Publications by authors named "Sanghun Lee"

130 Publications

Effects of Pig Skin Collagen Supplementation on Broiler Breast Meat.

Food Sci Anim Resour 2021 Jul 1;41(4):674-686. Epub 2021 Jul 1.

Department of Animal Science, Chungbuk National University, Cheongju 28644, Korea.

This study aimed to enhance the quality of broiler breast meat by adding pig skin collagen to feed. A total of 50 Ross 308 broilers were classified according to the following feeding regime for two weeks: basal diet (NC), basal diet+0.1% fish collagen (PC), basal diet+0.1% pig skin collagen (T1), basal diet+0.5% pig skin collagen (T2), and basal diet+1.0% pig skin collagen (T3). The moisture content was the highest in the PC group, and the protein content was the lowest in the T1 group (p<0.05). The fat content was higher in the T1 and PC groups, whereas the ash content was higher in the T3 group (p<0.05). Drip loss was the highest in the NC group and the lowest in the T2 group (p<0.05). Lightness was low in groups T2 and T3, redness was low in groups T2 and PC, and yellowness was low in groups T1, T2, and PC (p<0.05). The collagen content of the chicken breast was the highest in the T3 group, and that of the skin was the highest in the T1 group (p<0.05). The texture characteristics of springiness, cohesiveness, chewiness, and hardness were the highest in the T3 group (p<0.05). In conclusion, the supplementation of a broiler diet with pig skin collagen was found to increase the collagen content of the breast meat, indicating the improved quality of the broiler breast meat.
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http://dx.doi.org/10.5851/kosfa.2021.e28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277177PMC
July 2021

Local stability of cooperation in a continuous model of indirect reciprocity.

Sci Rep 2021 Jul 9;11(1):14225. Epub 2021 Jul 9.

Department of Physics, Pukyong National University, Busan, 48513, Korea.

Reputation is a powerful mechanism to enforce cooperation among unrelated individuals through indirect reciprocity, but it suffers from disagreement originating from private assessment, noise, and incomplete information. In this work, we investigate stability of cooperation in the donation game by regarding each player's reputation and behaviour as continuous variables. Through perturbative calculation, we derive a condition that a social norm should satisfy to give penalties to its close variants, provided that everyone initially cooperates with a good reputation, and this result is supported by numerical simulation. A crucial factor of the condition is whether a well-reputed player's donation to an ill-reputed co-player is appreciated by other members of the society, and the condition can be reduced to a threshold for the benefit-cost ratio of cooperation which depends on the reputational sensitivity to a donor's behaviour as well as on the behavioural sensitivity to a recipient's reputation. Our continuum formulation suggests how indirect reciprocity can work beyond the dichotomy between good and bad even in the presence of inhomogeneity, noise, and incomplete information.
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http://dx.doi.org/10.1038/s41598-021-93598-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270921PMC
July 2021

End-Tidal Carbon Dioxide Monitoring for Spontaneous Pneumothorax.

Emerg Med Int 2021 14;2021:9976543. Epub 2021 Jun 14.

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Background: Spontaneous pneumothorax should be classified as primary spontaneous pneumothorax (PSP) or secondary spontaneous pneumothorax (SSP) because treatment strategies may differ depending on underlying lung conditions and clinical course. The pulmonary dysfunction can lead to changes in end-tidal carbon dioxide (ETCO). The aim of this study was to investigate the difference in ETCO between PSP and SSP.

Methods: This retrospective observational study included adult patients diagnosed with spontaneous pneumothorax in the emergency room from April 2019 to September 2020. We divided patients into PSP and SSP groups and compared ETCO variables between the two groups.

Results: There were 33 (66%) patients in the PSP group and 17 (34%) patients in the SSP group. Initial ETCO was lower in the SSP group than in the PSP group (30 (23-33) vs. 35 (33-38) mmHg, =0.002). Multivariate analysis revealed that respiratory gas associated with SSP was initial ETCO (OR: 0.824; 95% CI: 0.697-0.974, =0.023). The optimal cutoff for initial ETCO to detection of SSP was 32 mmHg (area under curve, 0.754), with 76.5% sensitivity and 72.7% specificity.

Conclusion: ETCO monitoring is a reliable noninvasive indicator of differentiating between PSP and SSP. Initial ETCO lower than 32 mmHg is a predictor of SSP.
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http://dx.doi.org/10.1155/2021/9976543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216832PMC
June 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

Effect of Combined Bee Venom Acupuncture and NSAID Treatment for Non-Specific Chronic Neck Pain: A Randomized, Assessor-Blinded, Pilot Clinical Trial.

Toxins (Basel) 2021 06 23;13(7). Epub 2021 Jun 23.

Korean Medicine Life Science, Campus of Korea Institute of Oriental Medicine, University of Science & Technology (UST), Daejeon 34054, Korea.

