Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Analysis of the perceptions, competencies, and educational needs for global health among Korean medical students.

PURPOSE: The purpose of this study was to examine perceptions of global health education (GHE) among medical students and their involvement in global health activities and identify priorities of educational needs for developing GHE programs. METHODS: This study was cross-sectional and conducted through an online survey for medical students. The participants were students attending medical schools nationwide, and the final analysis target was 678. The survey developed questionnaires necessary for research purposes regarding global health-related experiences and perceptions, level of awareness of global health competencies (GHC), and needs assessments. The data were analyzed using the frequency analysis, chi-square test, independent t-test, Borich Needs Assessment Model, and the Locus for Focus Model. RESULTS: In total, 60.6% (411/678) agreed on the need for GHE, whereas 12.1% (82/678) agreed on the appropriateness of GHE in the current medical school curriculum, indicating a perception gap between the necessity and the status. At the current level of awareness of global health and GHC, we identified statistically significant differences according to gender, participation in global health activities, and GHE. In the analysis of the educational needs of GHC, all items of GHC had statistically significant differences between the importance level and the current level, and priorities were derived. The competency with the highest priority was domain A (Global Burden of Disease). CONCLUSION: We expect the findings of this study to be used in Korean medical education as fundamental data to prepare a hereafter research foundation for GHE and discuss systematic GHE based on GHC.

Consensus on global health competencies for Korean medical students using a modified Delphi method.

PURPOSE: This study aimed to reach a consensus among experts on the global health competencies for medical students in Korea. METHODS: A global health competency model was developed to identify domains and competencies for medical education, and a three-round modified Delphi method was used to reach consensus among 21 experts on the essential global health competencies. The degree of convergence, degree of consensus, and content validity ratio of the model were used to reach a consensus. RESULTS: A list of 52 competencies in 12 domains were identified according to a literature review. In the first-round Delphi survey, the global health competencies were refined to 30 competencies in eight domains. In the second round, the competencies were reduced to 24. In the final round, consensus was reached among the expert panel members, and the competencies were finalized. The global health competency domains for medical students include global burden of disease (three items), globalization of health and healthcare (five items), determinants of health (two items), healthcare in low-resource settings (two items), global health governance (three items), health as a human right (four items), cultural diversity and health (three items), and participation in global health activities (two items). CONCLUSION: The group of experts in global health achieved a consensus that 24 global health competencies in eight domains were essential for undergraduate medical education in Korea. The domains and competencies identified herein can be used to develop an undergraduate medical education curriculum in global health.

Metabolic Disorders Are Associated With Drug-Induced Liver Injury During Antituberculosis Treatment: A Multicenter Prospective Observational Cohort Study in Korea.

Background: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT. Methods: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated. Results: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders. Conclusions: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

Validation of the Korean version of the Reflective Practice Questionnaire in clinical clerkship of Korean medical students.

PURPOSE: This study aims to verify whether the Reflective Practice Questionnaire (RPQ) developed by Priddis and Rogers is valid in the Korean context to identify the level of reflection of medical students in clinical practice. METHODS: A total of 202 third- and fourth-year medical students from seven universities participated in the study. After receiving approval for use from the authors, a survey was conducted on the students through an adaptation process. The original scale consists of 10 factors with 40 items. The Self-efficacy in Clinical Performance Scale (SECP), Korean Self-reflection and Insight Scale (K-SRIS), and Reflection-in-Learning Scale (RinLS) were used to validate the scale. Exploratory factor, confirmatory factor, correlation, and reliability analyses were used for data analysis. RESULTS: As a result of exploratory factor analysis, 10 subfactors were extracted (Kaiser-Meyer-Olkin=0.856, Bartlett's test: χ 2 =5,044.337, degrees of freedom=780, p<0.001). Among the 40 items, one that showed a high overlapping load for other factors was excluded. As a result of confirmatory factor analysis, the 10-factor structure model was found suitable (χ 2 =1.980, comparative fit index=0.859, Tucker-Lewis index=0.841, root mean square error of approximation=0.070). As a result of the criterion validity test, most of the subfactors of the Korean version of the RPQ (K-RPQ) showed a positive correlation with K-SRIS, RinLS, and SECP. The reliability of 10 subfactors was satisfactory, ranging from 0.666 to 0.919. CONCLUSION: The K-RPQ was confirmed to be a reliable and valid tool to evaluate the level of reflection among Korean medical students in clinical clerkship. This scale can be used as a tool to provide feedback on each student's level of reflection in clinical clerkship.

