Hispidulin Alleviates Mast Cell-Mediated Allergic Airway Inflammation through FcεR1 and Nrf2/HO-1 Signaling Pathway.

Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural flavone, in a mast-cell-mediated ovalbumin (OVA)-induced allergic airway inflammation model. HPD alleviated symptoms of allergic asthma and decreased the levels of immunoglobulin (Ig) E, type 2 inflammation, immune cell infiltration, and mast cell activation in the lung. Furthermore, in vivo analysis confirmed the efficacy of HPD through the evaluation of IgE-mediated allergic responses in a mast cell line. HPD treatment inhibited mast cell degranulation through inhibition of the FcεR1 signaling pathway and suppressed the expression of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-13) through suppression of the NF-κB signaling pathway. The antioxidant effects of HPD in activated mast cells were identified through modulation of antioxidant enzymes and the Nrf2/HO-1 signaling pathway. In conclusion, HPD may be a potential therapeutic candidate for allergic airway inflammation of asthma and acts by suppressing mast cell activation and oxidative stress.

Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.

Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant.

Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization.

OBJECTIVE: Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization. METHODS: The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation. RESULTS: BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, ß-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels. CONCLUSION: BKC could be a drug candidate for the treatment of allergic asthma.

Anti-Inflammatory Effects of Clematis terniflora Leaf on Lipopolysaccharide-Induced Acute Lung Injury.

For centuries, natural products are regarded as vital medicines for human survival. Clematis terniflora var. mandshurica (Rupr.) Ohwi is an ingredient of the herbal medicine, Wei Ling Xian, which has been used in Chinese medicine to alleviate pain, fever, and inflammation. In particular, C. terniflora leaves have been used to cure various inflammatory diseases, including tonsillitis, cholelithiasis, and conjunctivitis. Based on these properties, this study aimed to scientifically investigate the anti-inflammatory effect of an ethanol extract of leaves of C. terniflora (EELCT) using activated macrophages that play central roles in inflammatory response. In this study, EELCT inhibited the essential inflammatory mediators, such as nitric oxide, cyclooxygenase-2, tumor necrosis factor-α, interleukin- (IL-) 6, IL-1ß, and inducible nitric oxide synthase, by suppressing the nuclear factor-κB and mitogen-activated protein kinase activation in macrophages. Acute lung injury (ALI) is a fatal respiratory disease accompanied by serious inflammation. With high mortality rate, the disease has no effective treatments. Therefore, new therapeutic agents must be developed for ALI. We expected that EELCT can be a promising therapeutic agent for ALI by reducing inflammatory responses and evaluated its action in a lipopolysaccharide- (LPS-) induced ALI model. EELCT alleviated histological changes, immune cell infiltration, inflammatory mediator production, and protein-rich pulmonary edema during ALI. Collectively, our results may explain the traditional usage of C. terniflora in inflammatory diseases and suggest the promising potential of EELCT as therapeutic candidate for ALI.

Early-onset stroke among people with disabilities: a national database study in South Korea from 2008 to 2017.

Background: This study investigated 10-year trend in the incidence and prevalence of ischemic, hemorrhagic, and overall strokes according to the severity and type of disability between people with and without disabilities. Methods: This serial cross-sectional analysis was conducted using national health information data during a 10-year period from 2008 to 2017. Age-standardized incidence and prevalence were analyzed for each year, according to the presence, severity, and type of disability. The odds ratio (OR) of stroke was examined using multivariable logistic regression after adjusting for socio-demographic and clinical variables collected in 2017. Findings: In total, 413,398,084 people were enrolled between 2008 and 2017. In 2017, 43,552,192 people aged 19 or older were included and 5.8% was disabled. For 10 years, age-standardized incidence of ischemic and hemorrhagic stroke decreased significantly regardless of the presence of disability. However, age-standardized incidence of stroke in disabled were almost 2.5 times higher than the non-disabled in 2017. Stroke occurs 20 years earlier in people with disabilities than in those without disabilities. In 2017, people with disabilities had higher odds of stroke compared to those without disability (OR = 4.11, 95% confidence interval [CI]: 4.06-4.16), particularly among those with severe disabilities (OR = 4.75, 95% CI: 4.67-4.84). People with major internal organ impairment showed the highest incidence of stroke (OR = 5.95, 95% CI: 5.73-6.17). The main risk factors for stroke presented in this study were disability factors, chronic diseases, and advanced age. Interpretation: People with disabilities are at a greater risk of developing stroke incidence. Developing a public health policy and identifying the risk factors for stroke in people with disabilities would be beneficial. Funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. 2022R1I1A3070074).

