Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1β substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.
BackgroundHeart failure (HF) is one of the leading causes of morbidity and mortality in South Korea. With the rapidly aging population in the country, the prevalence of HF and its associated costs are expected to rise continuously. This study was carried out to estimate the prevalence and economic burden of HF in order to understand its impact on our society.MethodsA prevalence-based, cost-of-illness study was conducted using the 2014 Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) data. Adult HF patients were defined as those aged ≥19 years who had at least one insurance claim record with a primary or secondary diagnosis of HF (ICD-10 codes of I11.0, I13.0, I13.2, and I50.x). The costs consist of direct costs (i.e., medical and non-medical costs) and indirect costs (i.e., productivity loss cost due to morbidity and premature death). Subgroup analyses were conducted by age group, history of HF hospitalization, and type of universal health security program enrolled in.ResultsA total of 475,019 adults were identified to have HF in 2014. The estimated prevalence rate of HF was 12.4 persons per 1,000 adults. According to the base cases and the extended definition of the cases, the annual economic burden of HF from a societal perspective ranges from USD 1,414.0 to 1,560.5 for individual patients, and from USD 752.8 million to 1,085.6 million for the country. A high percentage (68.5 %) of this socioeconomic burden consist of medical costs, followed by caregiver’s cost (13.2 %), productivity loss costs due to premature death (10.8 %) and morbidity (4.2 %), and transportation costs (3.4 %). The HF patients with prior hospitalization due to HF annually spent 9.7 times more for National-Health-Insurance-covered medical costs compared to HF patients who were not previously hospitalized.ConclusionsIn the present study, HF patients who were older and had a history of prior hospitalization for HF as well as an indigent status were shown at high risk of spending more for healthcare to treat their HF. An effective disease management protocol should be employed to target this patient group.
The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).
PCRs targeting the 16S rRNA of MTC were more sensitive than those targeting 16S rDNA; 16S rRNA real-time RT-PCR showed the highest sensitivity and specificity for MTC.
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