This study aimed to investigate the feasibility of a combined treatment of bee venom acupuncture (BVA) and non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of non-specific chronic neck pain (NCNP). Patients with NCNP for ≥3 months were randomly allocated to a BVA, NSAIDs, or combined group (1:1:1), receiving 6 sessions of BVA, loxoprofen (180 mg daily), or a combination, respectively, for 3 weeks. Recruitment, adherence, and completion rates were calculated to assess feasibility. Bothersomeness, pain, disability, quality of life, depressive status, treatment credibility, and adverse events were assessed. In total, 60 participants were enrolled, and 54 completed the trial. Recruitment, adherence, and completion rates were 100%, 95%, and 90%, respectively. Bothersomeness, pain, disability, and depressive symptoms significantly improved in all groups after treatment ( < 0.05). The combined group showed continuous improvement during the follow-up period ( < 0.05). Quality of life was significantly improved ( < 0.05), and treatment credibility was maintained in the BVA and combined groups. No serious adverse events were reported. Combined treatment of BVA and NSAIDs are feasible for the treatment of NCNP, showing high persistence of the effect, credibility, and safety. Additional trials with longer follow-up are needed to confirm this effect.
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http://dx.doi.org/10.3390/toxins13070436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309931PMC
June 2021

Nonalcoholic Fatty Liver Disease for the Incidence of Drug-Induced Liver Injury.

Clin Gastroenterol Hepatol 2021 Jun 24. Epub 2021 Jun 24.

Department of Medical Consilience, Graduate School, Dankook University, Seoul, South Korea; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1016/j.cgh.2021.06.023DOI Listing
June 2021

Genome-wide association analysis of COVID-19 mortality risk in SARS-CoV-2 genomes identifies mutation in the SARS-CoV-2 spike protein that colocalizes with P.1 of the Brazilian strain.

Genet Epidemiol 2021 10 22;45(7):685-693. Epub 2021 Jun 22.

Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.

SARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Starting in October 2020, using the methodology of genome-wide association studies (GWAS), we looked at the association between whole-genome sequencing (WGS) data of the virus and COVID-19 mortality as a potential method of early identification of highly pathogenic strains to target for containment. Although continuously updating our analysis, in December 2020, we analyzed 7548 single-stranded SARS-CoV-2 genomes of COVID-19 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053 and 25,088 bp, achieved genome-wide significance (p values of 4.09e-09 and 4.41e-23, respectively), though only 25,088 bp remained significant in follow-up analyses. Our association findings were exclusively driven by the samples that were submitted from Brazil (p value of 4.90e-13 for 25,088 bp). The mutation frequency of 25,088 bp in the Brazilian samples on GISAID has rapidly increased from about 0.4 in October/December 2020 to 0.77 in March 2021. Although GWAS methodology is suitable for samples in which mutation frequencies varies between geographical regions, it cannot account for mutation frequencies that change rapidly overtime, rendering a GWAS follow-up analysis of the GISAID samples that have been submitted after December 2020 as invalid. The locus at 25,088 bp is located in the P.1 strain, which later (April 2021) became one of the distinguishing loci (precisely, substitution V1176F) of the Brazilian strain as defined by the Centers for Disease Control. Specifically, the mutations at 25,088 bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Since the mutations alter amino acid coding sequences, they potentially imposing structural changes that could enhance viral infectivity and symptom severity. Our analysis suggests that GWAS methodology can provide suitable analysis tools for the real-time detection of new more transmissible and pathogenic viral strains in databases such as GISAID, though new approaches are needed to accommodate rapidly changing mutation frequencies over time, in the presence of simultaneously changing case/control ratios. Improvements of the associated metadata/patient information in terms of quality and availability will also be important to fully utilize the potential of GWAS methodology in this field.
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http://dx.doi.org/10.1002/gepi.22421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426743PMC
October 2021

Harnessing the Physiological Functions of Cellular Prion Protein in the Kidneys: Applications for Treating Renal Diseases.

Biomolecules 2021 05 22;11(6). Epub 2021 May 22.

Stembio, Ltd., Entrepreneur 306, Soonchunhyang-ro 22, Sinchang-myeon, Asan 31538, Korea.

A cellular prion protein (PrP) is a ubiquitous cell surface glycoprotein, and its physiological functions have been receiving increased attention. Endogenous PrP is present in various kidney tissues and undergoes glomerular filtration. In prion diseases, abnormal prion proteins are found to accumulate in renal tissues and filtered into urine. Urinary prion protein could serve as a diagnostic biomarker. PrP plays a role in cellular signaling pathways, reno-protective effects, and kidney iron uptake. PrP signaling affects mitochondrial function via the ERK pathway and is affected by the regulatory influence of microRNAs, small molecules, and signaling proteins. Targeting PrP in acute and chronic kidney disease could help improve iron homeostasis, ameliorate damage from ischemia/reperfusion injury, and enhance the efficacy of mesenchymal stem/stromal cell or extracellular vesicle-based therapeutic strategies. PrP may also be under the influence of BMP/Smad signaling and affect the progression of TGF-β-related renal fibrosis. PrP conveys TNF-α resistance in some renal cancers, and therefore, the coadministration of anti-PrP antibodies improves chemotherapy. PrP can be used to design antibody-drug conjugates, aptamer-drug conjugates, and customized tissue inhibitors of metalloproteinases to suppress cancer. With preclinical studies demonstrating promising results, further research on PrP in the kidney may lead to innovative PrP-based therapeutic strategies for renal disease.
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http://dx.doi.org/10.3390/biom11060784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224798PMC
May 2021

Novel recessive locus for body mass index in childhood asthma.

