Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair.

Reactive oxygen species (ROS) generate oxidized bases and single-strand breaks (SSBs), which are fixed by base excision repair (BER) and SSB repair (SSBR), respectively. Although excision and repair of damaged bases have been extensively studied, the function of the sliding clamp, proliferating cell nuclear antigen (PCNA), including loading/unloading, remains unclear. We report that, in addition to PCNA loading by replication factor complex C (RFC), timely PCNA unloading by the ATPase family AAA domain-containing protein 5 (ATAD5)-RFC-like complex is important for the repair of ROS-induced SSBs. We found that PCNA was loaded at hydrogen peroxide (H2O2)-generated direct SSBs after the 3'-terminus was converted to the hydroxyl moiety by end-processing enzymes. However, PCNA loading rarely occurred during BER of oxidized or alkylated bases. ATAD5-depleted cells were sensitive to acute H2O2 treatment but not methyl methanesulfonate treatment. Unexpectedly, when PCNA remained on DNA as a result of ATAD5 depletion, H2O2-induced repair DNA synthesis increased in cancerous and normal cells. Based on higher H2O2-induced DNA breakage and SSBR protein enrichment by ATAD5 depletion, we propose that extended repair DNA synthesis increases the likelihood of DNA polymerase stalling, shown by increased PCNA monoubiquitination, and consequently, harmful nick structures are more frequent.

Remimazolam dose for successful insertion of a supraglottic airway device with opioids: a dose-determination study using Dixon's up-and-down method.

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine, was recently approved in numerous jurisdictions as an induction drug for general anesthesia. We aimed to determine the doses of remimazolam that would allow placement of a supraglottic airway device (SGD) in 50% and 95% of nonparalyzed patients (ED50 and ED95). METHODS: In this prospective study, 30 American Society of Anesthesiology Physical Status I-II grade female patients scheduled for hysteroscopic surgery were enrolled. Anesthesia was induced with 1 µg·kg-1 of fentanyl and continuous infusion of remimazolam without neuromuscular blockade. An i-gel® SGD was inserted 2.5 min after the start of remimazolam infusion. We used Dixon's up-and-down method and isotonic regression to determine the ED50 and ED95 of remimazolam for insertion of an SGD. RESULTS: Twenty-eight patients were included in the final analysis. The ED50 and ED95 of remimazolam required for successful i-gel insertion were 8.8 mg·kg-1·hr-1 (95% confidence interval [CI], 6.3 to 10.6) and 10.7 mg·kg-1·hr-1 (95% CI, 10.6 to 11.7), respectively. A nonfully relaxed jaw was found in 7/13 patients (54%) in the success group and 14/15 patients (93%) in the failure group (difference in proportions, 40%; 95% CI, 7 to 65; P = 0.02). Bucking or other movements during SGD insertion only occurred in the failure group (11/15, 73%). CONCLUSION: In 95% of nonparalyzed female patients undergoing hysteroscopy, 10.7 mg·kg-1·hr-1 of remimazolam with 1 µg·kg-1 of fentanyl facilitates i-gel insertion. Remimazolam showed a high incidence of poor jaw relaxation and bucking or other movements during SGD insertion. STUDY REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006527, https://cris.nih.go.kr ; registered 1 September 2021; principal investigator: Ji Seon Jeong).

RéSUMé: OBJECTIF: Le remimazolam, une benzodiazépine à action ultra-brève, a récemment été approuvé dans de nombreuses juridictions comme agent d'induction pour l'anesthésie générale. Notre objectif était de déterminer les doses de remimazolam qui permettraient l'insertion d'un dispositif supraglottique (DSG) chez 50 % et 95 % des patients non paralysés (DE50 et DE95). MéTHODE: Dans cette étude prospective, 30 patientes de statut physique I-II selon l'American Society of Anesthesiology devant bénéficier d'une chirurgie hystéroscopique ont été recrutées. L'anesthésie a été induite avec 1 µg·kg−1 de fentanyl et une perfusion continue de remimazolam sans bloc neuromusculaire. Un DSG i-gel® a été inséré 2,5 minutes après l'amorce de la perfusion de remimazolam. Nous avons utilisé la méthode de l'escalier de Dixon et la régression isotonique pour déterminer la DE50 et DE95 de remimazolam pour l'insertion d'un DSG. RéSULTATS: Vingt-huit patientes ont été incluses dans l'analyse. Les DE50 et DE95 du remimazolam requises pour une insertion réussie de l'i-gel était de 8,8 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 6,3 à 10,6) et 10,7 mg·kg−1·h−1 (IC 95 %, 10,6 à 11,7), respectivement. Une mâchoire non complètement détendue a été observée chez 7 patientes sur 13 (54 %) dans le groupe d'intubation réussie et chez 14/15 patientes (93 %) dans le groupe d'échec d'intubation (différence de proportions, 40 %; IC 95 %, 7 à 65; P = 0,02). Le fléchissement ou d'autres mouvements pendant l'insertion du DSG ne se sont produits que dans le groupe d'échec de l'induction (11/15, 73 %). CONCLUSION: Chez 95 % des patientes non paralysées bénéficiant d'une hystéroscopie, 10,7 mg·kg−1·h−1 de remimazolam avec 1 µg·kg−1 de fentanyl ont facilité l'insertion d'un dispositif i-gel. Le remimazolam a montré une incidence élevée de mauvaise relaxation de la mâchoire et de fléchissement ou d'autres mouvements lors de l'insertion du DSG. ENREGISTREMENT DE L'éTUDE: Registre des essais cliniques de la République de Corée (KCT0006527, https://cris.nih.go.kr ; enregistrée le 1er septembre 2021; chercheur principal : Ji Seon Jeong).

