Publications by authors named "Woo Jin Kim"

351 Publications

Patent landscape report on dental implants: A technical analysis.

Clin Implant Dent Relat Res 2021 Oct 20. Epub 2021 Oct 20.

Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, South Korea.

Background And Purpose: Significant research and development (R&D) has been conducted to make the best dental implants while developing various patent applications and registrations. In this study, we evaluated the current status of patents on dental implants and identified the future direction of R&D progress.

Materials And Methods: A total of 29 711 patents related to dental implants were reviewed. These were published between 1909 and 2020 and retrieved from the Derwent Innovation patent database. The patents were grouped into three categories depending on the implant components: fixture, abutment, and artificial teeth.

Results: The category with most patents was "abutment," and the most cited patent was "screw-type dental implant anchor." Global patenting trends over the past 20 years showed that both applicants and applications increased in the early 2010s; however, these have since been on the decline. Currently, the United States holds the largest number of patents, and Nobel Biocare Holding AG is the top assignee. Technic maturation prediction analysis showed that the current dental implant technology is in the "decline stage."

Conclusion: Trend analysis of the dental implant patent indicates the main contributors of development are profit-oriented companies. Recent reduction in the number of new patent applications suggests the technology is in the mature declining stage. The emergence of new materials or technologies that may close the gap in clinical unmet needs would reverse the trend.
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http://dx.doi.org/10.1111/cid.13048DOI Listing
October 2021

A multicenter study to identify the respiratory pathogens associated with exacerbation of chronic obstructive pulmonary disease in Korea.

Tuberc Respir Dis (Seoul) 2021 Oct 20. Epub 2021 Oct 20.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.

Background: Although respiratory tract infection is one of the most important trigger factors for acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), there are limited data on the epidemiologic patterns of microbiology in South Korea.

Methods: A multicenter observational study was conducted in 28 hospitals in South Korea between January 2015 and December 2018. Adult COPD patients with moderate to severe acute exacerbations were eligible for the present study. They underwent all conventional tests to identify etiologic microbiologic pathogens. The primary outcome was the percentage of different microbiological pathogens that caused AE-COPD. Comparative microbiological analysis was performed between the patients with asthma-COPD overlap (ACO) and pure COPD.

Results: We included 1,186 patients with AE-COPD. Pure COPD patients were 87.9% and ACO patients were 12.1%. Nearly half of the patients used an ICS-containing regimen and one-fifth used systemic corticosteroids. Among them, respiratory pathogens were found in 55.3%. Bacteria and viruses were found 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 found in ACO compared to pure COPD (8.3% vs 3.6%, p-value=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 for AE-COPD and become the basis for further research related with infectious pathogens in COPD patients.
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http://dx.doi.org/10.4046/trd.2021.0080DOI Listing
October 2021

Preclinical assessment of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells for neonatal hypoxic-ischaemic brain injury.

J Cell Mol Med 2021 Oct 15. Epub 2021 Oct 15.

Department of Toxicological Evaluation and Research, Korea Institute of Toxicology, Daejeon, Republic of Korea.

Hypoxic-ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin-preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin-preconditioned human Wharton's jelly-derived mesenchymal stem cells (th-hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th-hWJMSCs. MSCs were administered the maximum feasible dose (1 × 10 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th-hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague-Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th-hWJMSCs on the growth of newborn babies. Our results suggest that th-hWJMSCs are non-toxic and non-tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.
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http://dx.doi.org/10.1111/jcmm.16971DOI Listing
October 2021

Reduced receptor for advanced glycation end products is associated with α-SMA expression in patients with idiopathic pulmonary fibrosis and mice.

Lab Anim Res 2021 Oct 2;37(1):28. Epub 2021 Oct 2.

Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon, 24341, Republic of Korea.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Despite alveolar epithelial cells is crucial role in lung, its contribution and the associated biomarker remain unknown in the pathogenesis of IPF. Recently, environmental factors including stone dust, silica and cigarette smoking were found as risk factors involved in IPF. Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface receptors. It has been shown that interaction between RAGE and its ligands on immune cells mediates cellular migration and regulation of pro-inflammation. RAGE is highly expressed in the lung, in particular, alveolar epithelial cells. Therefore, we determined whether RAGE expression is associated with fibrosis-associated genes in patients with IPF and mice.

Results: When bleomycin (BLM) was intratracheally administered to C57BL/6 mice for 1, 2 weeks, macrophage and neutrophils were significantly increased. The fibrotic nodule formed and accumulation of collagen was determined after BLM injection in H&E- and Masson's trichrome staining. Levels of elastin, Col1a1 and fibronectin were increased in quantitative real-time PCR and protein levels of α-SMA was increased in western blot analysis. In the lung tissues of 1 mg/kg BLM-induced mice, RAGE expression was gradually decreased in 1- and 2 weeks in immunohistochemistry and western blot analysis, and 3 mg/kg of BLM-induced mice exhibited decreased RAGE levels while α-SMA expression was increased. We next determined RAGE expression in the lungs of IPF patients using immunohistochemistry. As a result, RAGE expression was decreased, while α-SMA expression was increased compared with non-IPF subjects.

Conclusions: Our findings suggest that reduced RAGE was associated with increased fibrotic genes in BLM-induced mice and patients with IPF. Therefore, RAGE could be applied with a biomarker for prognosis and diagnosis in the pathogenesis of IPF.
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http://dx.doi.org/10.1186/s42826-021-00105-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487524PMC
October 2021

Prevalence of depression and its associated factors in bronchiectasis: findings from KMBARC registry.