Thorax 2021 Apr 22. Epub 2021 Apr 22.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Most genome-wide association studies of obesity and body mass index (BMI) have so far assumed an additive mode of inheritance in their analysis, although association testing supports a recessive effect for some of the established loci, for example, rs1421085 in In two whole-genome sequencing (WGS) studies of children with asthma and their parents (892 Costa Rican trios and 286 North American trios), we discovered an association between a locus (rs9292139) in and BMI that reaches genome-wide significance under a recessive model in the combined analysis. As the association does not achieve significance under an additive model, our finding illustrates the benefits of the recessive model in WGS analyses.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215742DOI Listing
April 2021

Transcriptome analysis of early stages of sorghum grain mold disease reveals defense regulators and metabolic pathways associated with resistance.

BMC Genomics 2021 Apr 22;22(1):295. Epub 2021 Apr 22.

Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN, 47907, USA.

Background: Sorghum grain mold is the most important disease of the crop. The disease results from simultaneous infection of the grain by multiple fungal species. Host responses to these fungi and the underlying molecular and cellular processes are poorly understood. To understand the genetic, molecular and biochemical components of grain mold resistance, transcriptome profiles of the developing grain of resistant and susceptible sorghum genotypes were studied.

Results: The developing kernels of grain mold resistant RTx2911 and susceptible RTx430 sorghum genotypes were inoculated with a mixture of fungal pathogens mimicking the species complexity of the disease under natural infestation. Global transcriptome changes corresponding to multiple molecular and cellular processes, and biological functions including defense, secondary metabolism, and flavonoid biosynthesis were observed with differential regulation in the two genotypes. Genes encoding pattern recognition receptors (PRRs), regulators of growth and defense homeostasis, antimicrobial peptides, pathogenesis-related proteins, zein seed storage proteins, and phytoalexins showed increased expression correlating with resistance. Notably, SbLYK5 gene encoding an orthologue of chitin PRR, defensin genes SbDFN7.1 and SbDFN7.2 exhibited higher expression in the resistant genotype. The SbDFN7.1 and SbDFN7.2 genes are tightly linked and transcribed in opposite orientation with a likely common bidirectional promoter. Interestingly, increased expression of JAZ and other transcriptional repressors were observed that suggested the tight regulation of plant defense and growth. The data suggest a pathogen inducible defense system in the developing grain of sorghum that involves the chitin PRR, MAPKs, key transcription factors, downstream components regulating immune gene expression and accumulation of defense molecules. We propose a model through which the biosynthesis of 3-deoxyanthocynidin phytoalexins, defensins, PR proteins, other antimicrobial peptides, and defense suppressing proteins are regulated by a pathogen inducible defense system in the developing grain.

Conclusions: The transcriptome data from a rarely studied tissue shed light into genetic, molecular, and biochemical components of disease resistance and suggested that the developing grain shares conserved immune response mechanisms but also components uniquely enriched in the grain. Resistance was associated with increased expression of genes encoding regulatory factors, novel grain specific antimicrobial peptides including defensins and storage proteins that are potential targets for crop improvement.
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http://dx.doi.org/10.1186/s12864-021-07609-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063297PMC
April 2021

Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells.

Integr Cancer Ther 2021 Jan-Dec;20:15347354211006191

Korea Basic Science Institute, Daejeon, Republic of Korea.

has been used as a traditional medicine in China and western countries for various diseases, including inflammation and cancer. However, the anti-cancer effect of chelidonine, a major compound of extracts, on pancreatic cancer remains poorly understood. In this study, we found that treatment with chelidonine inhibited proliferation of BxPC-3 and MIA PaCa-2 human pancreatic cancer cells. Annexin-V/propidium iodide staining assay showed that this growth inhibitory effect of chelidonine was induced through apoptosis. We found that chelidonine treatment upregulated mRNA levels and transcription factor activity in both cell lines. Increases in protein expression levels of p53, GADD45A, p21 and cleaved caspase-3 were also observed, with more distinct changes in MIA PaCa-2 cells compared to the BxPC-3 cells. These results suggest that chelidonine induces pancreatic cancer apoptosis through the p53 and GADD45A pathways. Our findings provide new insights into the use of chelidonine for the treatment of pancreatic cancer.
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http://dx.doi.org/10.1177/15347354211006191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077490PMC
April 2021

Multi-omics analyses implicate EARS2 in the pathogenesis of atopic dermatitis.

Allergy 2021 08 4;76(8):2602-2604. Epub 2021 Jun 4.

Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Korea.

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http://dx.doi.org/10.1111/all.14837DOI Listing
August 2021

Characteristics of injuries according to types of personal mobility devices in a multicenter emergency department from 2011 to 2017: A cross-sectional study.

Medicine (Baltimore) 2021 Feb;100(6):e24642

Department of Emergency Medicine, Hallym University College of Medicine, Dongtan Sacred Heart Hospital.