Effects of infusion tubing line lengths and syringe sizes on infusion system compliance: an experimental study using a syringe-type infusion pump at low flow rate.

Ideally, the flow delivery of an infusion system is proportional only to the rate of mechanical actuation of the syringe pump plunger. However, in the real world, overall infusion system compliance may be affected by components such as an extension of tubing lines, or different sizes of syringes. With higher compliance, there may be greater chances of flow irregularity. In this experimental study, we investigated the effects of lengths of infusion lines and syringe sizes on the compliance of syringe pumps with low flow rate (2 ml h-1). In the first experiment, infusion system compliance was measured in various settings by occlusion release. As the infusion tubing length and size of the syringe increased, the time to reach each pressure was delayed and the infusion system compliance increased. The contributions to system compliance from syringes were significantly greater compared to those of extended infusion lines. In the occlusion alarm experiment, the occlusion alarm could be delayed by 69.76 ± 3.98 min for the 50-ml syringe with a 560 cm infusion line set-up. In conclusion, the compliance of a syringe pump system increases as the loaded syringe size, or the length of the infusion tubing increases. The occlusion alarm may be much delayed and not useful in highly compliant systems with respect to the potential occlusion of the infusion system, so more attention is required when using a highly compliant infusion system.

Biopatterned Reorganization of Alkaloids Enabled by Ring-Opening Functionalization of Tertiary Amines.

Biosynthetic processes often involve reorganization of one family of natural products to another. Chemical emulation of nature's rearrangement-based structural diversification strategy would enable the conversion of readily available natural products to other value-added secondary metabolites. However, the development of a chemical method that can be universally applied to structurally diverse natural products is nontrivial. Key to the successful reorganization of complex molecules is a versatile and mild bond-cleaving method that correctly places desired functionality, facilitating the target synthesis. Here, we report a ring-opening functionalization of a tertiary amine that can introduce desired functionalities in the context of alkaloids reorganization. The semistability of the difluoromethylated ammonium salt, accessed by the reaction of tertiary amine and in situ generated difluorocarbene, enabled the attack at the α-position by various external nucleophiles. The utility and generality of the method is highlighted by its applications in the transformation of securinega, iboga, and sarpagine alkaloids to neosecurinega, chippiine/dippinine, and vobasine-type bisindole alkaloids, respectively. During the course of these biosynthetically inspired reorganizations, we could explore chemical reactivities of biogenetically relevant precursors.

Compact Measurement of the Optical Power in High-Power LED Using a Light-Absorbent Thermal Sensor.

LED (Light-Emitting Diode) presents advantages such as luminescence, reliability, durability compared with conventional lighting. It has been widely applied for life, healthcare, smart farm, industry, and lighting from indoor to the automotive headlamp. However, the LED is vulnerable to thermal damage originated from the high junction temperature, especially in high power applications. Hence, it requires precise qualification on the optical power and the junction temperature from the pilot line to secure reliability. In this study, the photo-thermal sensor is proposed by employing a sheet-type thermocouple composed of photo-absorbent metal film and thermocouple. This sensor aims low-cost qualification in pilot line for high-power luminous devices and optical monitoring of costly luminaire such as automobile LED headlamp. The sensor is designed to detect the increased temperature response of LED hot spots from the transferred thermal power and absorbed optical power. The temperature response of each sheet-type thermocouple is utilized as a signal output of the absorbed optical power and hot spot temperature based on the introduced sensor equation. The proposed thermal sensor is evaluated by comparing the experiment with the measured reference value from the integrating sphere and the attached thermocouple at a junction. The experiment result reveals 3% of the maximum error for the optical power of 645 mW.

