Extracellular Vesicles Released by Lactobacillus paracasei Mitigate Stress-induced Transcriptional Changes and Depression-like Behavior in Mice

Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of “responses to stress or steroid hormones”, “histone modification”, and “regulating MAPK signaling pathways”. While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.

Report on the methacholine bronchial provocation test protocol: An updated statement of Korean Academy of Asthma, Allergy and Clinical Immunology

The Korean Academy of Asthma, Allergy, and Clinical Immunology task force report aims to provide new protocols for methacholine challenge test (MCT). Although new devices have different delivery system compared to old ones, previous protocols are still used, which cannot guarantee adequate diagnoses of asthma. Another important issue is the recent recommendation in European Respiratory Society (ERS) technical standard guideline to use a delivered methacholine dose that causes a 20% decrease in forced expiratory volume in 1 second (FEV1) (PD 20). Although the previous protocol based on the methacholine concentration causing a 20% decrease in FEV1 (PC 20) has been used globally, several studies have reported that PD 20 is more reliable and applicable for new protocols of MCT. Indeed, a tidal breathing inhalation protocol using a breath-actuated or continuous nebulizer is recommended. Herein, we recommend 3 protocols for the MCT using new devices and provide a brief summary of the change in strategy based on the updated ERS guideline.

A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea / 결핵및호흡기질환

Background@#Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. @*Methods@#A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. @*Results@#We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). @*Conclusion@#Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Extracellular vesicles derived from small intestinal lamina propria reduce antigen-specific immune response

Background/Aims@#Extracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs. @*Methods@#LpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance. @*Results@#The isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner. @*Conclusions@#EVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.

N-Acetylcysteine Induces Apoptotic, Oxidative and Excitotoxic Neuronal Death in Mouse Cortical Cultures / 전남의대학술지

N-acetylcysteine (NAC) has been used as an antioxidant to prevent oxidative cell death.However, we found NAC itself to induce neuronal death in mouse cortical cultures.Therefore, the current study was performed to investigate the mechanism of neuronal death caused by NAC. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media after 24-48 h exposure to NAC. NAC (0.1-10 mM) induced neuronal death in a concentration- and exposure time-dependent manner. However, NAC did not injure astrocytes even at a concentration of 10 mM. Also, 10 mM NAC markedly attenuated oxidative astrocyte death induced by 0.5 mM diethyl maleate or 0.25 mM H2O2 . The NMDA receptor antagonist MK-801 (10 μM) markedly attenuated the neuronal death caused by 10 mM NAC, while NBQX did not affect the neuronal death. Cycloheximide (a protein synthesis inhibitor, 0.1 μg/mL) and z-VAD-FMK (a caspase inhibitor, 100 μM) also significantly attenuated neuronal death. Apoptotic features such as chromatin condensation, nuclear fragmentation, and caspase 3 activation were observed 1 h after the NAC treatment. The neuronal death induced by 1 or 10 mM NAC was significantly attenuated by the treatment with 100 μM Trolox or 1 mM ascorbic acid. NAC induced the generation of intracellular reactive oxygen species (ROS), as measured by the fluorescent dye 2’,7’-dichlorofluorescein diacetate. The ROS generation was almost completely abolished by treatment with Trolox or ascorbic acid. These findings demonstrate that NAC can cause oxidative, apoptotic, and excitotoxic neuronal death in mouse neuronal cultures.

Licochalcone H Induces Cell Cycle Arrest and Apoptosis in Human Skin Cancer Cells by Modulating JAK2/STAT3 Signaling

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

Clinical Characteristics of Patients Who Contracted the SARS-CoV-2 Omicron Variant from an Outbreak in a Single Hospital