Growing disparity in the prevalence of chronic obstructive pulmonary disease between people with and without disabilities: a Korean nationwide serial cross-sectional study.

Few studies have examined the association between disability and chronic obstructive pulmonary disease (COPD). We compared the trends in the annual COPD prevalence between people with and without disabilities, and examined the association between disability and COPD. We linked the National Health Information Database (2008-2017) with the National Disability Registration Database, which includes more than 2 million people with disabilities every year. In the 2017 dataset, people with disabilities had a higher prevalence of COPD than those without disabilities (30.6% vs. 12.5%, P < 0.001). The age-standardized prevalence rate of COPD among people without disabilities increased from 4.2 in 2008 to 10.9% in 2017 (change of 6.7%), whereas that among those with disabilities increased from 7.0 to 17.1% (change of 10.1%). In multivariate analysis, compared to people without disabilities, those with disabilities had a higher probability of having COPD (adjusted odds ratio, 1.42; 95% confidence interval 1.42-1.43). The results of subgroup analysis by disability characteristics suggested that disabilities due to failure of an organ, such as the kidney, lung, heart, or liver, and severe disabilities were particularly vulnerable to COPD. In conclusion, people with disabilities are more likely to have COPD compared to people without disabilities. Further longitudinal studies that examine cause-and-effect relationship between disability and COPD are needed to clarify this relationship and to further investigate any potential negative effects associated with the coexistence of these conditions.

Nationwide Trends in Osteoporosis in Koreans With Disabilities From 2008 to 2017.

This study examined the 10-year trends in the prevalence of osteoporosis according to disability grade and type compared with those without disabilities in South Korea. We linked national disability registration data with the National Health Insurance claims data. Age- and sex-standardized prevalence of osteoporosis were analyzed from 2008 to 2017 according to sex, disability type, and disability grade. Adjusted odds ratios for osteoporosis according to disability characteristics in the most recent years' data were also confirmed by multivariate analysis. Over the past decade, the prevalence of osteoporosis has increased in people with disabilities compared with people without disabilities, and the gap has gradually widened from 7% to 15%. By analysis of the most recent year data, both male and female individuals with disabilities had a higher risk of osteoporosis than those without disability (odds ratios [OR] 1.72, 95% confidence interval [CI] 1.70-1.73 in males; OR 1.28, 95% CI 1.27-1.28 in females); the multivariate-adjusted OR was especially prominent in disability related to respiratory disease (OR 2.07, 95% CI 1.93-2.21 in males; OR 1.74; 95% CI 1.60-1.90 in females), epilepsy (OR 2.16, 95% CI 1.78-2.61 in males; OR 1.71; 95% CI 1.53-1.91 in females), and physical disability types (OR 2.09, 95% CI 2.06-2.21 in males; OR 1.70; 95% CI 1.69-1.71 in females). In conclusion, the prevalence and risk of osteoporosis have increased in people with disabilities in Korea. In particular, the risk of osteoporosis increases significantly in people with respiratory diseases, epilepsy, and physical disability types. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Nationwide trends in the prevalence and incidence of depressive disorders and their correlates among adults with disabilities in Korea from 2006 to 2017.

BACKGROUND: Evidence suggests that people with disabilities are more likely to suffer from depression. Previous studies have focused on depressive disorders in specific disability types or age groups using small-scale cross-sectional samples. We investigated longitudinal trends in the prevalence and incidence of depressive disorders according to disability types and severity levels in the entire Korean adult population. METHODS: The age-standardised prevalence and incidence of depressive disorders were investigated using National Health Insurance claims data from 2006 to 2017. The odds of depressive disorders by type and severity were examined using logistic regression after adjusting for sociodemographic characteristics and comorbidities based on merged 2006 to 2017 data. RESULTS: Both the incidence and prevalence of depressive disorders were higher among the disabled than the non-disabled, with the prevalence gap being larger than the incidence gap. In regression analyses, adjusting for sociodemographic characteristics and comorbidities considerably reduced the odds ratios, particularly for incidence. The severity of disabilities was inversely associated with the incidence of depressive disorders. Brain injury and disabilities in major internal organs were associated with lower odds of developing depressive disorders than in non-disabled individuals. CONCLUSIONS: A significant proportion of depressive disorders in disabled individuals are caused by financial hardships or comorbidities rather than disabilities themselves. We must pay special attention to those who cannot access healthcare services due to severe disabilities and those whose depressive disorders are misdiagnosed as intellectual disabilities. More research is required to elucidate the causal mechanisms underlying depressive disorders in people with various types and severities of disabilities.