BMC Pulm Med 2021 Sep 27;21(1):306. Epub 2021 Sep 27.

Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, Korea.

Background: With the emergence of bronchiectasis as a common respiratory disease, epidemiological data have accumulated. However, the prevalence and impact of psychological comorbidities were not sufficiently evaluated. The present study examined the prevalence of depression and its associated factors in patients with bronchiectasis.

Methods: This study involved a multicenter cohort of bronchiectasis patients recruited from 33 pulmonary specialist hospitals. The baseline characteristics and bronchiectasis-related factors at enrollment were analyzed. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9).

Results: Of the 810 patients enrolled in the study, 168 (20.7%) patients had relevant depression (PHQ-9 score ≥ 10), and only 20 (11.9%) patients had a diagnosis of depression. Significant differences were noted in the depressive symptoms with disease severity, which was assessed using the Bronchiectasis Severity Index and E-FACED (all p < 0.001). Depressive symptoms inversely correlated with quality-of-life (r = - 0.704, p < 0.001) and positively correlated with fatigue severity score (r = 0.712, p < 0.001). Multivariate analysis showed that depression was significantly associated with the modified Medical Research Council dyspnea scale ≥ 2 (OR 2.960, 95% CI 1.907-4.588, p =  < 0.001) and high number of exacerbations (≥ 3) in the previous year (OR 1.596, 95% CI 1.012-2.482, p = 0.041).

Conclusions: Depression is common, but its association with bronchiectasis was underrecognized. It negatively affected quality-of-life and presented with fatigue symptoms. Among the bronchiectasis-related factors, dyspnea and exacerbation were closely associated with depression. Therefore, active screening for depression is necessary to optimize the treatment of bronchiectasis.

Trial Registration: The study was registered at Clinical Research Information Service (CRiS), Republic of Korea (KCT0003088). The date of registration was June 19th, 2018.
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http://dx.doi.org/10.1186/s12890-021-01675-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475377PMC
September 2021

DNA methylation changes associated with prenatal mercury exposure: A meta-analysis of prospective cohort studies from PACE consortium.

Environ Res 2021 Sep 22;204(Pt B):112093. Epub 2021 Sep 22.

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10, p-value = 5.87 × 10) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10) in GRK1 and cg02212000 (β = -0.001, p-value = 8.13 × 10) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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http://dx.doi.org/10.1016/j.envres.2021.112093DOI Listing
September 2021

Word Embedding Reveals Cyfra 21-1 as a Biomarker for Chronic Obstructive Pulmonary Disease.

J Korean Med Sci 2021 Sep 6;36(35):e224. Epub 2021 Sep 6.

Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.

Background: Although patients with chronic obstructive pulmonary disease (COPD) experience high morbidity and mortality worldwide, few biomarkers are available for COPD. Here, we analyzed potential biomarkers for the diagnosis of COPD by using word embedding.

Methods: To determine which biomarkers are likely to be associated with COPD, we selected respiratory disease-related biomarkers. Degrees of similarity between the 26 selected biomarkers and COPD were measured by word embedding. And we infer the similarity with COPD through the word embedding model trained in the large-capacity medical corpus, and search for biomarkers with high similarity among them. We used Word2Vec, Canonical Correlation Analysis, and Global Vector for word embedding. We evaluated the associations of selected biomarkers with COPD parameters in a cohort of patients with COPD.

Results: Cytokeratin 19 fragment (Cyfra 21-1) was selected because of its high similarity and its significant correlation with the COPD phenotype. Serum Cyfra 21-1 levels were determined in patients with COPD and controls (4.3 ± 5.9 vs. 3.9 ± 3.6 ng/mL, = 0.611). The emphysema index was significantly correlated with the serum Cyfra 21-1 level (correlation coefficient = 0.219, = 0.015).

Conclusion: Word embedding may be used for the discovery of biomarkers for COPD and Cyfra 21-1 may be used as a biomarker for emphysema. Additional studies are needed to validate Cyfra 21-1 as a biomarker for COPD.
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http://dx.doi.org/10.3346/jkms.2021.36.e224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422037PMC
September 2021

A genome-wide association study of quantitative computed tomographic emphysema in Korean populations.

Sci Rep 2021 08 17;11(1):16692. Epub 2021 Aug 17.

Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.
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http://dx.doi.org/10.1038/s41598-021-95887-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371078PMC
August 2021

Comparative analyses of the venom components in the salivary gland transcriptomes and saliva proteomes of some heteropteran insects.

Insect Sci 2021 Jul 23. Epub 2021 Jul 23.

Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Korea.