There are few studies on the severity and prognosis of patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) omicron variant. From January 11, 2022 to January 25, 2022, 181 patients were infected with the SARS-CoV-2 omicron variant in a single hospital in Korea. The initial clinical characteristics were investigated through the COVID-19 basic investigation form. Outcomes were reviewed using medical records. The median age of the patients was 57 years (range 1–90), and 95 patients (52.5%) were male. None were re-infected with SARS-CoV-2, and 127 (70.2%) were fully vaccinated (boosted or within 6 months after second vaccination). Forty-two patients (23.2%) were asymptomatic. Among symptomatic patients, the frequency of symptoms was as follows: cough (37.0%), sore throat (33.7%), and fever (30.4%). In terms of disease severity, 168 (92.8%) patients did not require supplemental oxygen, 6 (3.3%) required low-flow oxygen, 5 (2.8%) required high-flow oxygen, and 2 (1.1%) died. Four of the five individuals who required high-flow oxygen and the two who died were not vaccinated. Most of the patients who contracted the SARS-CoV-2 omicron variant exhibited mild clinical features; however, severe clinical features including mortality were encountered among individuals who were not vaccinated.

Dysphagia Aortica Initially Misdiagnosed as Poststroke Dysphagia: A Case Report / 대한연하장애학회지

Dysphagia aortica is a rare form of mechanical dysphagia characterized by extrinsic compression of the esophagus by the aorta. A 69-year-old male reported experiencing swallowing difficulties for five months, along with nausea, abdominal discomfort, weight loss, and severe reflux. Considering his age and a medical history of hypertension and stenosis of the cerebral artery, poststroke dysphagia was initially suspected. However, brain magnetic resonance imaging revealed no evidence of acute or subacute stroke. Further evaluation was achieved via enhanced chest computed tomography to locate the focus of the systemic inflammation. A thoracic aortic aneurysm about 8.7×5.0 cm in size, with signs of impending rupture, was observed. This case reinforces that a high possibility for dysphagia aortica should be considered under conditions of unclear etiology of dysphagia but the presence of associated symptoms, such as progressive intolerance to solids and ultimately to liquids, weight loss, and nausea.

Clinical Manifestations and Maternal and Perinatal Outcomes in Pregnancy Following Laboratory-Confirmed SARS-CoV-2 Infection in South Korea

Purpose@#To determine the clinical manifestations and maternal and perinatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19). @*Methods@#We conducted a retrospective observational study of pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to National Health Insurance Service (NHIS) Ilsan Hospital between August 2020 and October 2021. The maternal and perinatal outcomes were investigated. @*Results@#Among 184 pregnant women infected with SARS-CoV-2, 79 women delivered. Of the women who delivered, with 36 women giving birth during the quarantine period. At delivery, 45 women were positive for SARS-CoV-2 by polymerase chain reaction (PCR), whereas 34 women were negative. The most common clinical manifestations were cough (65.2%), fever (38.0%), and myalgia (33.2%). Regarding perinatal outcomes, none of the babies had an Apgar score <7 at 5 minutes, and none were intubated following the delivery. The preterm birth rate and small-for-gestational-age (SGA) rate were 15.2% and 16.5%, respectively. All babies who was delivered at NHIS Ilsan Hospital were negative for SARS-CoV-2 infection by PCR, which was evaluated using amniotic fluid, cord blood, neonatal nasopharyngeal and oropharyngeal swabs in the 1st and 2nd days following delivery, although 45 women were positive for SARS-CoV-2 infection by PCR at the time of delivery. @*Conclusion@#Most pregnant women with COVID-19 in South Korea were unlikely to manifest symptoms or present with a severe disease progression. The observed preterm birth rate and SGA rate were higher in women with COVID-19 than in those without COVID-19. However, there was no evidence of vertical transmission, and all babies were negative for SARS-CoV-2 infection during pregnancy.

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background/Aims@#Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model. @*Methods@#A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model. @*Results@#PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF. @*Conclusions@#Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.

Patterns of medical care utilization according to environmental factors in asthma and chronic obstructive pulmonary disease patients