Latent profile analysis of adaptation types and stress among medical students during the COVID-19 pandemic in South Korea.

Objective: This study aimed to identify profile groups based on personality traits and coping strategies exhibited by medical students in the context of COVID-19. Methods: We conducted a cross-sectional survey and latent profile analysis to investigate differences in stressors, psychological distress, and stress levels with academic variables. We collected data online (Google survey form) in November and December 2021. The participants included a total of 260 1st and 2nd year medical students, all completed questionnaires containing the following sections: Big Five Inventory, coping strategies, COVID-19 stressors, Kessler Psychological Distress Scale, and stress level with academic variables. For analysis, a latent profile analysis, ANOVA, and χ2 were used. Results: The results reveal the three following profile groups: adaptive (lowest neuroticism, low mental disengagement), middle-adaptive (moderate neuroticism, low mental disengagement), and maladaptive (highest neuroticism and mental disengagement), respectively comprising 25.0%, 39.2%, and 35.8% of the study sample. There were no statistically significant intergroup differences regarding grade (χ2=3.345, p=0.188) or gender (χ2=1.197, p=0.550). The maladaptive group was strongly associated with perceived stress during the COVID-19 pandemic (p<0.001). Conclusion: These findings highlight the value of considering profile groups when determining whether students require additional support during pandemics.

Adverse Effects of Air Pollution on Pulmonary Diseases.

Environmental exposure to air pollution is known to have adverse effects on various organs. Air pollution has greater effects on the pulmonary system as the lungs are directly exposed to contaminants in the air. Here, we review the associations of air pollution with the development, morbidity, and mortality of pulmonary diseases. Short- and long-term exposure to air pollution have been shown to increase mortality risk even at concentrations below the current national guidelines. Ambient air pollution has been shown to be associated with lung cancer. Particularly long-term exposure to particulate matter with a diameter <2.5 µm (PM2.5) has been reported to be associated with lung cancer even at low concentrations. In addition, exposure to air pollution has been shown to increase the incidence risk of chronic obstructive pulmonary disease (COPD) and has been correlated with exacerbation and mortality of COPD. Air pollution has also been linked to exacerbation, mortality, and development of asthma. Exposure to nitrogen dioxide (NO2) has been demonstrated to be related to increased mortality in patients with idiopathic pulmonary fibrosis. Additionally, air pollution increases the incidence of infectious diseases, such as pneumonia, bronchitis, and tuberculosis. Furthermore, emerging evidence supports a link between air pollution and coronavirus disease 2019 transmission, susceptibility, severity and mortality. In conclusion, the stringency of air quality guidelines should be increased and further therapeutic trials are required in patients at high risk of adverse health effects of air pollution.

miRNA-6515-5p regulates particulate matter-induced inflammatory responses by targeting CSF3 in human bronchial epithelial cells.

Particulate matter (PM) is associated with the incidence, exacerbation, and mortality of variable respiratory diseases. However, the molecular mechanisms of PM10-mediated inflammation are unclear. We identified microRNAs (miRNAs) and messenger RNAs (mRNAs) related to the inflammatory response in PM10-exposed bronchial epithelial cells using next-generation sequencing. Of the miRNAs, miR-6515-5p was significantly downregulated in PM10-exposed human bronchial epithelial BEAS-2B cells. miR-6515-5p regulated the production of pro-inflammatory cytokines (IL-6 and IL-8) and the expression of inflammatory genes (IL-1ß, IL-6, IL-8, TNF-α, CXCL-1, and MCP-1) via MAPK/ERK signaling; overexpression of miR-6515-5p using a mimic inhibited PM10-induced inflammatory responses via inactivation of the ERK pathway, whereas downregulation of miR-6515-5p via an inhibitor significantly increased inflammation in PM10-exposed cells via activation of ERK. Furthermore, we identified colony stimulating factor 3 (CSF3) as a target gene of miR-6515-5p using TargetScanHuman, and confirmed the association between miR-6515-5p and CSF3 using a luciferase reporter assay. Furthermore, we found that mRNA and protein levels of CSF3 were negatively regulated by miR-6515-5p. Inhibition of CSF3 by small interfering RNA significantly reduced the expression and production of inflammatory markers in PM10-exposed cells by inactivating the MAPK/ERK signaling pathway. Therefore, we suggest that miR-6515-5p regulates PM10-induced inflammatory responses by targeting CSF3 via MAPK/ERK signaling in bronchial epithelial cells.

