity of pirfenidone PSLs to pulmonary fibroblasts was increased significantly at 48 h compared with that using pirfenidone. In a murine and rat model of bleomycin-induced pulmonary fibrosis, pirfenidone PSLs inhibited IPF development and increased PSL accumulation in the lungs compared with that using pirfenidone solution or phosphate-buffered saline. Pirfenidone PSLs had potentially fewer side effects and stronger lung targeting. These results suggest that pirfenidone PSLs are promising preparations for IPF treatment.
RESUMEN
Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis.
Asunto(s)
Aterosclerosis , Micelas , Abietanos , Amidas , Animales , Antiinflamatorios/farmacología , Antioxidantes , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Cinamatos , Depsidos , Células Endoteliales/metabolismo , Lipopolisacáridos , Ratones , FN-kappa B/metabolismo , Polietilenglicoles/química , Polímeros , Especies Reactivas de Oxígeno/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Ácido RosmarínicoRESUMEN
The aerobic oxidation of lignin model 2-phenoxyacetophenone (2-PAP) in cooperative ionic liquid mixtures (CoILs) with 1-ethyl-3-methylimidazolium acetate ([C2C1im]OAc) and 1-benzyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BZC1im]NTf2) was investigated. Complete degradation of 2-PAP was achieved with [C2C1im]OAc/[BZC1im]NTf2 molar ratio (RIL) of 1/1 and 1/2 at 100 °C for 2 h. The conversion and product yields from CoILs were higher than those in pure ILs, indicating the cooperative effects of [C2C1im]OAc/[BZC1im]NTf2 on cleaving aryl-ether bonds. [C2C1im]OAc promoted the catalytic cleavage of aryl-ether bonds and solvation, and [BZC1im]NTf2 induced the formation of alkyl radicals and enhanced the product selectivity. Accordingly, the highest conversion of alkali lignin (79.8%) was obtained with RIL of 5/1 at 100 °C for 2 h, and phenol monomers (306 mg/g) were selectively produced. The CoILs exhibited good catalytic capacities for oxidative depolymerization of lignin, which strongly depends on the changes in intermolecular interactions and structural organization with varying RIL.
Asunto(s)
Líquidos Iónicos , Éteres , Líquidos Iónicos/química , Lignina/química , Oxidación-Reducción , Estrés OxidativoRESUMEN
The mass inoculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines to induce herd immunity is one of the most effective measures we can deploy in the fight against coronavirus disease 2019 (COVID-19). Pregnant women are prone to a higher risk of COVID-19, and maternal infection is a risk factor for a range of neurological disorders leading to abnormal behavior in adulthood. However, there are limited clinical data to support whether vaccination or infection post-immunization in pregnant women can affect the behavioral cognition of fetuses in adulthood. In this study, human angiotensin-converting enzyme 2 pregnant mice (F0 generation) were immunized with CoronaVac and then infected with SARS-CoV-2. Subsequently, we analyzed the behavioral cognition of their adult offspring (F1 generation) using the open-field test and Morris water maze test. The adult F1 generation did not exhibit any impairments in spontaneous locomotor activity or spatial reference memory.
Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Adulto , Femenino , Ratones , Embarazo , Animales , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunidad Colectiva , VacunaciónRESUMEN
The mass inoculation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine to induce herd immunity is one of the most effective measures to fight COVID-19. The vaccination of pregnant women cannot only avoid or reduce the probability of infectious diseases, but also offers the most effective and direct protection for neonates by means of passive immunization. However, there is no randomized clinical data to ascertain whether the inactivated vaccination of pregnant women or women of childbearing age can affect conception and the fetus. We found that human angiotensin-converting enzyme 2 (hACE2) mice that were vaccinated with two doses of CoronaVac (an inactivated SARS-CoV-2 vaccine) before and during pregnancy exhibited normal weight changes and reproductive performance indices; the physical development of their offspring was also normal. Following intranasal inoculation with SARS-CoV-2, pregnant mice in the immunization group all survived; reproductive performance indices and the physical development of offspring were all normal. In contrast, mice in the non-immunization group all died before delivery. Analyses showed that inoculation of CoronaVac was safe and did not exert any significant effects on pregnancy, lactation, or the growth of offspring in hACE2 mice. Vaccination effectively protected the pregnant mice against SARS-CoV-2 infection and had no adverse effects on the growth and development of the offspring, thus suggesting that inoculation with an inactivated SARS-CoV-2 vaccine may be an effective strategy to prevent infection in pregnant women.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Lactancia , Enzima Convertidora de Angiotensina 2 , Animales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Femenino , Humanos , Ratones , Ratones Transgénicos , Embarazo , SARS-CoV-2 , Vacunas de Productos InactivadosRESUMEN
PURPOSE: Airway remodeling is an important feature of chronic asthma, and yet there are few effective therapeutic strategies. Progranulin (PGRN) has been shown to have lung protective functions, but the role of PGRN in asthmatic airway remodeling is unclear. We aim to explore the protective potential of PGRN on house dust mite (HDM)-induced airway remodeling and the underlying mechanisms. METHODS: In this study, a murine model of chronic asthma was established by HDM sensitization and challenge. Recombinant PGRN was intranasally administrated to mice during the phase of HDM challenge. TGF-ß1-treated human airway epithelial BEAS-2B cells were utilized to explore the effect of PGRN on airway epithelia exposed to profibrotic conditions and molecular mechanisms. RESULTS: We found that PGRN treatment attenuated HDM-induced airway remodeling, as evidenced by the suppression of collagen accumulation, mucus overproduction and airway smooth muscle synthesis in HDM-challenged asthmatic mice lungs. Meanwhile, PGRN also reversed the increased levels of autophagy markers and autophagosomes in airway epithelia under mimic asthmatic conditions, thereby controlling the fibrotic process in vivo and in vitro. Specifically, overexpressed HMGB1 and the subsequent RAGE/MAPKs signaling activation due to HDM exposure were abrogated in PGRN-treated asthmatic mice. Furthermore, knockdown of HMGB1 expression significantly restrained the fibrosis formation in TGF-ß1-induced airway epithelia accompanied by the downregulation of autophagic activity. However, enhancement of extracellular HMGB1 levels blunted the inhibition of autophagic flux by PGRN in airway epithelia, thereby resulting in the augmentation of collagen synthesis and fibrosis. CONCLUSION: Taken together, our data revealed that PGRN protected against asthmatic airway remodeling by negatively regulating autophagy via HMGB1 suppression, which might provide new insights into the therapeutic options for HDM-induced chronic asthma.