Background/Aims@#Weather and air pollution are associated with the exacerbation of respiratory diseases. We investigated patterns of medical care use according to meteorological factors and air pollution in patients with asthma or chronic obstructive pulmonary disease (COPD). @*Methods@#We analyzed the medical care utilization patterns of patients with asthma or COPD registered in the Korea Health Insurance Review and Assessment database for the period 2007 to 2013. The patterns were divided into hospitalization and emergency department (ED) use. @*Results@#The medical care use of patients with asthma or COPD increased when the mean temperature and relative humidity were lower, and the temperature difference and atmospheric pressure were greater. Medical care use increased with the concentrations of particulate matter and ozone. Among age groups, sensitivity to pollutants was greatest in patients aged ≥ 65 years. The effect of being elderly was greater for asthma than for COPD, with a higher hospitalization rate. ED utilization affected by environmental factors was significantly greater for females and hospitalization was significantly more common for males. @*Conclusions@#Meteorological factors and air pollutants were shown to contribute to increased medical care utilization by patients with asthma and COPD, particularly elderly patients. The overall effect was greater for COPD, but the effect in elderly patients was greater for asthma. In addition, the patterns of change in medical care use due to environmental factors differed according to sex.

Continued Upward Trend in Non-Tuberculous Mycobacteria Isolation over 13 Years in a Tertiary Care Hospital in Korea

Purpose@#Despite decreased prevalence of tuberculosis, the incidence of the diseases associated with nontuberculous mycobacteria (NTM) has been increasing in South Korea and around the world. The present retrospective study was conducted to determine longitudinal changes in the epidemiology and distribution of NTM over 13 years at a tertiary care hospital in Korea. @*Materials and Methods@#We retrospectively analyzed data on Mycobacterium species over 13 years (January 2007 to December 2019) by utilizing the laboratory information system. Mycobacterium species were identified using biochemical tests and PCR-restriction fragment length polymorphism and Mycobacteria GenoBlot assays. @*Results@#After excluding duplicates from the initial pool of 17996 mycobacterial isolates, 7674 strains were analyzed and 2984 (38.9%) NTM were isolated. The proportion of NTM continuously increased over the 13-year period, from 17.0% in 2007 to 57.5% in 2019. Among the NTM isolates, the most common species were Mycobacterium intracellulare (50.6%), M. avium (18.3%), M. fortuitum complex (4.9%), M. abscessus (4.5%), M. gordonae (3.3%), M. kansasii (1.1%), M. chelonae (1.0%), and M. massiliense (0.9%).In patients over the age of 70 years, the proportion of NTM among the isolates increased from 26.6% in 2007 to 62.0% in 2019, and that of M. intracellulare isolates among the NTM increased from 13.9% (11/79) in 2007 to 37.4% (175/468) in 2019. @*Conclusion@#The number of NTM isolates continuously increased over the study period, and the increase in the proportion of M. intracellulare in patients aged over 70 years was notable.

Patterns of medical care utilization according to environmental factors in asthma and chronic obstructive pulmonary disease patients

Background/Aims@#Weather and air pollution are associated with the exacerbation of respiratory diseases. We investigated patterns of medical care use according to meteorological factors and air pollution in patients with asthma or chronic obstructive pulmonary disease (COPD). @*Methods@#We analyzed the medical care utilization patterns of patients with asthma or COPD registered in the Korea Health Insurance Review and Assessment database for the period 2007 to 2013. The patterns were divided into hospitalization and emergency department (ED) use. @*Results@#The medical care use of patients with asthma or COPD increased when the mean temperature and relative humidity were lower, and the temperature difference and atmospheric pressure were greater. Medical care use increased with the concentrations of particulate matter and ozone. Among age groups, sensitivity to pollutants was greatest in patients aged ≥ 65 years. The effect of being elderly was greater for asthma than for COPD, with a higher hospitalization rate. ED utilization affected by environmental factors was significantly greater for females and hospitalization was significantly more common for males. @*Conclusions@#Meteorological factors and air pollutants were shown to contribute to increased medical care utilization by patients with asthma and COPD, particularly elderly patients. The overall effect was greater for COPD, but the effect in elderly patients was greater for asthma. In addition, the patterns of change in medical care use due to environmental factors differed according to sex.