Salivary gland-specific transcriptomes of nine heteropteran insects with distinct feeding strategies (predaceous, hematophagous, and phytophagous) were analyzed and annotated to compare and identify the venom components as well as their expression profiles. The transcriptional abundance of venom genes was verified via quantitative real-time PCR. Hierarchical clustering of 30 representative differentially expressed venom genes from the nine heteropteran species revealed unique groups of salivary gland-specific genes depending on their feeding strategy. The commonly transcribed genes included a paralytic neurotoxin (arginine kinase), digestive enzymes (cathepsin and serine protease), an anti-inflammatory protein (cystatin), hexamerin, and an odorant binding protein. Both predaceous and hematophagous (bed bug) heteropteran species showed relatively higher transcription levels of genes encoding proteins involved in proteolysis and cytolysis, whereas phytophagous heteropterans exhibited little or no expression of these genes, but had a high expression of vitellogenin, a multifunctional allergen. Saliva proteomes from four representative species were also analyzed. All venom proteins identified via saliva proteome analysis were annotated using salivary gland transcriptome data. The proteomic expression profiles of venom proteins were in good agreement with the salivary gland-specific transcriptomic profiles. Our results indicate that profiling of the salivary gland transcriptome provides important information on the composition and evolutionary features of venoms depending on their feeding strategy.
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http://dx.doi.org/10.1111/1744-7917.12955DOI Listing
July 2021

A study on pyro-hydrometallurgical process for selective recovery of Pb, Sn and Sb from lead dross.

J Hazard Mater 2021 Sep 13;417:126071. Epub 2021 May 13.

Department of Energy and Resources Engineering, Chonnam National University, Gwangju, Republic of Korea. Electronic address:

This study is to propose a pyro-hydrometallurgical process for recovering Pb, Sn, and Sb from lead dross (LD), incorporating stages of roasting, leaching, and precipitation. The LD, containing 67.2% of Pb, 4.0% of Sn, and 1.4% of Sb, was first roasted at 750 °C for 2 h to oxidise the sulphide metals. Approximately 90% of Pb was oxidised from the first roasting. The LD was second roasted by mixing with 95% HSO for sulphatising at 300 °C for 3 h to break the complex oxide structure of the oxyplumboromeite (PbSbO). After the two-step roasting process, over 99% of Pb was oxidised and Sb was separated. The calcine obtained was desulphurised by 2 M NaCO solution for insoluble PbSO to PbCO for selective leaching. The residue was then leached in 2.5 M HNO at 50 °C for 3 h and over 99% of Pb dissolved into the solution while Sn and Sb remained in the solid residue. The Pb containing solution was neutralised at pH 8 using 2 M NaCO and over 99% Pb was precipitated as PbCO and Pb hydroxides. A residue containing Sn and Sb was leached in 7 M NaOH at 95 for 1 h and over 99% Sn was leached selectively. Sn in the solution was precipitated at pH 7 using 2 M HSO as SnO. Sb was recovered as SbO in solid reside from Sn leaching. The overall recovery rates of Pb, Sn, and Sb from the LD were 99.5%, 95.4%, and 86.3%, respectively. The proposed process is expected to contribute to recycling Pb and other metal values from LD by minimising hazardous waste emissions.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126071DOI Listing
September 2021

DNA Methylation Markers in Lung Cancer.

Curr Genomics 2021 Feb;22(2):79-87

Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea.

Lung cancer is the most common cancer and the leading cause of cancer-related morbidity and mortality worldwide. As early symptoms of lung cancer are minimal and non-specific, many patients are diagnosed at an advanced stage. Despite a concerted effort to diagnose lung cancer early, no biomarkers that can be used for lung cancer screening and prognosis prediction have been established so far. As global DNA demethylation and gene-specific promoter DNA methylation are present in lung cancer, DNA methylation biomarkers have become a major area of research as potential alternative diagnostic methods to detect lung cancer at an early stage. This review summarizes the emerging DNA methylation changes in lung cancer tumorigenesis, focusing on biomarkers for early detection and their potential clinical applications in lung cancer.
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http://dx.doi.org/10.2174/1389202921999201013164110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188581PMC
February 2021

A single amino acid variation of NV protein of viral hemorrhagic septicemia virus increases protein stability and decreases immune gene expression.

Fish Shellfish Immunol 2021 Sep 30;116:84-90. Epub 2021 Jun 30.

Department of Molecular Biology, Pusan National University, Busan, 46241, Republic of Korea. Electronic address:

Viral hemorrhagic septicemia virus (VHSV) causes severe mortality among more than 90 fish species. The 11 kb viral genome encodes six proteins including nonvirion protein (NV). In previous study, we reported that NV gene variations of VHSV decrease cellular energy metabolism. Among several NV mutant proteins, NV-S56L showed the highest cellular energy deprivation. Based on this finding, we further examined a molecular mechanism of one amino acid (S56L) change on differential cellular dysregulation. In the fish cells, the NV-S56L protein showed an increased level of cellular expression than normal and other mutant NV proteins without change of mRNA expression. Using cycloheximide treatment for exclude de novo NV protein expression, NV-S56L had an extensive half-life of intracellular protein. The proteasome inhibitor, MG-132, treatment recovered the all NV protein levels. The ubiquitination of NV was increased in the treatment of MG132 via inhibition of the ubiquitin/proteasome system process. Finally, increased protein stability of NV-S56L led to downregulation of NF-κB response immune gene expression. These results indicate that the prolonged protein stabilization of NV protein variant (NV-S56L) increases its pathological duration and might eventually lead to high virulence activity in the host fish cell.
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http://dx.doi.org/10.1016/j.fsi.2021.06.019DOI Listing
September 2021

Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics.

Allergy Asthma Immunol Res 2021 Jul;13(4):609-622

Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Although genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank.

Methods: Patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a value of < 5 × 10 was considered significant. We compared significant SNPs between Korean and UK patients with asthma.