Histone deacetylase 3 promotes alveolar epithelial-mesenchymal transition and fibroblast migration under hypoxic conditions.

Epithelial-mesenchymal transition (EMT), a process by which epithelial cells undergo a phenotypic conversion that leads to myofibroblast formation, plays a crucial role in the progression of idiopathic pulmonary fibrosis (IPF). Recently, it was revealed that hypoxia promotes alveolar EMT and that histone deacetylases (HDACs) are abnormally overexpressed in the lung tissues of IPF patients. In this study, we showed that HDAC3 regulated alveolar EMT markers via the AKT pathway during hypoxia and that inhibition of HDAC3 expression by small interfering RNA (siRNA) decreased the migration ability and invasiveness of diseased human lung fibroblasts. Furthermore, we found that HDAC3 enhanced the migratory and invasive properties of fibroblasts by positively affecting the EMT process, which in turn was affected by the increased and decreased levels of microRNA (miR)-224 and Forkhead Box A1 (FOXA1), respectively. Lastly, we found this mechanism to be valid in an in vivo system; HDAC3 siRNA administration inhibited bleomycin-induced pulmonary fibrosis in mice. Thus, it is reasonable to suggest that HDAC3 may accelerate pulmonary fibrosis progression under hypoxic conditions by enhancing EMT in alveolar cells through the regulation of miR-224 and FOXA1. This entire process, we believe, offers a novel therapeutic approach for pulmonary fibrosis.

Effects of antioxidants on oxidative stress and inflammatory responses of human bronchial epithelial cells exposed to particulate matter and cigarette smoke extract.

Particulate matter (PM) is a type of air pollutant that induces adverse health effects, including acute exacerbation of chronic obstructive pulmonary disease (COPD). However, the effects of co-exposure to PM and cigarette smoke extract (CSE) on bronchial epithelial cells remain unknown. This study investigated the cytotoxic and pro-inflammatory effects of combined exposure to PM and CSE on bronchial epithelial cells, and assessed the potential of antioxidants to inhibit CSE/PM-induced oxidative stress and inflammation. Exposure of epithelial cells to PM or CSE induced cytotoxicity, inflammation, and oxidative stress, all of which were dramatically increased when cells were exposed to the combination of CSE and PM. Importantly, the adverse effects of CSE/PM exposure were suppressed when cells were treated with sulforaphane (SFN) or sulforaphane N-acetylcysteine (SFNAC). Furthermore, SFN and SFNAC suppressed the CSE/PM-induced pro-inflammatory cytokine production and expression of inflammatory genes. Combined PM and CSE exposure further activated the MAPK and Nrf2 signaling pathways. SFN and SFNAC attenuated CSE/PM-induced epithelial toxicity through the ERK/JNK signaling pathway-dependent inhibition of inflammation. Moreover, SFN and SFNAC suppressed ROS generation by activating antioxidant enzymes and Nrf2 signaling. Therefore, SFN and SFNAC could be a promising approach to prevent or mitigate the exacerbation of pulmonary diseases caused by PM and other air pollutants.

Particulate-Matter Related Respiratory Diseases.

Particulate matter (PM) is suspended dust that has a diameter of <10 µm and can be inhaled by humans and deposited in the lungs, particularly the alveoli. Recent studies have shown that PM has an adverse effect on respiratory diseases. The aim of this article is to review respiratory diseases associated with PM. According to existing studies, PM is associated with chronic obstructive pulmonary disease, bronchial asthma, and several other respiratory diseases and increases the mortality rates of these diseases. Moreover, increased exposure in the high concentration of atmospheric PM is associated with the development of lung cancer. The most simple and common way to protect an individual from airborne PM is to wear a face mask that filters out PM. In areas of high concentration PM, it is recommended to wear a face mask to minimize the exposure to PM. However, the use of N95 or KF94 masks can interfere with respiration in patients with chronic respiratory diseases who exhibit low pulmonary function, leading to an increased risk of respiratory failure. Conclusionally, reduction of the total amount of PM is considered to be important factor and strengthening the national warning notification system to vulnerable patients and proper early management of exacerbated patients will be needed in the future.