RESUMEN
Fluorescence polarization immunoassay (FPIA) is a homogeneous and rapid analytical method that is suitable for high-throughput screening of large numbers of samples. However, FPIA typically suffers from lower sensitivity than the well-established enzyme-linked immunosorbent assay (ELISA), limiting its wide application as an analytical tool that can be run with trace levels of an analyte. Herein, a highly sensitive FPIA for detecting amantadine (AMD) in chicken is described. To achieve high sensitivity, nine chemical tracers of AMD that employ different fluoresceins, fluorescein derivatives, and haptens were synthesized and paired with four previously produced monoclonal antibodies (mAbs). The effect of the tracer structure on the sensitivity of FPIA was investigated and discussed. We found that the tracers with a linear and shorter bridge between adamantane and fluorescein generally provided higher sensitivity. After optimization, N'-(1-adamantyl) ethylenediamine (AEDA), an AMD structural analogue labeled with fluorescein isothiocyanate (FITC), achieved the lowest IC50 value (1.0 ng/ml) in the FPIA, which was comparable to that of the heterologous ELISA format that used the same mAb7G2. We also investigated the possible recognition mechanism of mAbs in terms of conformational and electronic aspects. The developed FPIA was applied to chicken to detect AMD residue, demonstrating a limit of detection (LOD) of 0.9 µg/kg with recoveries of 76.5-89.3% and coefficients of variation (CVs) below 14.5%. These results show that the proposed FPIA is an efficient, accurate, and convenient method for the rapid screening of AMD residues in chicken. PRACTICAL APPLICATION: The fluorescence polarization immunoassay (FPIA) was developed to determine and quantify amantadine (AMD) in chicken samples with high sensitivity. This homogeneous method avoids coating and washing steps and may provide high-throughput AMD screening in chicken in 10 min with high accuracy and precision. FPIA can be used as a monitoring tool and contribute significantly to the rapid detection of AMD in chicken.
Asunto(s)
Amantadina , Inmunoensayo de Polarización Fluorescente , Análisis de los Alimentos , Carne , Amantadina/análisis , Animales , Pollos , Ensayo de Inmunoadsorción Enzimática , Análisis de los Alimentos/métodos , Límite de Detección , Carne/análisisRESUMEN
BACKGROUND: To investigate the expression of neuro-oncological ventral antigen-1 (Nova1) in small-cell lung cancer (SCLC) and its value in clinical pathological diagnosis of SCLCs. METHODS: Nova1 expression in the SCLC cell line H446, lung adenocarcinoma cell line A549, squamous cell carcinoma (SCC) cell line H226 and bronchial epithelial cell line BEAS-2B were examined by RT-PCR. It's expression in paraffin specimens of 100 SCLC cases, 15 specimens of lung adenocarcinoma cases and 15 specimens of lung SCC cases, as well as adjacent normal tissue was determined by immunohistochemistry. The positive rate of Nova1 in SCLC tissue was compared with those of traditional neuroendocrine markers CD56, Syn and CgA. RESULTS: Nova1 expression in SCLC cell line H446 was significantly higher than that of bronchial epithelial cell line BEAS-2B and lung adenocarcinoma cell line A549 and SCC cell line H226. The positive rate of Nova1 in SCLC tissue was similar to that of CD56 but higher than those of Syn and CgA. Nova1 was neither expressed in the cancer tissue nor in the adjacent normal tissue of the 15 cases of SCC and the 15 cases of adenocarcinoma. In all six cases of combined SCLC, Nova1 was expressed in the SCLC component, whereas markers of SCC or adenocarcinoma were absent. CONCLUSIONS: Nova1 can be used as a novel neuroendocrine marker for pathological diagnosis of SCLC in clinical practice with high sensitivity and specificity, in addition to its role as an independent prognostic marker of overall survival and tumour recurrence, as suggested by previous studies.