Results: A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP ( = 4.5 × 10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (, IL1RL1, TSLP, and GATA3) and mucus plugging (, MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood.

Conclusions: The SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.
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http://dx.doi.org/10.4168/aair.2021.13.4.609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255356PMC
July 2021

Clinical outcomes in patients with lung cancer admitted to intensive care units.

Ann Transl Med 2021 May;9(10):836

Department of Internal Medicine, School of Medicine, Kangwon National University, Kangwon National University Hospital, Chuncheon, Republic of Korea.

Background: Recent advances in critical care and infection control have led to improved intensive care unit (ICU) survival rates. However, controversy exists regarding the benefits of ICU treatment for patients with lung cancer. In this study, we evaluated the clinical outcomes of patients from the Korean national database, who had been diagnosed with lung cancer and had received ICU treatment.

Methods: We investigated patients in Korea who had been newly diagnosed with lung cancer between January 1, 2008 and December 31, 2010. We classified these critically ill patients with lung cancer according to their lung cancer treatment pathways, with a specific focus on those who had undergone ICU treatment.

Results: We found that 31.3% of patients newly diagnosed with lung cancer had been admitted to the ICU for any reason, and 18.5% of patients with lung cancer were admitted to the ICU for reasons other than postoperative surgical lung cancer resection. The ICU mortality rate was 2.9% in patients admitted to the ICU for postoperative care and 47.5% in patients admitted for other reasons. Clinical cancer staging (HR, 7.02; 95% CI, 5.82-8.48; P<0.01) and the need for mechanical ventilator (HR, 1.34; 95% CI, 1.27-1.41; P<0.01) were independently associated with ICU mortality. The importance of mechanical ventilator intervention as a predictor for survival was significantly greater in the earlier stages of lung cancer (HR, 1.97; 95% CI, 1.15-3.38; P<0.01).

Conclusions: This study suggests that goals and treatment plans for critically ill patients with lung cancer should be determined by the individual patient's clinical cancer stage, regardless of the reason for admission to the ICU.
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http://dx.doi.org/10.21037/atm-21-298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184420PMC
May 2021

The Association with COPD Readmission Rate and Access to Medical Institutions in Elderly Patients.

Int J Chron Obstruct Pulmon Dis 2021 3;16:1599-1606. Epub 2021 Jun 3.

Department of Health Policy & Management, Kangwon National University, Chuncheon, South Korea.

Purpose: Up to 20% of patients with chronic obstructive pulmonary disease (COPD) require re-admission within 30 days of discharge after hospitalization for acute exacerbations of the disease. These re-admissions can increase morbidity and the economic burden of COPD. Reducing re-admissions has become a policy target in many developed countries. We investigated the risk factors for COPD re-admissions among older adults with COPD.

Patients And Methods: Data obtained from the National Health Insurance Service-Senior Cohort (NHIS-SC) in Korea were analyzed. The subjects included 558,147 patients aged ≥70 who had been admitted for COPD between 2013 and 2015. Re-admission was defined as being re-hospitalized within 30 days after discharge. The key variables selected from the database included income-based insurance contributions, demographical variables, information on inpatient medical services, types of healthcare facilities, and emergency time relevance index (TRI). The TRI is a regional medical-use analysis index that evaluates whether the capacity of the medical services available is appropriate for the medical needs of the target residents.

Results: In 814 COPD re-admission cases among 4867 total admissions due to COPD in elderly subjects, higher re-admission rates were associated with male sex, admission to district hospitals, medical aid recipients, and a longer hospital stay. When additionally adjusting the TRI to identify the difference in re-admission rates due to medical service accessibility, the same results were found, except for the areas of residence. The TRI was lower in re-admission cases (odds ratio 0.991 [95% CI, 0.984‒0.998], P = 0.013).

Conclusion: In this study, COPD re-admission rates among older adults were significantly associated with sex, length of hospital stay, and the type of hospital. The capacity of the medical services provided was also related to the COPD re-admission rate. Better access to appropriate emergency services is associated with reduction of COPD re-admission rates.
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http://dx.doi.org/10.2147/COPD.S302631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184368PMC
August 2021

Interactive Gene Expression Between JEF-290 and Longhorned Tick at Early Stage of Infection.

Front Physiol 2021 19;12:643389. Epub 2021 May 19.

Department of Agricultural Biology, College of Agriculture and Life Sciences, Jeonbuk National University, Jeonju, South Korea.

The longhorned tick, (Acari: Ixodidae), is a hard tick and a vector for severe fever with thrombocytopenia syndrome (SFTS) virus. The number of patients infected with SFTS is rapidly increasing. Recently, the invertebrate pathogen JEF-290 was reported to be useful to control the tick as an alternative to chemical acaricides, which are not easily applicable in human living areas where the tick is widely spread. In this study, we analyzed how the tick and the fungal pathogen interact at the transcriptional level. Field-collected tick nymphs were treated with JEF-290 conidia at 1 × 10 conidia/ml. In the early stage of infection with 2.5% mortality, the infected ticks were subjected to RNA sequencing, and non-infected ticks and fungal masses served as controls. Fungus and tick genes were mostly up-regulated at the early stage of infection. In the gene set enrichment analysis of the infecting fungus, catabolic processes that included lipids, phospholipids, and detoxification processes, the response to oxidative stress, and toxic substances were significantly up-regulated. In this fungal up-regulation, various lipase, antioxidant enzyme, and hydrolase genes were highly transcribed. The gene set enrichment analysis of the infected tick showed that many peptide synthesis processes including translation, peptide metabolism, ribonucleotide metabolism, and energy production processes that included ATP generation and ADP metabolism were significantly up-regulated. Structurally, mitochondria and ribosome subunit genes in ticks were highly transcribed to upregulate these processes. Together these results indicate that JEF-290 initiates process that infects the tick while the tick actively defends against the fungal attack. This work provides background to improve our understanding of the early stage of fungal infection in longhorned tick.
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http://dx.doi.org/10.3389/fphys.2021.643389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170561PMC
May 2021

Transcriptome Analysis of the Japanese Pine Sawyer Beetle, , Infected with the Entomopathogenic Fungus JEF-197.

