Oxidative Stress and Bronchial Asthma in Children-Causes or Consequences?
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ABSTRACT:
SUBMITTER: Jesenak M
PROVIDER: S-EPMC5523023 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description: Not available
| S-EPMC3915866 | biostudies-literature
Project description:Replication stress is a complex phenomenon that has serious implications for genome stability, cell survival and human disease. Generation of aberrant replication fork structures containing single-stranded DNA activates the replication stress response, primarily mediated by the kinase ATR (ATM- and Rad3-related). Along with its downstream effectors, ATR stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability. Understanding this response may be key to diagnosing and treating human diseases caused by defective responses to replication stress.
| S-EPMC4354890 | biostudies-literature
Project description:Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.
| S-EPMC9487245 | biostudies-literature
Project description:Influence of bronchial asthma (BA) severity on physical development in children patients was evaluated in comparison with healthy population. Materials and Methods. 1042 children and adolescents (768 boys) with atopic BA were evaluated. All children underwent standard examination in a clinical setting, including anthropometry. The control group included 875 healthy children of a comparable age (423 boys). Results. The fraction of patients with the normal, lower, and increased height among the whole group of patients with BA is close to the corresponding values in the healthy population (χ2 = 3.32, p = 0.65). The fraction of BA patients with the reduced physical development is increased monotonically and significantly when the BA severity increases: healthy group, 8.2% (72/875), BA intermittent, 4.2% (6/144), BA mild persistent 9% (47/520), BA moderate persistent, 11.7% (36/308), and BA severe persistent, 24.3% (17/70) (χ2 = 45.6, p = 0,0009). Conclusion. The fraction of the children with the reduced height is increased monotonically and significantly in the groups of increasing BA severities. At the same time, the fraction of such children in groups of intermittent and mild persistent BA practically does not differ from the conditionally healthy peers.
| S-EPMC5549479 | biostudies-other
Project description:COPD and asthma exacerbations are commonly triggered by rhinovirus infection. Potentially promoting exacerbations, impaired anti-viral signaling and attenuated viral clearance have been observed in diseased bronchial epithelium. Oxidative stress is a feature of inflammation in asthma and COPD and is prominent during exacerbations. It is not known whether oxidative stress affects the anti-viral signaling capacity. Bronchial epithelial cells from asthmatic and COPD donors were infected with rhinovirus or treated with the oxidative stressor H2O2 followed by exposure to the synthetic viral replication intermediate poly(I:C). Poly(I:C) was used to ascertain a constant infection-like burden. Gene and protein levels of antioxidants as well as anti-viral responses were measured 3 and 24 h post poly(I:C) exposure. Rhinovirus infection and poly(I:C) stimulation induced protein levels of the antioxidants SOD1 and SOD2. In asthmatic bronchial epithelial cells pre-treatment with H2O2 dose-dependently decreased the antioxidant response to poly(I:C), suggesting exaggerated oxidative stress. Further, poly(I:C)-induced IFN? gene expression was reduced after pre-treatment with H2O2. This epithelial effect was associated with a reduced expression of the pattern recognition receptors RIG-I, MDA5 and TLR3 both on gene and protein level. Pre-treatment with H2O2 did not alter antioxidant responses in COPD bronchial epithelial cells and, more modestly than in asthma, reduced poly(I:C)-induced IFN? gene expression. Knockdown of TLR3 but not RIG-I/MDA5 abrogated impairment of poly(I:C)-induced IFN? gene expression by H2O2. We developed a method by which we could demonstrate that oxidative stress impairs anti-viral signaling in bronchial epithelial cells from asthmatic and COPD patients, most pronounced in asthma. The impairment apparently reflects reduced responsiveness of TLR3. These present findings shed light on molecular mechanisms potentially causing reduced interferon responses to rhinovirus infection at exacerbations in asthma and COPD. Together, our findings suggest a possible self-perpetuating vicious cycle underlying recurrent exacerbations, leading to an impaired anti-viral response, which in turn leads to viral-induced exacerbations, causing more airway inflammation.
| S-EPMC6895140 | biostudies-literature
Project description:This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.