Abstract: Personal mobility devices (PMDs) have emerged as new factors in motor vehicle accidents, and related injuries are increasing. We aimed to describe the characteristics of PMD-related injuries presented to emergency departments (EDs) through a cross-sectional study for 7 years.This study is a multicenter cross-sectional study using the Emergency Department-based Injury In-Depth Surveillance database in South Korea. We identified all PMD-related injuries from 2011 to 2017 based on text searching. We categorized them into 3 groups based on their distinguishable characteristics: electric standing scooter (E-scooter), electric self-balancing wheel (E-wheel), and electronic board (E-board).A total of 448 PMD-related injuries were observed during the observation period. E-scooter-, E-wheel-, and E-board-related injuries occurred in 284, 138, and 26 cases, respectively. Most patients were between the ages of 19 and 59 years (69.2%), men (66.3%), and injured because of leisure activity (61.2%). The mechanism of injury was mostly traffic accidents (75.2%), but regarding injuries involving E-wheel and E-board, 25.4% and 30.8% of patients slipped from the device. The most commonly injured body part was the head, which accounted for 58.1% of E-scooter injuries, 38.4% of E-wheel injuries, and 53.9% of E-board injuries. Only 6 of all patients wore a helmet at the time of accident.PMD users and PMD-sharing programs are increasing, and more accidents are expected in the future. As PMDs are convenient to move and more people are willing to use them, proper riding and safety rules based on the type of PMD are needed to reduce the risk of injury. The results of this study can be used as basic data for developing safety policies.
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http://dx.doi.org/10.1097/MD.0000000000024642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886398PMC
February 2021

Community-level socioeconomic status and outcomes of patients with out-of-hospital cardiac arrest: A protocol for systematic review and meta analysis.

Medicine (Baltimore) 2021 01;100(3):e24170

National EMS Control Center, National Fire Agency, Sejong, Republic of Korea.

Background: The aim of this systematic review and meta-analysis was to investigate the associations of community-level socioeconomic status (SES) on outcomes of patients with out-of hospital cardiac arrest (OHCA).

Methods: A systematic literature review was conducted using PubMed, EMBASE, and the Cochrane database according to guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We included literature that presented the outcomes based on community-level SES among patients with OHCA. SES indicators included economic indicators such as income, wealth, and occupation, as well as combined indicators, where any of these indicators were integrated. Outcomes were bystander cardiopulmonary resuscitation (CPR) and survival to discharge.

Results: From 1394 titles, 10 cross-sectional observational studies fulfilled inclusion and exclusion criteria, representing 118,942 patients with OHCA. The odds ratios (ORs) of bystander CPR and survival to discharge for lower community-level SES patients were lower than those for higher community-level SES by economic SES indicators (bystander CPR OR 0.67; 95% CI 0.51-0.89, survival to discharge OR 0.60; 95% CI 0.35-1.02). Based on combined SES indicators the results showed similar patterns (bystander CPR OR 0.80; 95% CI 0.75-0.84, survival to discharge OR 0.76; 95% CI 0.63-0.92).

Conclusion: In this meta-analysis, community-level SES was significantly associated with bystander CPR and survival among patients with OHCA.
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http://dx.doi.org/10.1097/MD.0000000000024170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837968PMC
January 2021

The nationwide retrospective cohort study by Health Insurance Review and Assessment Service proves that asthma management decreases the exacerbation risk of asthma.

Sci Rep 2021 01 14;11(1):1442. Epub 2021 Jan 14.

Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea.

Medical costs have recently increased in South Korea due to the rising rate of asthma. Primary clinics serve an important role in asthma management, as they are the first stop for patients presenting with symptoms. The Health Insurance Review and Assessment Service (HIRA) in South Korea has assessed asthma-management quality since 2013, but studies are lacking on whether these assessments have been performed properly and contribute toward reducing asthma exacerbations. Therefore, we investigated whether the HIRA's quality assessments have decreased asthma exacerbations using national health insurance claims data from 2013 to 2017 of 83,375 primary-clinic and 15,931 tertiary-hospital patients with asthma. These patients were classified into four groups based on disease severity according to the monthly prescribed amount of asthma medication using K-means clustering. The associations between HIRA assessments and asthma exacerbation were analyzed using a generalized estimating equation. Our results showed that exacerbation odds gradually decreased as the HIRA assessments progressed, especially in the mild-severity group, and that exacerbation risk among patients with asthma decreased in the order of assessment grades: "Unsatisfactory," "Satisfactory," and "Tertiary." Therefore, we may conclude that asthma exacerbations may decrease with high quality asthma management; appropriate quality assessment could be helpful in reducing asthma exacerbations.
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http://dx.doi.org/10.1038/s41598-021-81022-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809363PMC
January 2021

Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus.

Genet Epidemiol 2021 04 8;45(3):316-323. Epub 2021 Jan 8.

Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.

Over 10,000 viral genome sequences of the SARS-CoV-2virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11,132 SARS-CoV-2 patients in the GISAID database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modeling the mutation rate, applying phylogenetic tree approaches, and so forth, we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index. Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. This is in line with a phylogenetic analysis which we use to contrast our results. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.
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http://dx.doi.org/10.1002/gepi.22373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005425PMC
April 2021

Causal Evaluation of Laboratory Markers in Type 2 Diabetes on Cancer and Vascular Diseases Using Various Mendelian Randomization Tools.

Front Genet 2020 21;11:597420. Epub 2020 Dec 21.

Department of Public Health Sciences, Seoul National University, Seoul, South Korea.