J Fungi (Basel) 2021 May 10;7(5). Epub 2021 May 10.

Department of Agricultural Biology, College of Agriculture & Life Sciences, Jeonbuk National University, Jeonju 54896, Korea.

The Japanese pine sawyer (JPS) beetle, Hope (Coleoptera: Cerambycidae), damages pine trees and transmits the pine wilt nematode, Nickle. Chemical agents have been used to control JPS beetle, but due to various issues, efforts are being made to replace these chemical agents with entomopathogenic fungi. We investigated the expression of immune-related genes in JPS beetle in response to infection with JEF-197, a isolate, using RNA-seq. RNA samples were obtained from JEF-197, JPS adults treated with JEF-197, and non-treated JPS adults on the 8th day after fungal treatment, and RNA-seq was performed using Illumina sequencing. JPS beetle transcriptome was assembled and differentially expressed gene (DEG) analysis was performed. There were 719 and 1953 up- and downregulated unigenes upon JEF-197 infection, respectively. Upregulated contigs included genes involved in RNA transport, ribosome biogenesis in eukaryotes, spliceosome-related genes, and genes involved in immune-related signaling pathways such as the Toll and Imd pathways. Forty-two fungal DEGs related to energy and protein metabolism were upregulated, and genes involved in the stress response were also upregulated in the infected JPS beetles. Together, our results indicate that infection of JPS beetles by JEF-197 induces the expression of immune-related genes.
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http://dx.doi.org/10.3390/jof7050373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151162PMC
May 2021

Gene-disruption of the entomopathogenic fungus Beauveria bassiana incubated with dsRNA.

J Basic Microbiol 2021 Jul 13;61(7):642-651. Epub 2021 May 13.

Department of Agricultural Biology, Jeonbuk National University, Jeonju, Korea.

The species of Beauveria bassiana is widely used for the management of agricultural insect pests. In this study, we integrated egfp-double-stranded RNA (dsRNA) to a previously generated egfp-expressing B. bassiana transformant (Bb-egfp#3) using a protoplast integration method. The Bb-egfp#3 protoplast was mixed with the dsRNA under PEG/CaCl conditions and liquid-cultured in Sabouraud dextrose broth for 5 days. A control culture followed the same procedure without dsRNA. Bb-egfp#3/egfp-dsRNA cultures showed very low fungal growth (OD  = 0.2) compared to the control culture, Bb-egfp#3 only (OD  = 1.1). Screening of possible transformants on Sabouraud dextrose agar revealed a transformant T3, without egfp signal. T3 was confirmed as B. bassiana through sequencing of conserved genes and insect bioassays. Interestingly, the genomic egfp fragment of T3 was disrupted, and the egfp signal was not detected over four subcultures, which was also confirmed by RNA-seq of Bb-egfp#3 and T3. This study provides an interesting observation that protoplast integration with dsRNA could possibly generate significantly reduced gene expression in B. bassiana and it is stable across several generations.
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http://dx.doi.org/10.1002/jobm.202100049DOI Listing
July 2021

Correlation between Telomere Length and Chronic Obstructive Pulmonary Disease-Related Phenotypes: Results from the Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) Cohort.

Tuberc Respir Dis (Seoul) 2021 Jul 13;84(3):188-199. Epub 2021 May 13.

Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea.

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with increased prevalence in the elderly. Telomeres are repetitive DNA sequences found at the end of the chromosome, which progressively shorten as cells divide. Telomere length is known to be a molecular marker of aging. This study aimed to assess the relationship between telomere length and the risk of COPD, lung function, respiratory symptoms, and emphysema index in Chronic Obstructive Pulmonary Disease in Dusty Areas (CODA) cohort.

Methods: We extracted DNA from the peripheral blood samples of 446 participants, including 285 COPD patients and 161 control participants. We measured absolute telomere length using quantitative real-time polymerase chain reaction. All participants underwent spirometry and quantitative computed tomography scan. Questionnaires assessing respiratory symptoms and the COPD Assessment Test was filled by all the participants.

Results: The mean age of participants at the baseline visit was 72.5±7.1 years. Males accounted for 72% (321 participants) of the all participants. The mean telomere length was lower in the COPD group compared to the non-COPD group (COPD, 16.81±13.90 kb; non-COPD, 21.97±14.43 kb). In COPD patients, 112 (75.7%) were distributed as tertile 1 (shortest), 91 (61.1%) as tertile 2 and 82 (55%) as tertile 3 (longest). We did not find significant associations between telomere length and lung function, exacerbation, airway wall thickness, and emphysema index after adjusting for sex, age, and smoking status.