Transition Metal-Catalyzed C-H Amination: Scope, Mechanism, and Applications.

Catalytic transformation of ubiquitous C-H bonds into valuable C-N bonds offers an efficient synthetic approach to construct N-functionalized molecules. Over the last few decades, transition metal catalysis has been repeatedly proven to be a powerful tool for the direct conversion of cheap hydrocarbons to synthetically versatile amino-containing compounds. This Review comprehensively highlights recent advances in intra- and intermolecular C-H amination reactions utilizing late transition metal-based catalysts. Initial discovery, mechanistic study, and additional applications were categorized on the basis of the mechanistic scaffolds and types of reactions. Reactivity and selectivity of novel systems are discussed in three sections, with each being defined by a proposed working mode.

Effects of aerobic and resistance exercise for 9 months on serum free light chains in type 2 diabetes.

Background and aims: Serum polyclonal free light chains (FLCs) levels are associated with overall survival in the general population, reflecting their utility as a biomarker of underlying immune activation and inflammation. Regular exercise is known to ameliorate low-grade inflammation in chronic diseases such as type 2 diabetes; however, the effects of different exercise training modalities on FLCs in adults with type 2 diabetes is unknown. This study investigated the effects of 9-month of aerobic, resistance or combined supervised exercise on serum FLCs in 164 patients with type 2 diabetes (age 58 ± 8 years; 63% female). Methods: 164 participants from the Health Benefits of Aerobic and Resistance Training in individuals with type 2 diabetes trial (HART-D) were randomly assigned to no exercise (n = 27), aerobic exercise alone (n = 41), resistance exercise alone (n = 49), or a combination of aerobic and resistance exercise (n = 47). Fasting serum samples were collected before and after completion of the intervention to quantify changes in kappa and lambda FLCs, and serum creatinine, using commercially-available ELISAs. Results: At baseline, combined kappa and lambda FLCs (FLC sum; calculated as kappa + lambda FLCs) were positively correlated with high-sensitive C-reactive protein (hs-CRP) (r = 0.237, p < 0.05) and fat mass (r = 0.162, p < 0.05), and negatively associated with aerobic fitness (r = -0.238, p < 0.05). While non-exercise controls exhibited an increase in FLCs over the 9-month study, exercise training blunted this increase (Δ FLC sum control arm: 3.25 ± 5.07 mg∙L-1 vs. all exercise arms: -0.252 ± 6.60 mg∙L-1, p < 0.05), regardless of exercise modality. Conclusion: Serum FLCs were associated with physical fitness and body composition in patients with type 2 diabetes. 9-month of exercise training prevented the accumulation of FLCs, regardless of exercise modality. Unlike hs-CRP-which did not change during the trial-serum FLCs may serve as a more sensitive biomarker of chronic low-grade inflammation in this population.

PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.

Proliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residues of PCNA in maintaining genomic integrity using in vitro, and cell-based assays and structural prediction. The predicted PCNAΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNAΔSL47 shows a defective interaction with PCNAWT leading to defects in homo-trimerization in vitro. PCNAΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNAΔSL47-expressing cells. Accordingly, PCNAΔSL47-expressing cells exhibit an increased number of single-stranded DNA gaps and higher levels of γH2AX, and sensitivity to DNA-damaging agents, highlighting the importance of PCNA Ser46-Leu47 residues in maintaining genomic integrity.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

BACKGROUND: Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. OBJECTIVES: To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. METHODS: The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. RESULTS: Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. CONCLUSION: A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system.

Dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells could play a role in predicting the response of asthmatics to treatment with corticosteroids.

BACKGROUND: Corticosteroids (CSs) are the preferred anti-inflammatory therapy for the treatment of asthma, but the responses of asthmatics to CSs are known to vary. It has thus become important to discover reliable markers in predicting responses to CSs. METHODS: We performed time-series microarrays using a murine model of asthma after a single dose of dexamethasone, based on the assumption that the gene showing a greater change in response to CSs can also be a potential marker for that finding. We then evaluated the clinical meaning of the gene discovered in the microarray experiments. RESULTS: We found that the expression of FK506 binding protein 51 gene (FKBP51) in lung tissue markedly increased after dexamethasone treatment in a murine model of asthma. We then measured dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells (PBMCs) in asthmatics. Dexamethasone-induced FKBP51 expression in PBMCs was significantly higher in severe asthmatics compared with mild-to-moderate asthmatics treated with inhaled CSs. In addition, we found that dexamethasone-induced FKBP51 expression in PBMCs was inversely correlated with improvement in lung function after treatment with orally administered prednisolone in six steroid-naive asthmatics. CONCLUSION: Dexamethasone-induced FKBP51 expression in PBMCs may be a reliable and practical biomarker in predicting the response to CSs in asthmatics.

