Abstract
Purpose
Broncho‐Vaxom (BV) is known to attenuate allergic airway inflammation and chronic bronchitis in humans, but the underlying mechanism of this gut‐mediated immunity remains unclear. ...This study investigated the effects of an oral BV on gut and systemic short‐chain fatty acids (SCFAs) and immune responses.
Methods
Oral BV was administered daily for 15 days prior to commencing the study in an asthma mouse model. Asthma was induced by ovalbumin (OVA) sensitization followed by a challenge with 1% OVA by inhalation. Asthmatic phenotypes, gut‐ and systemic‐ immune responses, and SCFAs in the cecum and blood were then investigated.
Results
Airway hyperresponsiveness, total immunoglobulin E production, and pulmonary inflammation were all significantly suppressed by BV. The interleukin‐13 level was also suppressed, whereas TGF‐β expression was increased, in the lungs of the BV‐treated mice. The regulatory T (Treg) cell numbers were increased in the small intestine, and the acetate level was increased in the cecum and serum after BV treatment. The levels of acetate in the cecum and serum were negatively correlated with airway hyperresponsiveness and with the eosinophil numbers in the BAL fluid of the OVA‐induced mice. There was a positive correlation between the acetate levels in the feces and serum and the lung expression of TGF‐β in the asthma mice.
Conclusions
Oral BV administration appears to prevent allergic inflammation by enhancing Treg cell proliferation and acetate production in an asthmatic mouse model.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal ...metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA.
Methods
We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry‐based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA.
Results
In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid.
Conclusion
Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. A ...polymorphism (R4810K) in the
Ring Finger Protein 213
(
RNF213
) gene, at chromosome 17q25.3, is the strongest genetic susceptibility factor for MMD in East Asian populations. MMD was regarded prevalent in childhood and in East Asian populations. However, the so-called MMD could represent only the tip of the iceberg. MMD is increasingly reported in adult patients and in Western populations. Moreover, the
RNF213
variant was recently reported to be associated with non-MMD disorders, such as intracranial atherosclerosis and systemic vasculopathy (e.g., peripheral pulmonary artery stenosis and renal artery stenosis). In this review, we summarize the spectrums of
RNF213
vasculopathy in terms of clinical and genetic phenotypes. Continuous efforts are required for pathophysiology-based diagnoses and treatment, which will benefit from collaboration between clinicians and researchers, and between stroke and vascular physicians.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Since the Global Financial Crisis of 2008-2009, the importance of non-bank financial institutions in macroprudential management has increased significantly. Consequently, major countries and ...international financial institutions have been actively discussing and implementing macroprudential supervision and regulation for non-bank financial institutions (NBFI). In this context, this paper analyzes the systemic risk of both banks and non-bank sectors (securities firms and insurance companies) in South Korea over different time periods. Using the widely recognized ΔCoVaR methodology for measuring systemic risk, the analysis reveals that systemic risk increased substantially across all three sectors (banks, securities firms, and insurance companies) during the Global Financial Crisis, the European Sovereign Debt Crisis, and the COVID-19 pandemic. Although the banking sector exhibited relatively high systemic risk compared to the securities and insurance sectors, the relative differences in systemic risk varied across the different crisis periods. Notably, during the margin call crisis in March of 2020, the gap in systemic risk between the banking and securities sectors decreased significantly compared to that during both the Global Financial Crisis and the European Sovereign Debt Crisis, indicating that securities firms had a more substantial impact on risk in the overall financial system during this period. Furthermore, I analyze the impact of the issuance of equity-linked securities (ELS) by financial institutions on systemic risk, as measured by ΔCoVaR, finding that an increase in the outstanding balance of ELS issuance by financial institutions had an impact on increasing ΔCoVaR during the three crisis periods. These findings underscore the growing importance of non-bank financial institutions in relation to South Korea's macroprudential management and supervision. To address this evolving landscape, enhanced monitoring and regulatory measures focusing on non-bank systemic risk are essential components of maintaining financial stability in the country.
Rationale
Asthma and postinfectious bronchiolitis obliterans (PIBO) are common chronic lung diseases in company with wheezing in children. However, it is not clear what is common and unique ...mechanisms between the two diseases. Thus, we used proteomic analysis to compare differences in biomarkers between children with asthma and PIBO.
Methods
Overall, 30 healthy children without respiratory underlying diseases, 18 children with asthma and 15 with PIBO were included for this study. Sequential window acquisition of all theoretical mass spectra (SWATH)‐mass spectrometry (MS) was used to measure proteins in plasma samples. To identify specific pathways of each groups, we used the ingenuity pathway analysis (IPA) software.
Results
We identified and quantified 354 proteins across all 63 samples in the SWATH‐MS analysis. Forty eight proteins were significantly different among 3 groups. The upstream analysis of IPA suggested that inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) was the upstream inhibitor of 4 differentially expressed proteins (DEPs) in asthma, while the upstream activator in PIBO subjects. Among 4 DEPs, TGF‐β1 in PIBO and periostin in asthma were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, maximal med‐expiratory flow, and PC20, respectively.