Conclusion: In this study, the relationship between various COPD phenotypes and telomere length was analyzed, but no significant statistical associations were shown.
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http://dx.doi.org/10.4046/trd.2021.0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273013PMC
July 2021

Association between long-term exposure to high levels of ambient air pollution and incidence of lung cancer in a population-based cohort.

Environ Res 2021 07 8;198:111214. Epub 2021 May 8.

Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi, 10408, Republic of Korea. Electronic address:

Although outdoor air pollution including particulate matter (PM) was classified as carcinogenic to humans based on accumulating epidemiological evidence, these findings were suggested mostly from low-dose environments in North America and Europe. We aimed to examine the association of long-term exposure to PM ≤ 10 and 2.5 μm in diameter (PM and PM) and nitrogen dioxide (NO) with lung cancer incidence using a population-based cohort in the Seoul Metropolitan Area (SMA), South Korea. Our study included 83,478 people residing in the SMA and followed up for 2007-2015 from the National Health Insurance Service-National Sample Cohort. This cohort was constructed based on the National Health Insurance database that contains sociodemographic and medical information under universal health coverage. Individual long-term concentrations of PM, PM, and NO were estimated at people's district-level and annually-updated residential addresses for the previous 5 years by using previously-validated prediction models. We applied a time-dependent Cox proportional hazards model and estimated hazard ratios (HRs) per 10 μg/m and 10 ppb increases in PM and NO, respectively, after adjusting for individual characteristics. During 9 years of follow-up, 489 lung cancer new cases occurred (714,012 person-year). The adjusted HRs for PM were greater than 1 but statistically non-significant (HR = 1.15; 95% CI = 0.88-1.52). We also did not find associations for PM and NO. Despite null associations for the total population, our subgroup analysis suggested associations with PM in family members with cancer (PM: HR = 2.59, 95% CI = 1.26-5.32; PM: 5.55, 1.09-27.91) and in those who have smoked more than 1 pack per day (1.77, 0.96-3.25; 3.81, 1.00-14.44) or for less than 20 years (2.81; 1.13-7.07; 2.02, 0.21-19.23). Our study based on a highly urbanized population exposed to relatively high air pollution provides no evidence of the association between PM and lung cancer incidence in the total population but indicates the potential susceptibility in heavy smokers for relatively short periods and family members of cancer patients. Future studies should re-examine the association using improved exposure assessment and extended population.
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http://dx.doi.org/10.1016/j.envres.2021.111214DOI Listing
July 2021

Validation of the Korean Version of the Anosognosia Questionnaire for Dementia.

Psychiatry Investig 2021 Apr 25;18(4):324-331. Epub 2021 Apr 25.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer's disease (AD) dementia.

Methods: We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated.

Results: Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI).

Conclusion: The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.
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http://dx.doi.org/10.30773/pi.2020.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103024PMC
April 2021

A systematic analysis of protein-altering exonic variants in chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2021 07 28;321(1):L130-L143. Epub 2021 Apr 28.

Department of Health Sciences, University of Leicester, Leicester, United Kingdom.

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant ( < 0.00015) when adjusting for lead GWAS single-nucleotide polymorphisms A common gasdermin B () splice variant (rs11078928) previously associated with a decreased risk for asthma was nominally associated with a decreased risk for COPD [minor allele frequency (MAF) = 0.46, = 1.8e-4]. Two stop variants in coiled-coil α-helical rod protein 1 (), a gene involved in regulating cell proliferation, were associated with COPD (both < 0.0001). The Z allele was associated with a random-effects odds ratio of 1.43 for COPD (95% confidence interval = 1.17-1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants and further define the role of coding variants in COPD pathogenesis.
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http://dx.doi.org/10.1152/ajplung.00009.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321852PMC
July 2021

Current advances of epigenetics in periodontology from ENCODE project: a review and future perspectives.

Clin Epigenetics 2021 04 26;13(1):92. Epub 2021 Apr 26.

Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Yeongeon-dong, Jongno-gu, Seoul, 03080, Korea.

Background: The Encyclopedia of DNA Elements (ENCODE) project has advanced our knowledge of the functional elements in the genome and epigenome. The aim of this article was to provide the comprehension about current research trends from ENCODE project and establish the link between epigenetics and periodontal diseases based on epigenome studies and seek the future direction.

Main Body: Global epigenome research projects have emphasized the importance of epigenetic research for understanding human health and disease, and current international consortia show an improved interest in the importance of oral health with systemic health. The epigenetic studies in dental field have been mainly conducted in periodontology and have focused on DNA methylation analysis. Advances in sequencing technology have broadened the target for epigenetic studies from specific genes to genome-wide analyses.

Conclusions: In line with global research trends, further extended and advanced epigenetic studies would provide crucial information for the realization of comprehensive dental medicine and expand the scope of ongoing large-scale research projects.
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http://dx.doi.org/10.1186/s13148-021-01074-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077755PMC
April 2021

Genotoxicity and subchronic general toxicity assessments of Lactobacillus curvatus WiKim 38 using Sprague-Dawley rats.

Food Chem Toxicol 2021 Jun 15;152:112199. Epub 2021 Apr 15.