Multiple studies have demonstrated the effects of type 2 diabetes (T2D) on various human diseases; however, most of these were observational epidemiological studies that suffered from many potential biases including reported confounding and reverse causations. In this article, we investigated whether cancer and vascular disease can be affected by T2D-related traits, including fasting plasma glucose (FPG), 2-h postprandial glucose (2h-PG), and glycated hemoglobin A1c (HbA1c) levels, by using Mendelian randomization (MR). The summary statistics for FPG, 2h-PG, and HbA1c level were obtained through meta-analyses of large-scale genome-wide association studies that included data from 133,010 nondiabetic individuals from collaborating Meta-analysis of Glucose and Insulin Related Traits Consortium studies. Thereafter, based on the statistical assumptions for MR analyses, the most reliable approaches including inverse-variance-weighted (IVW), MR-Egger, MR-Egger with a simulation extrapolation (SIMEX), weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were applied to identify traits affected by FPG, 2h-PG, and HbAlc. We found that coronary artery disease is affected by FPG, as per the IVW [log odds ratio (logOR): 0.21; = 0.012], MR-Egger (SIMEX) (logOR: 0.22; = 0.014), MR-PRESSO (logOR: 0.18; = 0.045), and weighted median (logOR: 0.29; < 0.001) methods but not as per the MR-Egger (logOR: 0.13; = 0.426) approach. Furthermore, low-density lipoprotein cholesterol levels are affected by HbA1c, as per the IVW [beta (B): 0.23; = 0.015), MR-Egger (B: 0.45; = 0.046), MR-Egger (SIMEX) (B: 0.27; = 0.007), MR-PRESSO (B; 0.14; = 0.010), and the weighted median (B: 0.15; = 0.012] methods. Further studies of the associated biological mechanisms are required to validate and understand the disease-specific differences identified in the TD2-related causal effects of each trait.
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http://dx.doi.org/10.3389/fgene.2020.597420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780896PMC
December 2020

Synthesis and Photophysical Properties of a Series of Dimeric Indium Quinolinates.

Molecules 2020 Dec 23;26(1). Epub 2020 Dec 23.

Department of Chemistry Education, Chungbuk National University, Cheongju 28644, Korea.

A novel class of quinolinol-based dimeric indium complexes (-) was synthesized and characterized using H and C(H) NMR spectroscopy and elemental analysis. Compounds - exhibited typical low-energy absorption bands assignable to quinolinol-centered π-π* charge transfer (CT) transition. The emission spectra of - exhibited slight bathochromic shifts with increasing solvent polarity (-xylene < tetrahydrofuran (THF) < dichloromethane (DCM)). The emission bands also showed a gradual redshift, with an increase in the electron-donating effect of substituents at the C5 position of the quinoline groups. The absolute emission quantum yields (Φ) of compounds (11.2% in THF and 17.2% in film) and (17.8% in THF and 36.2% in film) with methyl substituents at the C5 position of the quinoline moieties were higher than those of the indium complexes with other substituents.
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http://dx.doi.org/10.3390/molecules26010034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793487PMC
December 2020

The Impact of Fibrin Sealant Volume on Skin Graft Contraction in a Full-Thickness Skin Graft Model.

J Craniofac Surg 2020 Nov/Dec;31(8):2156-2159

Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine.

Background: Fibrin sealant has been used for skin grafting in anatomically difficult facial areas. Although biodegradable, an excess of fibrin sealant may inhibit skin graft healing by inhibiting diffusion at the graft-recipient bed interface. The impact of fibrin sealant volume on graft healing was examined in a rat full-thickness skin graft model.

Methods: Seventy-two full-thickness 2.5 × 2.5-cm skin grafts were used on the dorsum of male Sprague-Dawley rats. The grafts were treated with three different volumes of fibrin sealant placed onto the recipient bed: 0.0 mL or normal saline (group 1), 0.1 mL (group 2), and 0.4 mL (group 3). Graft healing and complications were assessed using digital photographs and necropsies on postoperative days 3, 7, and 21.

Results: Group 3 showed the greatest graft contraction on days 3 and 21, while group 2 showed the least contraction on all 3 postoperative days (P = 0.002, 0.004, and <0.001, respectively). Histopathologic analysis showed inflammatory foreign body reactions in group 3 on days 3 and 7, and less vascular density on day 21 (P = 0.003). Group 1 showed the highest incidence of hematoma (P = 0.004).

Conclusion: An excess volume of fibrin sealant may produce pathologic wound contraction in skin grafting because a skin graft lacks a vascular pedicle and is highly dependent on diffusion from the host environment. Before using fibrin sealant for skin grafting in facial areas where the aesthetic outcome is important, the appropriate volume to use can be determined.
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http://dx.doi.org/10.1097/SCS.0000000000006629DOI Listing
March 2021

Cadmium phytoavailability from 1976 through 2016: Changes in soil amended with phosphate fertilizer and compost.

Sci Total Environ 2021 Mar 16;762:143132. Epub 2020 Oct 16.

Department of Life Science and Environmental Biochemistry, Pusan National University, Miryang 50463, South Korea; Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, South Korea. Electronic address:

This study aimed to determine cadmium (Cd) accumulation in arable soil, changes in Cd extractability and relevant soil properties, and Cd uptake by rice plants after long-term (50 years) application of phosphate (P) fertilizer and compost. A long-term field experiment was performed with rice crops from 1967 to 2016. Treatments included nitrogen and potassium fertilization (NK), nitrogen, phosphate, and potassium fertilization (NPK), nitrogen, phosphate, and potassium fertilization with compost application (NPK + compost), and control. Total Cd concentration in soil amended with NPK and NPK + compost continuously increased from 110 μg kg up to 232 μg kg from 1976 to 2016 but remained unchanged in control soil and soil amended with only NK. Plant-available Cd concentration in soil increased with year for all treatments, likely as a result of relevant changes in soil chemical properties. Cd concentrations in rice harvested in 2017 treated with NPK or NPK + compost were 212 μg Cd kg and 223 μg Cd kg, respectively. These values exceed the maximum permissible level (200 μg Cd kg) established by the Ministry of Food and Drug Safety of Korea.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143132DOI Listing
March 2021

Enhancing the Therapeutic Potential of 2-Overexpressing Mesenchymal Stem Cells in Acute Stroke.