Oleanolic Acid Acetate Inhibits Mast Cell Activation in Ovalbumin-Induced Allergic Airway Inflammation.

PURPOSE: Asthma is a complex, heterogeneous chronic inflammatory airway disease with multiple phenotypes. There has been a great progress in managing asthma, but there are still unmet needs for developing uncontrolled asthma treatments. The present study aimed to determine the effectiveness of oleanolic acid acetate (OAA) from Vigna angularis against allergic airway inflammation and the underlying mechanism of action with a focus on mast cells. METHODS: To investigate the effect of OAA in allergic airway inflammation, we used the ovalbumin (OVA)-sensitized and challenged mice. To examine allergic airway inflammation associated with immune responses of mast cell activation in vitro, various types of mast cells were used. Systemic and cutaneous anaphylaxis models were used for mast cell-mediated hyper-responsiveness in vivo. RESULTS: OAA reduced OVA-induced airway inflammatory responses such as bronchospasm, increase of immune cell infiltration and serum immunoglobulin E and G1 levels. Especially, OAA decreased the mast cell infiltration, and ß-hexosaminidase release as a mast cell activation marker in the bronchoalveolar lavage fluid. OAA inhibited mast cell degranulation in mast cell line (RBL-2H3) and primary cells (rat peritoneal mast cell and mouse bone marrow-derived mast cell). Mechanistically, OAA suppressed intracellular signaling pathways including the phosphorylation of phospholipase Cγ and nuclear factor-κB, resulting from the suppression of intracellular calcium influx and pro-inflammatory cytokine expression. Further, oral administration of OAA attenuated mast cell-mediated systemic and cutaneous anaphylaxis. CONCLUSIONS: Our study showed that OAA can inhibit mast cell-mediated allergic reaction. Consequently, the application of OAA to mast cells for the allergic airway inflammation facilitate a new direction of treating allergic asthma.

Nationwide trends in the incidence of tuberculosis among people with disabilities in Korea: a nationwide serial cross-sectional study.

OBJECTIVES: Studies on the association between disabilities and tuberculosis (TB) are scarce. We aimed to assess the risk of active TB disease among people with disabilities. METHODS: We conducted a nationwide serial cross-sectional study using national registry linkage databases from 2008 to 2017. The crude and age-standardized and sex-standardized incidence rates of TB were analyzed for each year according to the presence, type, and severity of disabilities. The crude incidence rate and odds of developing TB disease were examined with a multivariable logistic regression model using data from 2017. RESULTS: The overall incidence of active TB decreased between 2008 and 2017. The age- and sex-standardized incidence rates of TB disease among people with disabilities were significantly higher than among those without disabilities throughout all observed years (p<0.001). As of 2017, the population with disabilities had a higher crude incidence rate of active TB disease than that without disabilities (119.9/100,000 vs. 48.5/100,000 person-years, p<0.001), regardless of sex, income level, and place of residence. Compared to those without disabilities, those with disabilities had higher odds of active TB (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.15 to 1.24). Individuals with mental disabilities (aOR, 1.51; 95% CI, 1.24 to1.84) had the highest odds of active TB incidence, followed by those with developmental disabilities (aOR, 1.30; 95% CI, 1.09 to 1.55). CONCLUSIONS: People with disabilities are at a greater risk of developing TB disease. Active screening and care for TB cases would be beneficial for people with disabilities.

Risks of suicide among family members of suicide victims: A nationwide sample of South Korea.