Conclusion
These findings demonstrate that transforming growth factor β1 and periostin were unique biomarkers of PIBO and asthma in children, respectively. The mechanism regulated by IKBKB may be therapeutically relevant for PIBO and asthma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Recent evidence suggests that prenatal maternal distress increases the risk of allergic diseases in offspring. However, the effect of prenatal maternal depression and anxiety on atopic ...dermatitis (AD) risk remains poorly understood. Objective We investigated whether prenatal maternal distress is associated with AD risk in offspring and whether the mechanism is mediated by reactive oxygen species. Methods Two general population-based birth cohorts formed the study. One cohort (Cohort for Childhood Origin of Asthma and Allergic Diseases COCOA) consisted of 973 mother-baby dyads, and the other (Panel Study on Korean Children PSKC) consisted of 1531 mother-baby dyads. The association between prenatal distress and AD was assessed by using Cox proportional hazards and logistic regression models. In COCOA placental 11β-hydroxysteroid dehydrogenase type 2 and glutathione levels and serum IgE levels in 1-year-old children were measured. Results In COCOA and PSKC AD occurred in 30.6% (lifetime prevalence) and 11.6% (1 year prevalence) of offspring, respectively. Prenatal maternal distress increased the risk of AD in offspring, both in COCOA (hazard ratio for depression, 1.31 95% CI, 1.02-1.69; hazard ratio for anxiety, 1.41 95% CI, 1.06-1.89) and PSKC (odds ratio for distress, 1.85 95% CI, 1.06-3.25). In COCOA both prenatal maternal depression and anxiety scores were positively related to the predicted probability of AD ( P < .001 in both). Prenatal distress decreased placental glutathione to glutathione disulfide ratios ( P = .037) and, especially in those who later had AD, decreased placental 11β-hydroxysteroid dehydrogenase type 2 levels ( P = .010) and increased IgE levels at 1 year of age ( P = .005). Conclusion Prenatal maternal depression and anxiety promote risk of AD in offspring. Maternal distress increases the predicted probability of AD. The mechanism might involve chronic stress, abnormal steroid levels, and reactive oxygen species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Allergic disease, including allergic rhinitis, asthma, and atopic dermatitis, are huge heterogeneous diseases, encompassing diverse phenotypes with different pathogenesis. Phenotype studies on ...allergic diseases are important in that they can facilitate the identification of risk factors and the underlying pathophysiologies, resulting in the application of more effective treatment, selection of better response to the treatment, and prediction of prognosis for each phenotype. In the early phase of phenotype studies in allergic diseases, artificial classifications were usually performed on the basis of clinical features, such as triggering factors or presence of atopy, which can result in the biased classification of phenotypes and be limited in the characterization of heterogeneous allergic diseases. Subsequent phenotype studies have suggested more diverse phenotypes in each allergic disease, using relatively unbiased statistical methods, such as cluster analysis or latent class analysis. The classifications of phenotypes in allergic diseases may overlap or be unstable over time due to their complex interactions with genetic and encountered environmental factors during the illness, which may affect the disease course and pathophysiologies. In this review, diverse phenotype classifications of allergic diseases, including atopic dermatitis, asthma and wheezing in children, allergic rhinitis, and atopy, have been described. The review also discusses the applications of the results obtained from phenotype studies performed in other countries to Korean children. Consideration of changes in the characteristics of each phenotype over time in individual's lifespan is needed in future research.
The occurrence of numerous cases of interstitial lung disease in children (chILD) every spring in Korea starting in 2006 raised suspicion about a causal relationship with the use of humidifier ...disinfectants (HDs). The aim of this study was to evaluate the association between HD use and the risk of chILD.
This retrospective, 1∶3 matched case-control study consisted of 16 cases of chILD that had developed between 2010 and 2011. The three groups of parallel controls (patients with acute lobar pneumonia, asthma, and healthy children) were matched by age, gender, and index date. Indoor/outdoor environmental risk factors, including HD use, were investigated by asking the guardians to complete a questionnaire.
The median age of the affected children (43.8% male) was 26 months (18.25-36.25). The chILD group did not differ significantly from the control groups with respect to socio-demographic and clinical variables. Indoor and outdoor environmental factors were not associated with a risk of chILD. However, the previous use of HDs (OR; 2.73. 95% CI; 1.41-5.90, P = 0.00) were independently associated with an increased risk.
This study showed that HDs, which are widely used in South Korea in the winter season, independently increased the risk of chILD in spring. Therefore, continuous monitoring and, if needed, changes in policy are essential to prevent and control pediatric diseases caused by toxic chemicals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exposure to environmental factors can cause interstitial lung diseases (ILDs); however, such types of ILDs are rare. From 2007 to 2011, an ILD epidemic occurred in South Korea owing to inhalational ...exposure to toxic chemicals in humidifier disinfectants (HDs). HD-associated ILDs (HD-ILDs) are characterized by rapidly progressing respiratory failure with pulmonary fibrosis and a high mortality rate of 43.8-58.0%. Although 18.1-31.1% of the general population used HDs, only a small proportion of HD users were diagnosed with HD-ILDs. This finding suggests that investigation of the pathophysiologies underlying HD-ILDs is needed in addition to the identification of susceptibility to HD-ILDs. Further, there have been several concerns regarding the diverse health effects of exposure to toxic chemicals in HDs, including those that have not been identified, and long-term prognoses in terms of pulmonary function and residual pulmonary lesions observed on follow-up chest images. In this review, we summarize the clinical features, pathologic findings, and changes in radiologic findings over time in patients with HD-ILDs and the results of previous experimental research on the mechanisms underlying the effects of toxic chemicals in HDs. Studies are currently underway to identify the pathophysiologies of HD-ILDs and possible health effects of exposure to HDs along with the development of targeted therapeutic strategies. The experience of identification of HD-ILDs has encouraged stricter control of safe chemicals in everyday life.
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