Int J Mol Sci 2020 Oct 21;21(20). Epub 2020 Oct 21.

Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam 13488, Korea.

Although intravenous administration of mesenchymal stem cells (MSCs) is effective for experimental stroke, low engraftment and the limited functional capacity of transplanted cells are critical hurdles for clinical applications. C-C motif chemokine ligand 2 (CCL2) is associated with neurological repair after stroke and delivery of various cells into the brain via CCL2/CCR2 (CCL2 receptor) interaction. In this study, after CCL2-overexpressing human umbilical cord-derived MSCs (hUC-MSCs) were intravenously transplanted with mannitol in rats with middle cerebral arterial occlusion, we compared the differences between four different treatment groups: mannitol + CCL2-overexpressing hUC-MSCs (CCL2-MSC), mannitol + naïve hUC-MSCs (M-MSC), mannitol only, and control. At four-weeks post-transplantation, the CCL2-MSC group showed significantly better functional recovery and smaller stroke volume relative to the other groups. Additionally, we observed upregulated levels of CCR2 in acute ischemic brain and the increase of migrated stem cells into these areas in the CCL2-MSC group relative to the M-MSC. Moreover, the CCL2-MSC group displayed increased angiogenesis and endogenous neurogenesis, decreased neuro-inflammation but with increased healing-process inflammatory cells relative to other groups. These findings indicated that CCL2-overexpressing hUC-MSCs showed better functional recovery relative to naïve hUC-MSCs according to the increased migration of these cells into brain areas of higher CCR2 expression, thereby promoting subsequent endogenous brain repair.
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http://dx.doi.org/10.3390/ijms21207795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588958PMC
October 2020

Hydrogen bonding influences collision-induced dissociation of Na -bound guanine tetrads.

J Mass Spectrom 2020 May 30;56(4):e4582. Epub 2020 May 30.

Department of Chemistry, Gachon University, Seongnam-si, Republic of Korea.

Na -bound guanine (G)-tetrads possess square planar structures formed solely by noncovalent interactions including multiple hydrogen bonds. Unlike G-tetrads facilitated by other alkali metal ions, an intriguing behavior in collision-induced dissociation (CID) has been observed in Na -bound G-tetrads, which features a preferential, simultaneous loss of two G ligands in the low energy regime. To understand this unique behavior, we investigated the CID of Na -bound G-tetrads with mixed ligands of G and 9-methylguanine (9mG), [Na·G ·9mG ] (m + n = 4), and [Li·9mG ] for comparison. In the CID experiments, the simultaneous losses of two ligands were by far more pronounced than the loss of a single ligand for all five Na -bound G-tetrads. However, it appeared that the CID of [Li·9mG ] prefers to lose single ligands sequentially. An analysis of the fragment abundances suggested that the generation of Na -bound dimeric fragments might have occurred with two adjacent ligands. This theoretical study predicted for [Li·9mG ] that the loss of a single ligand is more energetically favorable than the production of neutral hydrogen-bonded fragments by 35.5 kJ/mol (ΔG). This contradicts our previous calculations for [Na·9mG ] that a neutral loss of hydrogen-bonded dimers provides the lowest energy product state of Na -bound dimeric fragments, which is lower than that of Na -bound trimeric fragments by 15.6 kJ/mol. From the results, this comparative study suggests that the pronounced generation of Na -bound dimeric fragments in CID of the G-tetrads is likely promoted by the dissociation pathway associated with neutral loss of hydrogen-bonded dimers. It thus demonstrates that multiple hydrogen bonding participating in formation of Na -bound G-tetrads may also strongly influence the fate of dissociating complexes of G-tetrads.
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http://dx.doi.org/10.1002/jms.4582DOI Listing
May 2020

Triterpenoids from the Leaves of Inhibit Ionizing Radiation-Induced Migration and Invasion of Human Lung Cancer Cells.

Evid Based Complement Alternat Med 2020 15;2020:3683460. Epub 2020 Sep 15.

Jeonju AgroBio-Materials Institute, Jeonju-si, Jeollabuk-do 54810, Republic of Korea.

Radiotherapy using ionizing radiation is a major therapeutic modality for advanced human lung cancers. However, ionizing radiation itself can induce malignant behaviors such as cancer cell migration and invasion, leading to local recurrence or distal metastasis. Therefore, safer and more effective agents that inhibit the metastatic behaviors of cancer cells in radiotherapy are needed. As a part of our ongoing search for new radiotherapy enhancers from medicinal herbs, we isolated the following triterpenoids from the ethanol extract of C: asiatic acid (1), madecassic acid (2), and asiaticoside (3). These compounds inhibited the ionizing radiation-induced migration and invasion of A549 human lung cancer cells at noncytotoxic concentrations. These results suggest that triterpenoids 1-3 isolated from . are candidate natural compounds to enhance the effect of radiotherapy in patients with non-small-cell lung cancer.
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http://dx.doi.org/10.1155/2020/3683460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532382PMC
September 2020

Anterior skull base reconstruction using nasoseptal flap: cadaveric feasibility study and clinical implication [SevEN-001].