Objective: Identifying the risks of completed suicide in suicide survivors is essential for policies supporting family members of suicide victims. We aimed to determine the suicide risk of suicide survivors and identify the number of suicides per 100,000 population of suicide survivors, bereaved families of traffic accident victims, and bereaved families with non-suicide deaths. Methods: This was a nationwide population-based cohort study in South Korea. The data were taken from the Korean National Health Insurance and Korea National Statistical Office between January 2008 and December 2017. The relationship between the decedent and the bereaved family was identified using the family database of the National Health Insurance Data. Age and gender were randomly matched 1:1 among 133,386 suicide deaths and non-suicide deaths. A proportional hazard model regression analysis was conducted after confirming the cumulative hazard using Kaplan-Meier curves to obtain the hazard ratio (HR) of completed suicide in suicide survivors. Results: Using 423,331 bereaved families of suicide victims and 420,978 bereaved families of non-suicide deaths as the control group, HR of completed suicide in suicidal survivors was found to be 2.755 [95% confidence limit (CL): 2.550-2.977]. HR for wives committing suicide after husbands' suicide was 5.096 (95% CL: 3.982-6.522), which was the highest HR among all relationships with suicide decedents. The average duration from suicide death to suicide of family members was 25.4 months. Among suicide survivors, the number of suicides per 100,000 people was 586, thrice that of people in bereaved families of traffic accident victims and in bereaved families of non-suicide deaths. Conclusion: The risk of completed suicide was three times higher in suicide survivors than in bereaved families with non-suicide deaths, and it was highest in wives of suicide decedents. Thus, socio-environmental interventions for suicidal survivors must be expanded.

Predicting Ischemic Stroke in Patients with Atrial Fibrillation Using Machine Learning.

BACKGROUND: Atrial fibrillation (AF) is a well-known risk factor for stroke. Predicting the risk is important to prevent the first and secondary attacks of cerebrovascular diseases by determining early treatment. This study aimed to predict the ischemic stroke in AF patients based on the massive and complex Korean National Health Insurance (KNHIS) data through a machine learning approach. METHODS: We extracted 65-dimensional features, including demographics, health examination, and medical history information, of 754,949 patients with AF from KNHIS. Logistic regression was used to determine whether the extracted features had a statistically significant association with ischemic stroke occurrence. Then, we constructed the ischemic stroke prediction model using an attention-based deep neural network. The extracted features were used as input, and the occurrence of ischemic stroke after the diagnosis of AF was the output used to train the model. RESULTS: We found 48 features significantly associated with ischemic stroke occurrence through regression analysis (p-value < 0.001). When the proposed deep learning model was applied to 150,989 AF patients, it was confirmed that the occurrence ischemic stroke was predicted to be higher AUROC (AUROC = 0.727 ± 0.003) compared to CHA2DS2-VASc score (AUROC = 0.651 ± 0.007) and other machine learning methods. CONCLUSIONS: As part of preventive medicine, this study could help AF patients prepare for ischemic stroke prevention based on predicted stoke associated features and risk scores.

Data resource profile: the allergic disease database of the Korean National Health Insurance Service.

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients' characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients' behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https://nhiss.nhis.or.kr).

Income differences in screening, incidence, postoperative complications, and mortality of thyroid cancer in South Korea: a national population-based time trend study.

BACKGROUND: The incidence of thyroid cancer (TC) has increased rapidly over the past few decades in Korea. This study investigated whether the TC epidemic has been driven by overdiagnosis. METHODS: We calculated the TC screening rate from mid-2008 through mid-2014, and the incidence, postoperative complication, and mortality rates of TC between 2006 and 2015, using data from the Korea Community Health Survey, the National Health Insurance Database, and the cause-of-death data of Statistics Korea. Trends in age-standardized rates of all indicators were examined, along with income gaps therein. Analyses were conducted for lung cancer and stroke as negative control outcomes. RESULTS: The incidence rate of TC increased from 46.6 per 100,000 to 115.0 per 100,000 between 2006 and 2012, and then decreased to 63.5 per 100,000 in 2015. Despite these remarkable changes in incidence, mortality did not fluctuate during the same period. High income was associated with high rates of screening, incidence, and postoperative complications, while low income showed an association with a high mortality rate. Analyses using negative control outcomes showed that high income was associated with low rates of both incidence and mortality, which contrasted with the patterns of TC. The recent decreases in TC incidence and postoperative complications, which reflect societal concerns about the overdiagnosis of TC, were more pronounced in high-income individuals than in low-income individuals. CONCLUSIONS: The time trends in income gaps in screening, incidence, postoperative complications, and mortality of TC, as well as negative control outcomes, provided corroborating evidence of TC overdiagnosis in Korea.

Risk of Cardiovascular Disease and Chronic Kidney Disease According to 2017 Blood Pressure Categories in Diabetes Mellitus.