Association between subcutaneous abdominal fat and airway hyperresponsiveness.

Epidemiological studies have shown that obesity is significantly associated with airway hyperresponsiveness (AHR). The aim of this study was to determine the effect of abdominal fat distribution on the prevalence of AHR. This study was conducted on subjects who visited the Seoul National University Hospital Gangnam Center from October 2003 to January 2009. Medical records of 3205 subjects who had both a methacholine bronchial provocation test and an abdominal CT scan were retrospectively reviewed. One hundred sixty-one subjects with AHR and their 161 controls were selected for the analysis. Total, subcutaneous, and visceral abdominal fat were objectively measured by an abdominal CT scan. Both body mass index (BMI) and waist circumference were significantly associated with AHR after adjustment for smoking (BMI: OR, 1.20; 95% confidence interval [CI], 1.07-1.35; waist circumference: OR, 1.07; 95% CI, 1.02-1.11). Total and subcutaneous abdominal fat increased the risk of AHR with an OR of 1.47 (95% CI, 1.08-2.02) in the case of total abdominal fat, and an OR of 1.99 (95% CI, 1.19-3.31) in the case of subcutaneous abdominal fat. However, visceral abdominal fat was not associated with AHR. The association between subcutaneous abdominal fat and AHR was consistent, especially in men. Subcutaneous abdominal fat was significantly associated with AHR, but visceral abdominal fat was not. These results suggest a possible role for subcutaneous fat on the later development of asthma.

Ir(III)-Catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling for the synthesis of N-H indoles.

Herein, an iridium(III)-catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling of unprotected 2-alkenyl anilines is described. The developed method allows the synthesis of a variety of 3-substituted N-H indole scaffolds under undivided electrolytic conditions. Mechanistic studies suggest that the reaction proceeds through the electro-oxidation induced reductive elimination pathway.

Toll-like receptor expression on peripheral blood mononuclear cells in asthmatics; implications for asthma management.

BACKGROUND: Accumulating evidence indicates that cells expressing Toll-like receptors (TLRs) play an important role in allergic diseases. The authors undertook this study to explore the hypothesis that TLR-mediated inflammatory signals are important from the perspective of asthma management. METHODS: The expressions of TLR1, TLR2, TLR3, TLR4, TLR6, and TLR9 and levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IFN-gamma) on the peripheral blood mononuclear cells (PBMCs) of 36 stable asthmatics on treatment (the on-treatment group), 15 asthmatics (the treatment-naïve group) before and after a 7-day course of oral prednisolone (30 mg/day), and on the PBMCs of 15 healthy controls were measured after in vitro stimulation using TLR-specific ligands. RESULTS: In the on-treatment group, TLR1, TLR2, TLR6, and TLR9 expressions on PBMCs were significantly different between asthmatics and controls. And the expression of TLR4 on PBMCs and TNF-alpha production stimulated by lipopolysaccharide (LPS), were significantly higher in mild to moderate than in severe asthmatics. Interestingly, in the treatment-naïve group, short-term prednisolone significantly increased LPS-induced TNF-alpha and IFN-gamma productions by PBMCs. CONCLUSION: TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.

Effectiveness of a computer-assisted asthma management program on physician adherence to guidelines.

BACKGROUND AND OBJECTIVE: Asthma is an example of a chronic disease for which there are evidence-based guidelines for primary care. The authors undertook this study to demonstrate that physicians' use and adherence to asthma management guidelines are improved when the guidelines are furnished in a computer-based format. METHODS: Based on established guidelines, the authors devised a practical and simple computer-assisted program focused on asthma treatment and monitoring. They then undertook a preliminary investigation, "Easy Asthma Management (EAM)" study, using this program. Finally, the authors evaluated the program's effectiveness by measuring clinical outcomes and changes in prescription patterns before and after the study. RESULTS: A total of 4682 asthma patients followed by 377 physicians were recruited, and 2187 completed the study (46.7%). The means of diurnal and nocturnal symptom scores were significantly reduced after a 3-month enrollment in the EAM study. Interestingly, the fraction of prescriptions for oral beta(2)-agonists, oral methylxanthines, and systemic steroids (oral or injection) significantly decreased after the EAM study (p = .02, p <.001, p <.001, respectively), whereas the fraction of prescriptions for inhaled forms of steroids combined with beta(2)-agonists increased significantly (p <.001). CONCLUSIONS: These findings suggest that a computer-assisted asthma management program can be used to improve the clinical outcomes of patients with asthma, and increase physician adherence to established guidelines.