J Otolaryngol Head Neck Surg 2020 Sep 21;49(1):67. Epub 2020 Sep 21.

Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine|, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03772, Republic of Korea.

Background: Pedicled nasoseptal flap (PNSF) has significantly improved the surgical outcomes of endoscopic endonasal approach (EEAs) by reducing cerebrospinal fluid (CSF) leakage. The purpose of this study is to assess the feasibility of using a PNSF for anterior skull base (ASB) reconstruction and to describe a method to compensate for a short flap based on our results.

Methods: In this cadaveric study, ASB dissection without sphenoidotomy was performed using 10 formalin-fixed and 5 fresh adult cadaver specimens, and the sufficiency of the PNSF to cover the ASB was assessed. After the sphenoidotomy, the length by which the PNSF fell short in providing coverage at the posterior wall of the frontal sinus (CPFS), and the extent of the anterior coverage from the limbus (CL) of the sphenoid bone was measured.

Results: Without sphenoidotomy, the mean length of the remaining PNSF after the coverage of the posterior wall of the frontal sinus was 0.67 cm. After sphenoidotomy, the PNSF fell short by a mean length of 2.10 cm, in providing CPFS. The CL was 1.86 cm. Based on these findings, defects resulting from an endoscopic resection of ASB tumors were reconstructed using PNSF without total sphenoidotomy in 3 patients. There were no postoperative CSF leaks or complications.

Conclusions: The use of PNSF for ASB reconstruction may be insufficient to cover the entire ASB defect after removal of large lesions which need total sphenoidotomy. When possible, by leaving some portion of the anterior sphenoid wall for supporting the PNSF, successful ASB reconstruction could be achieved in endoscopic resection of ASB tumors. Additional methods might be needed in some cases of large ASB lesions wherein the anterior sphenoid wall should be removed totally and the ASB defect is too large.
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http://dx.doi.org/10.1186/s40463-020-00460-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504836PMC
September 2020

Clinical Difference between Acute Appendicitis and Acute Right-Sided Colonic Diverticulitis.

Emerg Med Int 2020 1;2020:4947192. Epub 2020 Sep 1.

Department of Emergency Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.

Background: Clinical presentations of acute appendicitis (AA) and acute right-sided colonic diverticulitis (ARCD) are similar. However, the usual treatment for each disease differs between surgical and conservative management. The aim of this study was to identify clinical differences between AA and ARCD.

Method: We performed a single-center retrospective study on adult patients, with uncomplicated AA and ARCD confirmed by computed tomography, who visited an emergency department between March 2018 and August 2019. Clinical variables including past medical history, presented symptoms and signs, and laboratory findings were compared between the two groups. A logistic regression analysis was subsequently performed to differentiate ARCD from AA based on results of univariate analyses.

Results: A total of 212 (79.1%) and 56 (20.9%) patients were enrolled in AA and ARSD groups, respectively. Logistic regression analysis revealed that a past history of diverticulitis [OR: 102.679 (95% CI: 9.964-1058.055), < 0.001] was associated with ARCD, while ketonuria [OR: 2.907 (95% CI: 1.091-7.745), =0.033], anorexia [OR: 21.544 (95% CI: 3.905-118.868), < 0.001], and neutrophilia [OR: 3.406 (95% CI: 1.243-9.336), =0.017] were associated with AA.

Conclusion: Anorexia, neutrophilia, and ketonuria were predictors of AA while a history of diverticulitis was a predictor of ARCD.
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http://dx.doi.org/10.1155/2020/4947192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481953PMC
September 2020

An interaction of the 17q12-21 locus with mold exposure in childhood asthma.

Pediatr Allergy Immunol 2021 02 13;32(2):373-376. Epub 2020 Oct 13.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1111/pai.13376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277824PMC
February 2021

Acupuncture for dry eye syndrome after refractive surgery: A randomized controlled pilot trial.

Integr Med Res 2021 Mar 24;10(1):100456. Epub 2020 Jun 24.

Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.

Background: Dry eye syndrome is the most common complication of refractive surgery. Acupuncture is widely used for the treatment of ophthalmologic diseases, but to date, few have explored the effects of acupuncture for the treatment of this condition following refractive surgery. The objective of this study is to assess the feasibility of a study design for evaluating the effectiveness of acupuncture treatment along with usual care compared with usual care only for dry eye syndrome after refractive surgery.

Methods: A total of 18 patients with dry eye syndrome occurring after refractive surgery participated in this study. For 4 weeks, the acupuncture plus usual care and usual care only groups received treatment three times a week. A series of assessments, namely the ocular surface disease index (OSDI), visual analog scale for ocular discomfort, quality of life, tear film break-up time, Schirmer 1 test, and fluorescein-stained corneal-surface photography, along with other general assessments were carried out.