The association between blood pressure (BP) defined by the 2017 American College of Cardiology/American Heart Association Hypertension Clinical Practice Guidelines with cardiovascular disease (CVD) and chronic kidney disease in patients with diabetes mellitus remains unclear. This study used the National Health Insurance Database of Korea that has health information of 8 922 940 persons who were screened from 2009 to 2014. We determined the BP status of 490 352 diabetes mellitus: level 1 (systolic <120 mm Hg and diastolic <80 mm Hg), level 2 (systolic 120-129 mm Hg and diastolic <80 mm Hg), level 3 (systolic 130-139 mm Hg or diastolic 80-89 mm Hg), and level 4 (systolic ≥140 mm Hg or diastolic ≥90 mm Hg). Over a mean follow-up of 5 years, 6508 CVD events (1.3%), 14 318 cases of chronic kidney disease development (2.9%), 9094 cerebrovascular events (2.0%), and 1150 CVD mortalities (0.2%) occurred. Compared with people with BP levels 1, the adjusted hazard ratios for CVD in people with BP levels 2, 3, and 4 were 1.07 (95% CI, 0.98-1.16), 1.12 (95% CI, 1.04-1.20), and 1.17 (95% CI, 1.08-1.26), respectively. There were also increased risks of chronic kidney disease (1.18 [95% CI, 1.12-1.24] and 1.22 [95% CI, 1.15-1.29]), cerebrovascular disease (1.21 [95% CI, 1.14-1.29] and 1.52 [95% CI, 1.42-1.63]), and CVD mortality (1.31 [95% CI, 1.09-1.56] and 1.91 [95% CI, 1.58-2.32]) among subjects with BP levels 3 and 4 compared with those with BP level 1. These findings provide evidence supporting the 2017 American College of Cardiology/American Heart Association Hypertension Clinical Practice Guidelines for BP targets in diabetes mellitus patients.

Association of early-onset diabetes, prediabetes and early glycaemic recovery with the risk of all-cause and cardiovascular mortality.

AIMS/HYPOTHESIS: The increasing incidence of diabetes among young adults is a disease burden; however, the effects of early-onset diabetes, prediabetes and glycaemic recovery on CVD or mortality remain unclear. We aimed to investigate the association of these factors with 10 year all-cause mortality, CVD mortality and CVD incidence in Korean young adults. METHODS: This large and longitudinal cohort study included data from the Korean National Health Insurance Service-National Health Information Database; 2,502,375 young adults aged 20-39 years without diabetes mellitus and CVD at baseline were included. Glycaemic status was measured twice, first in 2002-2003 and second in 2004-2005. Changes in fasting glucose levels were evaluated according to fasting glucose status: normal fasting glucose (NFG; <5.5 mmol/l), impaired fasting glucose (IFG; 5.5-6.9 mmol/l), and diabetic fasting glucose (DFG; ≥7.0 mmol/l). Primary outcomes were all-cause and CVD mortality risk. The secondary outcome was incidence of CVD, including acute myocardial infarction and stroke. All outcomes arose from the 10 year follow-up period 1 Jan 2006 to 31 December 2015. RESULTS: Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had increased all-cause mortality (HR [95% CI] 1.60 [1.44, 1.78] and 1.13 [1.09, 1.18], respectively) and CVD incidence (1.13 [1.05, 1.23] and 1.04 [1.01, 1.07], respectively). In those with DFG at baseline, early recovery to NFG and IFG was associated with decreased all-cause mortality (0.57 [0.46, 0.70] and 0.65 [0.53, 0.81], respectively) and CVD incidence (0.70 [0.60, 0.81] and 0.78 [0.66, 0.91], respectively). Among patients with IFG at baseline, early recovery to NFG was associated with decreased CVD mortality (0.74 [0.59, 0.93]). CONCLUSIONS/INTERPRETATION: Early-onset diabetes or prediabetes increased CVD risks and all-cause mortality after the 10 year follow-up. Furthermore, recovery of hyperglycaemia could reduce the subsequent 10 year risk for CVD incidence and all-cause mortality. Graphical abstract.

Differences in diagnosis, treatment, and survival rate of acute myeloid leukemia with or without disabilities: A national cohort study in the Republic of Korea.