Continued Upward Trend in Non-Tuberculous Mycobacteria Isolation over 13 Years in a Tertiary Care Hospital in Korea

Purpose@#Despite decreased prevalence of tuberculosis, the incidence of the diseases associated with nontuberculous mycobacteria (NTM) has been increasing in South Korea and around the world. The present retrospective study was conducted to determine longitudinal changes in the epidemiology and distribution of NTM over 13 years at a tertiary care hospital in Korea. @*Materials and Methods@#We retrospectively analyzed data on Mycobacterium species over 13 years (January 2007 to December 2019) by utilizing the laboratory information system. Mycobacterium species were identified using biochemical tests and PCR-restriction fragment length polymorphism and Mycobacteria GenoBlot assays. @*Results@#After excluding duplicates from the initial pool of 17996 mycobacterial isolates, 7674 strains were analyzed and 2984 (38.9%) NTM were isolated. The proportion of NTM continuously increased over the 13-year period, from 17.0% in 2007 to 57.5% in 2019. Among the NTM isolates, the most common species were Mycobacterium intracellulare (50.6%), M. avium (18.3%), M. fortuitum complex (4.9%), M. abscessus (4.5%), M. gordonae (3.3%), M. kansasii (1.1%), M. chelonae (1.0%), and M. massiliense (0.9%).In patients over the age of 70 years, the proportion of NTM among the isolates increased from 26.6% in 2007 to 62.0% in 2019, and that of M. intracellulare isolates among the NTM increased from 13.9% (11/79) in 2007 to 37.4% (175/468) in 2019. @*Conclusion@#The number of NTM isolates continuously increased over the study period, and the increase in the proportion of M. intracellulare in patients aged over 70 years was notable.

Retinol-binding protein-4 was associated with sensitization to inhalant allergens in the elderly population

Background/Aims@#Recent evidence suggests an association between allergic sensitization and metabolic markers. However, this association has rarely been examined in the elderly. Retinol-binding protein-4 (RBP-4) is a recently identified adipokine that acts on the muscle and liver affecting insulin sensitivity. We evaluated the association between metabolic parameters and allergic sensitization in the elderly. @*Methods@#We analysed the database of the Korean Longitudinal Study on Health and Aging cohort study conducted during 2005 to 2006. Atopy was identified by inhalant allergen skin prick test. Metabolic conditions were assessed using anthropometric indices and serum biomarkers such as fasting glucose, lipid, adiponectin, and RBP-4. @*Results@#Among the 854 elderly subjects, 17.2% had atopy. Plasma RBP-4 levels were significantly higher in the atopic elderly than nonatopic elderly (p = 0.003). When RBP-4 percentiles were categorized as under three groups, the prevalence of atopy and current rhinitis increased significantly with percentiles of RBP-4 levels (p = 0.019 and p = 0.007, respectively). Log RBP-4 was associated with atopy (odds ratio [OR], 4.10; p = 0.009) and current rhinitis (OR, 2.73; p = 0.014), but not with current asthma (OR, 1.17; p = 0.824). Higher RBP-4 level in atopic elderly was also observed in current rhinitis patients. Atopy, but not current rhinitis, showed significant relationships with log RBP-4 levels in multivariate analyses adjusted for other metabolic markers including body mass index. @*Conclusions@#RBP-4 positively associated with atopy in the general elderly population irrespective of other metabolic markers.

Respiratory Arrest Induced by Presbyesophagus: A Case Report / 대한연하장애학회지

Presbyesophagus is a unique cause of dysphagia in the elderly, which features incomplete relaxation of the lower esophageal sphincter, dilatation of the esophagus, decreased esophageal peristaltic pressures, abnormal esophageal contractions, and delayed emptying of the esophagus. An 88-year-old woman underwent surgery for a femur fracture.The day after surgery, respiratory arrest occurred during a meal. Breathing resumed after oxygen supply with airway opening. She complained of dysphagia and nausea during a meal, and the videofluoroscopic swallowing study and esophagography showed delayed emptying of the esophagus, abnormal esophageal contraction, and dilatation of the esophagus. This case shows that esophageal dysfunction in the elderly with poor general medical conditions can worsen abruptly.

Update on genetic screening and treatment for infertile men with genetic disorders in the era of assisted reproductive technology / 대한생식의학회지

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.

4-Hexylresorcinol induced angiogenesis potential in human endothelial cells / 대한악안면성형재건외과학회지

Background@#4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. @*Methods@#As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. @*Results@#Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. @*Conclusion@#Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles

Purpose@#Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. @*Methods@#We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. @*Results@#Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. @*Conclusions@#The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.