Toxicologic Pathology Research Group, Korea Institute of Toxicology (KIT), 141 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea. Electronic address:

Lactobacillus curvatus WiKim 38 (LCW), isolated from kimchi, has shown novel immunomodulatory and anti-inflammatory properties. In the present study, to obtain data on the safety of LCW, we performed three genotoxicity (bacterial reverse mutation, chromosome aberration, and micronucleus) and two general toxicity (single-dosing and 13-week repeated-dosing) studies. In the genotoxicity assessment, LCW showed no increased reverse mutation for 4 strains of Salmonella typhimurium and a strain of Escherichia coli. In addition, LCW did not induce chromosome aberrations at concentrations up to 5000 μg/mL in cultured Chinese hamster lung (CHL) cells and did not induce an increased frequency of micronuclei in the bone marrow cells of rats at concentrations up to 2000 mg/kg. In the acute toxicity study using Sprague-Dawley (SD) rats, the approximate lethal dose of LCW was determined to be over 5000 mg/kg body weight (b.w.) in both sexes. Finally, in the subchronic toxicity study, no LCW-related adverse effects were observed at concentrations up to 5000 mg/kg b.w./day. Consequently, LCW is considered not to have mutagenic effects, and its no-observed-adverse-effect-level (NOAEL) is 5000 mg/kg b.w., equivalent to approximately 4.71 × 10 CFU/kg b.w., suggesting the LCW could be a potential probiotic for humans based on its safety profile.
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http://dx.doi.org/10.1016/j.fct.2021.112199DOI Listing
June 2021

Septal chondrocyte hypertrophy contributes to midface deformity in a mouse model of Apert syndrome.

Sci Rep 2021 04 12;11(1):7979. Epub 2021 Apr 12.

Department of Molecular Genetics and Dental Pharmacology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.

Midface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2 mutation (Col2a1-cre; Fgfr2) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. In Col2a1-cre; Fgfr2 mice, skull shape was normal at birth, but hypoplastic phenotypes became evident with age. General dimensional changes of mutant mice were comparable with those of mice with mutations in EIIa-cre; Fgfr2, a classic model of Apert syndrome in mice. Col2a1-cre; Fgfr2 mice showed some unique facial phenotypes, such as elevated nasion, abnormal fusion of the suture between the premaxilla and the vomer, and decreased perpendicular plate of the ethmoid bone volume, which are related to the development of the nasal septal cartilage. Morphological and histological examination revealed that the presence of increased septal chondrocyte hypertrophy and abnormal thickening of nasal septum is causally related to midface deformities in nasal septum-associated structures. Our results suggest that careful examination and surgical correction of the nasal septal cartilage may improve the prognosis in the surgical treatment of midface hypoplasia and respiratory problems in patients with Apert syndrome.
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http://dx.doi.org/10.1038/s41598-021-87260-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041873PMC
April 2021

Computed tomography-based visual assessment of chronic obstructive pulmonary disease: comparison with pulmonary function test and quantitative computed tomography.

J Thorac Dis 2021 Mar;13(3):1495-1506

Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.

Background: Chronic obstructive pulmonary disease (COPD) has variable subtypes involving mixture of large airway inflammation, small airway disease, and emphysema. This study evaluated the relationship between visually assessed computed tomography (CT) subtypes and clinical/imaging characteristics.

Methods: In total, 452 participants were enrolled in this study between 2012 and 2017. Seven subtypes were defined by visual evaluation of CT images using Fleischner Society classification: normal, paraseptal emphysema (PSE), bronchial disease, and centrilobular emphysema (trace, mild, moderate and confluent/advanced destructive). The differences in several variables, including clinical, laboratory, spirometric, and quantitative CT features among CT-based visual subtypes, were compared using the chi-square tests and one-way analysis of variance.

Results: Subjects who had PSE had better forced expiratory volume in 1 second (FEV1) (P=0.03) percentage and higher lung density (P<0.05) than those with moderate to confluent/advanced destructive centrilobular emphysema. As the visual grade of centrilobular emphysema worsened, pulmonary function declined and modified Medical Research Council, COPD assessment test (CAT) score, and quantitative assessment (emphysema index and air trapping) increased. The bronchial subtype was associated with higher body mass index (BMI), better lung function and higher lung density. Participants with trace emphysema showed a rapid increase in functional small airway disease.

Conclusions: Classifying subtypes using visual CT imaging features can reflect heterogeneity and pathological processes of COPD.
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http://dx.doi.org/10.21037/jtd-20-3041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024830PMC
March 2021

Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease.

Biomol Ther (Seoul) 2021 May;29(3):263-267

Department of Periodontology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Republic of Korea.

Periodontal disease is primarily associated with bacterial infection such as dental plaque. Dental plaque, an oral biofilm harboring a complex microbial community, can cause various inflammatory reactions in periodontal tissue. In many cases, the local bacterial invasion and host-mediated immune responses lead to severe alveolar bone destruction. To date, plaque control, non-surgical, and surgical interventions have been the conventional periodontal treatment modalities. Although adjuvant therapies including antibiotics or supplements have accompanied these procedures, their usage has been limited by antibiotic resistance, as well as their partial effectiveness. Therefore, new strategies are needed to control local inflammation in the periodontium and host immune responses. In recent years, target molecules that modulate microbial signaling mechanisms, host inflammatory substances, and bone immune responses have received considerable attention by researchers. In this review, we introduce three approaches that suggest a way forward for the development of new treatments for periodontal disease; (1) quorum quenching using quorum sensing inhibitors, (2) inflammasome targeting, and (3) use of FDA-approved anabolic agents, including Teriparatide and sclerostin antibody.
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http://dx.doi.org/10.4062/biomolther.2021.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094066PMC
May 2021

Human pluripotent stem-cell-derived alveolar organoids for modeling pulmonary fibrosis and drug testing.