We analyzed the patterns of diagnosis, treatment, and prognoses of acute myeloid leukemia (AML) patients with and without disabilities. The data were collected from the National Disability Database, the Korean Central Cancer Registry, and the Korean National Health Insurance claim database. We built a cohort of 2 776 450 people with disabilities and a nondisabled cohort of 8 329 350 people who were selected at a ratio of 1:3 by matching age and sex. From this population, adult patients who were diagnosed with AML were analyzed. The number of patients with AML were 26.74 per 100 000 in people without disabilities and 20.39 per 100 000 in those with disabilities (P < .0001). The proportion of AML patients receiving chemotherapy and those of patients receiving transplants were significantly lower in the disabled population than that of nondisabled populations (71.2% vs 77.1%, P = .0031, and 17.5% vs 26.9%, P = .002). This trend was more pronounced in subgroups of communication disability and major internal organ disorder. The median survival was 10.8 months for patients with disabilities, which was significantly shorter than 17.1 months for those without a disability (P = .002). Individuals with disabilities have a low diagnosis rate of AML and undergo less active treatment, which results in inferior prognosis.

AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-ß signaling pathway.

Asthma is characterized by airway hyperresponsiveness and allergic inflammation, detrimentally affecting the patients' quality of life. The development of new drugs for the treatment of asthma is warranted to alleviate these issues. Recent studies have demonstrated that sirtuin2 (SIRT2) aggravates asthmatic inflammation by up-regulation of T-helper type 2 responses and macrophage polarization. However, effects of SIRT2 on mast cell activation remain obscure. In this study, we investigated the effects of AGK2, an inhibitor for SIRT2, on mast cell-mediated allergic airway inflammation. Pre-treatment with AGK2 inhibited degranulation of mast cells by suppressing the FcεRI signaling pathway and intracellular calcium influx. The expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4, IL-5, IL-6, and IL-8, was inhibited via regulation of transcription factors such as NF-κB and NRF2. These effects of AGK2 were verified in passive cutaneous anaphylaxis and acute lung injury animal models. AGK2 attenuated Evans blue pigmentation by inhibiting mast cell activation and lung barrier dysfunction by inhibiting inflammatory responses in these animal models. In the ovalbumin (OVA)-induced allergic airway inflammation murine model, AGK2 alleviated allergic asthma symptoms such as lung histological changes (immune cell and mast cell infiltration, collagen deposition, and α-smooth muscle actin expression) and serum immunoglobulins (Ig) levels (IgE, OVA-specific IgE, IgG1, and IgG2a). Moreover, AGK2 reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-4, IL-5, and IL-6) and inflammatory mediators (myeloperoxidase, eosinophil peroxidase, and tumor growth factor-α) in the bronchoalveolar lavage fluid and lung tissues. In addition, the anti-fibrotic effects of AGK2 were verified using lung epithelial cells and TGF-ß/Smad reporter stable cells. In conclusion, our findings suggest that SIRT2 plays a role in mast cell-mediated airway inflammatory disease. Therefore, AGK2 is a good potential candidate for treating allergic asthma and lung inflammation.

Income-related inequality in quality-adjusted life expectancy in Korea at the national and district levels.

BACKGROUND: The aim of this study was to measure differences in quality-adjusted life expectancy (QALE) by income in Korea at the national and district levels. METHODS: Mortality rates and EuroQol-5D (EQ-5D) scores were obtained from the National Health Information Database of the National Health Insurance Service and the Korea Community Health Survey, respectively. QALE and differences in QALE among income quintiles were calculated using combined 2008-2014 data for 245 districts in Korea. Correlation analyses were conducted to investigate the associations of neighborhood characteristics with QALE and income gaps therein. RESULTS: QALE showed a graded pattern of inequality according to income, and increased over time for all levels of income and in both sexes, except for low-income quintiles among women, resulting in a widened inequality in QALE among women. In all 245 districts, pro-rich inequalities in QALE were found in both men and women. Districts with higher QALE and smaller income gaps in QALE were concentrated in metropolitan areas, while districts with lower QALE and larger income gaps in QALE were found in rural areas. QALE and differences in QALE by income showed relatively close correlations with socioeconomic characteristics, but relatively weak correlations with health behaviors, except for smoking and indicators related to medical resources. CONCLUSIONS: This study provides evidence of income-based inequalities in health measured by QALE in all subnational areas in Korea. Furthermore, QALE and differences in QALE by income were closely associated with neighborhood-level socioeconomic characteristics.