Risk of hepatitis B virus reactivation in patients with asthma or chronic obstructive pulmonary disease treated with corticosteroids.

BACKGROUND AND OBJECTIVE: Reactivation of hepatitis B virus (HBV) is thought to be associated with immunosuppressive treatments, but insufficient information is available on the effect of corticosteroids. The aim of this study was to evaluate the risk of HBV reactivation in hepatitis B surface antigen-seropositive patients with asthma or COPD, who were treated with systemic corticosteroids (SCS) in addition to inhaled corticosteroids (ICS). METHODS: Patients with asthma or COPD (n = 198), who were hepatitis B surface antigen-seropositive and had been treated with ICS, were identified retrospectively. To evaluate the additional effects of SCS, the SCS group was divided into those who received intermittent or continuous SCS (≥3 months of continuous SCS treatment), and into those who received low-dose (≤20 mg/day of prednisolone) or medium-to-high-dose SCS. The study outcome was HBV reactivation. RESULTS: HBV reactivation occurred in 11.1% of patients in the SCS group, which was significantly higher than the reactivation rate in the ICS group. HBV reactivation was more frequent in the SCS group compared with the ICS group (OR 3.813, 95% CI: 1.106-13.145, P = 0.032), and in the continuous and medium-to-high-dose SCS subgroups compared with the ICS group (OR 5.719, 95% CI: 1.172-27.905, P = 0.048 and OR 4.884, 95% CI: 1.362-17.511, P = 0.014, respectively). CONCLUSIONS: These results suggest that addition of SCS to ICS increases the risk of HBV reactivation, especially when SCS are administered chronically or at high doses.

Customized Asthma Control Test with reflection on sociocultural differences.

We evaluated the utility and feasibility of customizing Asthma Control Test (ACT) items to generate a Korean Asthma Control Test (KACT) specific for Korean patients. We surveyed 392 asthma patients with 19 items, selected to reflect the Korean sociocultural context. Guideline ratings were integrated with the evaluations of specialists (i.e., using both guide base rating together with specialist's rating), and items with the greatest discriminating validity were identified. Stepwise regression methods were used to select items. KACT scale scores showed significant differences between the asthma control ratings generated by integrating ratings (r=0.77, P<0.001), by specialist's evaluations (r=0.54, P<0.001), or by FEV(1) percent predicted (r=0.39, P<0.001). Specialist's and guideline ratings detected 56% and 48.6% of patients with well-controlled asthma, respectively. However, the integrated ratings indicated that only 34.3% of the patients in the test sample were well controlled. The overall agreement between KACT and the integrated rating ranged from 45% to 78%, depending on the cut-off points used. It is possible to formulate a valid, useful country-specific diagnostic tool for the assessment of asthma patients based on the original ACT that reflect differences in sociocultural context.

Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer.

Chemical synthesis based on the skeletal variation has been prolifically utilized as an attractive approach for modification of molecular properties. Given the ubiquity of unstrained cyclic amines, the ability to directly alter such motifs would grant an efficient platform to access unique chemical space. Here, we report a highly efficient and practical strategy that enables the selective ring-opening functionalization of unstrained cyclic amines. The use of difluorocarbene leads to a wide variety of multifaceted acyclic architectures, which can be further diversified to a range of distinctive homologative cyclic scaffolds. The virtue of this deconstructive strategy is demonstrated by successful modification of several natural products and pharmaceutical analogues.

Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.

There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.

The effect of CpG-oligodeoxynucleotides with different backbone structures and 3' hexameric deoxyriboguanosine run conjugation on the treatment of asthma in mice.

CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3' hexameric deoxyriboguanosine-run (3' dG(6)-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3' dG(6)-run on asthma in presensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 microg) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG(6): CpG-ODN with 3' dG(6)-run, PE*-CpG-dG(6): PE-CpG-dG(6) with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG(6) only increased ovalbumin-specific IgG2a. PE*-CpG-dG(6) increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG(6) was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG(6)-run but also the modification of two PS linkages at 5' terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG(6) was less effective.

Epidemiology and current status of allergic rhinitis, asthma, and associated allergic diseases in Korea: ARIA Asia-Pacific workshop report.

The prevalence of allergic rhinitis and asthma has recently increased in Korea, and both conditions are recognized as major chronic respiratory diseases requiring active intervention. The prevalence of rhinitis among asthmatic patients is high, ranging from 60 to 80%, and could seriously affect asthma severity and outcome. We suggest that allergic rhinitis should be properly evaluated in asthmatic patients to achieve better asthma control.