Cell Death Discov 2021 Mar 15;7(1):48. Epub 2021 Mar 15.

Department of Internal Medicine, School of Medcine, Kangwon National University, Chuncheon, 24341, South Korea.

Detailed understanding of the pathogenesis and development of effective therapies for pulmonary fibrosis (PF) have been hampered by lack of in vitro human models that recapitulate disease pathophysiology. In this study, we generated alveolar organoids (AOs) derived from human pluripotent stem cells (hPSCs) for use as an PF model and for drug efficacy evaluation. Stepwise direct differentiation of hPSCs into alveolar epithelial cells by mimicking developmental cues in a temporally controlled manner was used to generate multicellular AOs. Derived AOs contained the expected spectrum of differentiated cells, including alveolar progenitors, type 1 and 2 alveolar epithelial cells and mesenchymal cells. Treatment with transforming growth factor (TGF-β1) induced fibrotic changes in AOs, offering a PF model for therapeutic evaluation of a structurally truncated form (NP-011) of milk fat globule-EGF factor 8 (MFG-E8) protein. The significant fibrogenic responses and collagen accumulation that were induced by treatment with TGF-β1 in these AOs were effectively ameliorated by treatment with NP-011 via suppression of extracellular signal-regulated kinase (ERK) signaling. Furthermore, administration of NP-011 reversed bleomycin-induced lung fibrosis in mice also via ERK signaling suppression and collagen reduction. This anti-fibrotic effect mirrored that following Pirfenidone and Nintedanib administration. Furthermore, NP-011 interacted with macrophages, which accelerated the collagen uptake for eliminating accumulated collagen in fibrotic lung tissues. This study provides a robust in vitro human organoid system for modeling PF and assessing anti-fibrotic mechanisms of potential drugs and suggests that modified MGF-E8 protein has therapeutic potential for treating PF.
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http://dx.doi.org/10.1038/s41420-021-00439-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961057PMC
March 2021

Surface Topography of Titanium Affects Their Osteogenic Potential through DNA Methylation.

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, 08826 Seoul, Korea.

It is widely accepted that sandblasted/large-grit/acid-etched (SLA) surfaces of titanium (Ti) have a higher osteogenic potential than machined ones. However, most studies focused on differential gene expression without elucidating the underlying mechanism for this difference. The aim of this study was to evaluate how the surface roughness of dental Ti implants affects their osteogenic potential. Mouse preosteoblast MC3T3-E1 cells were seeded on machined and SLA Ti discs. The cellular activities of the discs were analyzed using confocal laser scanning microscopy, proliferation assays, and real-time polymerase chain reaction (PCR). DNA methylation was evaluated using a methylation-specific PCR. The cell morphology was slightly different between the two types of surfaces. While cellular proliferation was slightly greater on the machined surfaces, the osteogenic response of the SLA surfaces was superior, and they showed increased alkaline phosphatase () activity and higher bone marker gene expression levels ( and ). The degree of DNA methylation on the gene was lower on the SLA surfaces than on the machined surfaces. DNA methyltransferase inhibitor stimulated the gene expression on the machined surfaces, similar to the SLA surfaces. The superior osteogenic potential of the SLA surfaces can be attributed to a different epigenetic landscape, specifically, the DNA methylation of genes. This finding offers novel insights into epigenetics to supplement genetics and raises the possibility of using epidrugs as potential therapeutic targets to enhance osteogenesis on implant surfaces.
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http://dx.doi.org/10.3390/ijms22052406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957554PMC
February 2021

Molecular Characterization of MAF1 and Its Potential Role as an Anti-Viral Hemorrhagic Septicaemia Virus Factor in Hirame Natural Embryo Cells.

Int J Mol Sci 2021 Jan 29;22(3). Epub 2021 Jan 29.

Biotechnology Research Division, National Institute of Fisheries Science, Busan 46083, Korea.

MAF1 is a global suppressor of RNA polymerase III-dependent transcription, and is conserved from yeast to human. Growing evidence supports the involvement of MAF1 in the immune response of mammals, but its biological functions in fish are unknown. We isolated and characterized from the olive flounder (). The coding region of comprised 738 bp encoding a 245-amino-acid protein. The deduced PoMAF1 amino acid sequence shared features with those of MAF1 orthologues from vertebrates. mRNA was detected in all tissues examined, and the levels were highest in eye and muscle tissue. The mRNA level increased during early development. In addition, the transcript level decreased during viral hemorrhagic septicemia virus (VHSV) infection of flounder hirame natural embryo (HINAE) cells. To investigate the role of in VHSV infection, single-cell-derived knockout HINAE cells were generated using the clustered regularly interspaced short palindromic repeats/CRISPR-associated-9 (CRISPR/Cas9) system, and cell clones with complete disruption of were selected. disruption increased the VHSV glycoprotein (G) mRNA levels during VHSV infection of HINAE cells, implicating PoMAF1 in the immune response to VSHV infection. To our knowledge, this is the first study to characterize fish , which may play a role in the response to viral infection.
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http://dx.doi.org/10.3390/ijms22031353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866426PMC
January 2021
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