Risks of N95 Face Mask Use in Subjects With COPD.

BACKGROUND: The N95 filtering facepiece respirator (FFR) is the most popular individual protective device to reduce exposure to particulate matter. However, concerns have been raised with regard to its use because it can increase respiratory resistance and dead space. Therefore, this study assessed the safety of N95 use in patients with COPD and air-flow limitation. METHODS: This prospective study was performed at a tertiary hospital and enrolled 97 subjects with COPD. The subjects were monitored for symptoms and physiologic variables during a 10-min rest period and 6-min walking test while wearing an N95. RESULTS: Of the 97 subjects, 7 with COPD did not wear the N95 for the entire test duration. This mask-failure group showed higher British modified Medical Research Council dyspnea scale scores and lower FEV1 percent of predicted values than did the successful mask use group. A modified Medical Research Council dyspnea scale score ≥ 3 (odds ratio 167, 95% CI 8.4 to >999.9; P = .008) or a FEV1 < 30% predicted (odds ratio 163, 95% CI 7.4 to >999.9; P = .001) was associated with a risk of failure to wear the N95. Breathing frequency, blood oxygen saturation, and exhaled carbon dioxide levels also showed significant differences before and after N95 use. CONCLUSIONS: This study demonstrated that subjects with COPD who had modified Medical Research Council dyspnea scale scores ≥ 3 or FEV1 < 30% predicted wear N95s only with care.

Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells.

BACKGROUND: Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food. METHODS: To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells. RESULTS: We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4'6'-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways. CONCLUSIONS: CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.

Exacerbations of Chronic Obstructive Pulmonary Disease Tool to assess the efficacy of acute treatment.

BACKGROUND AND OBJECTIVE: The Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Patient-Reported Outcomes (EXACT-PRO) has been suggested as a reliable and valid measure for early assessment of COPD exacerbations and perceived recovery. However, there has been no evidence for EXACT-PRO efficacy in assessing recovery from treatment in a randomized controlled trial. The study evaluated the reliability, validity, and responsiveness of EXACT-PRO for the evaluation of the efficacy of acute treatment in patients with COPD exacerbation. METHODS: In a Phase III randomized controlled study for assessing the efficacy of antibiotic treatment on COPD exacerbation, EXACT-PRO was evaluated in the responders and non-responders. RESULTS: A total of 295 patients were analyzed (259 responders and 37 non-responders). Cronbach's α was 0.96 for EXACT total, 0.96 for the breathlessness domain, 0.89 for the cough and sputum domain, and 0.93 for the chest symptoms domain. The EXACT score correlated with the COPD assessment test (CAT) score (r=0.8, P<0.01). A stronger decrease in the EXACT score was found in the responder group than in the non-responder group from the fifth day after treatment. The difference in the EXACT score from exacerbation onset to recovery was -6.3 in responders and -1.9 in non-responders (P=0.01). CONCLUSION: EXACT-PRO is a comprehensive and sensitive method for assessing symptomatic resolution of COPD exacerbations during treatment.

Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-ß1-induced model and an in vivo bleomycin (BLM)-induced model. METHODS: In vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-ß1-induced EMT and fibrosis were assessed using western blotting and a quantitative real-time polymerase chain reaction. The lungs were analyzed histopathologically in vivo using hematoxylin and eosin and Masson's trichrome staining. The BLM-induced fibrosis was characterized by western blotting and immunohistochemical analyses for fibronectin, TGF-ß1, E-cadherin (E-cad), and α-smooth muscle actin (SMA) in lung tissues. RESULTS: SFN reversed mesenchymal-like changes induced by TGF-ß1 and restored cells to their epithelial-like morphology. The results confirmed that the expression of the epithelial marker, E-cadherin, increased after SFN treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and α-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-ß1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-ß1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and α-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-ß1-induced phosphorylation of SMAD2/3 protein in A549 cells and MRC-5 cells. BLM induced fibrosis in mouse lungs that was also attenuated by SFN treatment, and SFN treatment decreased BLM-induced fibronectin expression, TGF-ß1 expression, and the levels of collagen I in the lungs of mice. CONCLUSIONS: SFN showed a significant anti-fibrotic effect in TGF-ß-treated cell lines and BLM-induced fibrosis in mice. These findings showed that SFN has anti-fibrotic activity that may be considered in the treatment of IPF.