| S-EPMC5795668 | biostudies-literature
Project description:ObjectiveThis study aims to understand the differences in intestinal flora, expression of helper T cells, allergy-related indicators, and cytokine levels between children with bronchial asthma and healthy children. The study seeks to clarify the effectiveness and safety of probiotic preparations in the treatment of bronchial asthma in children, and to provide new methods for the treatment of bronchial asthma.MethodsA total of 66 pediatric patients aged 3-6 years with bronchial asthma and 35 healthy children undergoing physical examination during the same period were enrolled, designated as the asthma group and the healthy group, respectively. The asthma group was further divided into the probiotic group and the non-probiotic group based on whether probiotics were used. The gut microbiota, serum IgE antibody levels, cytokines (IL-4, IL-5, IL-9, IL-13 levels), proportions of helper T cells (Th1, Th2), and hypersensitive C-reactive protein were measured and compared among the groups.ResultsChildren with bronchial asthma had decreased abundance and reduced diversity of intestinal flora compared to the healthy group. At the genus level, the asthma group showed increased abundance of Bacteroides and decreased abundance of Faecalibacterium and Veillonella; The probiotic group demonstrated a significantly higher improvement in the abundance of these genera before and after treatment compared to the non-probiotic group (P < 0.05). Compared to the healthy group, children with asthma had elevated levels of serum IgE, IL-4, IL-5, IL-9, and IL-13, as well as a decreased Th1/Th2 ratio, all of which showed statistical differences (P < 0.05). After treatment, all immune indicators improved. Specifically, the probiotic group exhibited a more significant decrease in serum IgE, IL-4, and IL-13 levels compared to the non-probiotic group (P < 0.05).ConclusionChildren with bronchial asthma exhibit dysbiosis of intestinal flora, characterized by an increased abundance of the Bacteroides and decreased abundance of the Faecalibacterium and Veillonella. This imbalance in intestinal flora increases the risk of allergic diseases. Probiotics can effectively improve dysbiosis of intestinal flora, contributing to the balance of immune function in children, and can be used as an adjunct therapy for the treatment of bronchial asthma.
| S-EPMC11320201 | biostudies-literature
Project description:Background: Uncontrolled asthma (BA) can be complicated by cardiac conduction disturbances and arrhythmias. It is typical mainly for adult asthmatics patients. In asthmatics children the effect of bronchoconstriction on cardiac conduction, including the supraventricular component of the ECG, is currently under discussion. The objective of the research is to analyze ECG parameters of the atrial complex and atrioventricular conduction and to assess their relationship with spirometric indicators in children with BA. Methods: Hundred three patients with BA from the age of 6–17 years were examined. The spirometric parameters were evaluated, including the Tiffeneau index (TI): FEV1/FVC (%), according to the level of which the patient groups were distinguished. Group 1 (G1): with TI more than 85%, (n = 15); Group 2 (G2): with TI from 85 to 75%, (n = 40); Group 3 (G3): with TI <75%, (n = 48). The ECG parameters that characterize supraventricular conduction, including the PQ interval (sec) and the sPQ segment (sec), were analyzed. We had calculated relative PQ (rPQ) by the formula rPQ=PQ/PQmed, where PQ is the patient's PQ, PQmed are the median PQ values of healthy children of age selected. Results: The duration of the PQ in groups G1 and G2 was 0.13 (0.11; 0.14) s; and 0.13 (0.12; 0.14) s, respectively, which is statistically significantly less than in patients of groups G3–0.14 (0.13; 0.15] s, p = 0.01. The duration of the sPQ segment in children of groups G1 and G2 was also generally shorter than in patients of groups G3, and amounted, respectively, to 0.05 (0.04; 0.06) s, 0.04 (0.04; 0.05) s, and 0.06 (0.04; 0.07) s, p = 0.02. The rPQ increased progressively as TI decreased and amounted in G1 to 92.9 (85.7; 106.3) %, in G2 100.0 (92.9; 103.0) %, and in G3 104 (100.0; 107.7) %, p = 0.009. A statistically significant negative correlation between IT and PQ–r = ?0.23, p = 0.02; with sPQ–r = ?0.20, p = 0.045; and with rPQ–r = ?0.25, p = 0.01 was revealed. Conclusion: A decrease in TI in asthmatics children is associated with a prolongation of the PQ. This may indicate a slowdown in supraventricular conduction in patients with uncontrolled asthma and, thus, be considered as a risk for the formation of subsequent supraventricular arrhythmias.
| S-EPMC7524896 | biostudies-literature
Project description:The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood-retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1?, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD.
| S-EPMC6802648 | biostudies-literature
Project description:BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
| S-EPMC9549178 | biostudies-literature