Results: Although preliminary, changes in OSDI from the baseline values were significantly different between the two groups at week 5 ( = 0.0003). There was a significant difference in the trends of OSDI changes between the acupuncture plus usual care and the usual care only groups ( = 0.0039). No serious adverse events were reported during the study.

Conclusion: Four weeks of acupuncture treatment in addition to usual care is a feasible treatment for dry eye syndrome after refractive surgery. A full-scale randomized controlled trial is needed to confirm the clinical effectiveness of acupuncture.
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http://dx.doi.org/10.1016/j.imr.2020.100456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452177PMC
March 2021

The safety and effectiveness of self-administered coffee enema: A systematic review of case reports.

Medicine (Baltimore) 2020 Sep;99(36):e21998

Korea Institute of Oriental Medicine, Yuseong-gu, Daejeon.

Background: As the self-administration of coffee enema is being used as a mean of self-care for detoxication in various indications, it is important that evidence-based public health information is provided for effective and safe use. However, the evidence is so far rare. This systematic review was conducted to investigate the safety and effectiveness of self-administered coffee enema in a wide range of use, and to provide evidence about its benefits and risks.

Methods: Relevant studies were retrieved from Ovid MEDLINE, Ovid Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature; and also from oriental databases, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, and Korea Institute of Science and Technology Information, Oriental Medicine Advanced Searching Integrated System, China National Knowledge Infrastructure, and Japan Science and Technology Information Aggregator. Considering self-administered coffee enema being used in a various indication, study population was not restricted. Any types of published studies that included outcomes of effectiveness and safety of self-administered coffee enema with or without comparators were eligible for this systematic review. Data on biomedical indications, patient-reported outcomes, and adverse events were collected. Descriptive analyses were planned because diverse health conditions and outcome variables did not allow for quantitative synthesis.

Results: Nine case reports that describe adverse events were identified and included in the analysis. Of these, 7 recent ones reported colitis after self-administration, mentioning that the most plausible cause assumed was the coffee fluid itself, which contained numerous chemical substances. Two others reported more critical adverse events. All 9 case reports with acceptable quality of evidence warned against the self-administration of the procedure. No study that reports the effectiveness of coffee enema was found.

Conclusions: Based on the evidences reviewed, this systematic review does not recommend coffee enema self-administration as a complementary and alternative medicine modality that can be adopted as a mean of self-care, given the unsolved issues on its safety and insufficient evidence with regard to the effectiveness.
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http://dx.doi.org/10.1097/MD.0000000000021998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478478PMC
September 2020

A novel locus for exertional dyspnoea in childhood asthma.

Eur Respir J 2021 02 4;57(2). Epub 2021 Feb 4.

Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Most children diagnosed with asthma have respiratory symptoms such as cough, dyspnoea and wheezing, which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated genetic susceptibility to asthma itself, but few have focused on important respiratory symptoms that characterise childhood asthma.Using whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnoea and exertional chest tightness. We tested whether genome-wide significant associations were replicated in two additional studies: 1) 286 asthmatic trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American current or former smokers from the COPDGene study.In the 894 Costa Rican trios, we identified a genome-wide significant association (p=2.16×10) between exertional dyspnoea and the single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3, that was replicated in the CAMP cohort (p=0.023) with the same direction of association (combined p=3.28×10). This association was not found in the African American participants from COPDGene. We also found suggestive evidence for an association between SNP rs10165869 and the atypical chemokine receptor 3 ().Our finding encourages the secondary association analysis of a wider range of phenotypes that characterise respiratory symptoms in other airway diseases/studies.
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http://dx.doi.org/10.1183/13993003.01224-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185954PMC
February 2021

Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation.

J Allergy Clin Immunol 2021 04 11;147(4):1453-1463. Epub 2020 Aug 11.

Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Seoul, Korea. Electronic address:

Background: The relationship between allergic and eosinophilic inflammation, either systemic or local, in allergic diseases remains unclear.

Objective: We performed combined genome-wide association study (GWAS) and epigenome-wide (EWAS) for atopy and tissue eosinophilia to identify both genetic and epigenetic signatures between systemic and local allergic inflammation, and to capture global patterns of gene regulation.

Methods: We included 126 subjects for atopy analysis and 147 for tissue eosinophilia analysis, as well as 18 normal nasal tissue samples. We identified differentially methylated positions (DMPs) and genes associated with atopy and tissue eosinophilia. Furthermore, we performed mendelian randomization analysis and penalized regression along with replication in an independent cohort.

Results: EWAS identified genes, including Musashi RNA binding protein 2 (MSI2), associated with atopy, which contained enriched DMPs that genetically affect atopy. A direct association was observed between MSI2 single-nucleotide polymorphisms and atopy, as was a causal effect of changes in MSI2 expression and methylation on atopy, which was replicated in a Costa Rican population. Regarding tissue eosinophilia, EWAS identified genes with enriched DMPs directly contributing to tissue eosinophilia at the gene level, including CAMK1D. The gene ontology terms of the identified genes for both phenotypes encompassed immune-related terms.

Conclusion: EWAS combined with GWAS identified novel candidate genes, especially the methylation of MSI2, contributing to systemic allergic inflammation. Certain genes displayed a greater association with either systemic or local allergic inflammation; however, it is expected that a harmonized effect of these genes influences immune responses.
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http://dx.doi.org/10.1016/j.jaci.2020.06.040DOI Listing
April 2021
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