The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells.

BACKGROUND: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. METHODS: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. RESULTS: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. CONCLUSION: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy.

Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases.

Dust particles-induced intracellular Ca2+ signaling and reactive oxygen species in lung fibroblast cell line MRC5.

Epidemiologic interest in particulate matter (PM) is growing particularly because of its impact of respiratory health. It has been elucidated that PM evoked inflammatory signal in pulmonary epithelia. However, it has not been established Ca2+ signaling mechanisms involved in acute PM-derived signaling in pulmonary fibroblasts. In the present study, we explored dust particles PM modulated intracellular Ca2+ signaling and sought to provide a therapeutic strategy by antagonizing PM-induced intracellular Ca2+ signaling in human lung fibroblasts MRC5 cells. We demonstrated that PM10, less than 10 µm, induced intracellular Ca2+ signaling, which was mediated by extracellular Ca2+. The PM10-mediated intracellular Ca2+ signaling was attenuated by antioxidants, phospholipase blockers, polyADPR polymerase 1 inhibitor, and transient receptor potential melastatin 2 (TRPM2) inhibitors. In addition, PM-mediated increases in reactive oxygen species were attenuated by TRPM2 blockers, clotrimazole (CLZ) and N-(p-amylcinnamoyl) anthranilic acid (ACA). Our results showed that PM10 enhanced reactive oxygen species signal by measuring DCF fluorescence and the DCF signal attenuated by both TRPM2 blockers CLZ and ACA. Here, we suggest functional inhibition of TRPM2 channels as a potential therapeutic strategy for modulation of dust particle-mediated signaling and oxidative stress accompanying lung diseases.

A Pilot Study of Intralymphatic Immunotherapy for House Dust Mite, Cat, and Dog Allergies.

Several recent clinical trials reported that intralymphatic immunotherapy (ILIT) for some allergens, such as cat dander and pollen, induce tolerance more rapidly than conventional subcutaneous or sublingual immunotherapy, have a comparable duration of effect after only 3 injections, and do not provoke serious local or systemic reactions. However, the efficacy and safety of ILIT are using Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dp), and dog, which are indoor allergens that are commonly found globally, need to be evaluated. Furthermore, use of multiple allergens in ILIT should be investigated. We assessed the clinical efficacy and adverse effects of ILIT using aqueous Df, Dp, dog, and cat allergens or mixtures thereof in patients with allergic rhinitis. A total of 11 subjects with AR sensitized to Df, Dp, cat, and/or dog allergens received 3 intralymphatic inguinal injections of sensitized allergen extract (HollisterStier, New Orleans, LA, USA). Clinical parameters were assessed before ILIT, and 4 months and 1 year after the first injection. Rhinitis symptoms were alleviated and quality of life was improved 4 months after ILIT (P=0.012 and P=0.007, respectively), and these improvements lasted for 1 year after ILIT (P=0.047 and P=0.009, respectively). However, we observed 2 cases of anaphylaxis, one case of a moderate-to-severe systemic hypersensitivity reaction and the other case of a severe local reaction at the injection site after ILIT. In conclusion, ILIT can rapidly improve allergy symptoms and quality of life, and this effect lasts for 1 year. In hypersensitized patients, however, ILIT can provoke severe systemic and/or local hypersensitivity reactions when performed using aqueous allergen extracts.

Perceived Social Support as a Determinant of Quality of Life Among Medical Students: 6-Month Follow-up Study.

OBJECTIVE: This longitudinal study aimed to identify the relevant factors related to quality of life (QoL) changes in medical students. METHODS: For this 6-month follow-up study, we enrolled 109 students from a Korean medical school. To assess students' QoL, we used the World Health Organization QoL scale. Possible determinants of student QoL included demographics, fatigue, and social support. A stepwise multivariate analysis identified factors associated with changes of student QoL. RESULTS: Among sources of support, the "friends" category was the main position affecting their overall QoL, and "significant other" had the strongest influence on psychological and social domains. The impact of support from friends on QoL was confirmed in the longitudinal analysis. Final regression models revealed that providing students with more social support and promoting fatigue reduction best improved medical student sense of well-being. CONCLUSION: Creating stronger student support programs to prevent social detachment and implementing strategies to reduce fatigue can improve QoL in medical students.