Publications by authors named "Jong Eun Park"

150 Publications

Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine In Septic Shock: A Post-HOC Study of The Atess Trial.

Shock 2021 Sep 3. Epub 2021 Sep 3.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea Department of Emergency Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Statistics and Data Center, Samsung Medical Center, Seoul, Korea Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, Korea Department of Emergency Medicine, Guro Hospital, Korea University Medical Center, Seoul, Korea.

Introduction: We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock.

Methods: This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multi-center, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate.

Results: Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve.

Conclusion: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β.

Trial Registration: NCT, ClinicalTrials.gov NCT03756220, Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS). Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220.
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http://dx.doi.org/10.1097/SHK.0000000000001850DOI Listing
September 2021

Cardiac troponin I and the risk of cardiovascular or non-cardiovascular death in patients visiting the emergency department.

Sci Rep 2021 Aug 31;11(1):17461. Epub 2021 Aug 31.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

The prognostic implication of cardiac troponin I (cTnI) values for the determination of the magnitude or duration of cause-specific death risk is limited. We included consecutive patients with maximal cTnI values within 24 h of their emergency department visits. Multivariate analyses using variables selected by the Bayesian information criterion were performed to investigate the impact of cTnI on the event rate, time-dependent risk, and dose-dependent risk of cardiovascular or non-cardiovascular death within 360 days. There were 5472 (14.9%) all-cause deaths including 881 (2.4%) cardiovascular deaths and 4591 (12.5%) non-cardiovascular deaths. In patients with positive cTnI, defined as the ≥ 99th percentile of the upper normal limit, the cumulative risk of cardiac and non-cardiac death was 4.4- and 1.4-fold higher, respectively, than that of negative cTnI, respectively. In the competing risk analysis, positive cTnI was linked to 2.4- and 1.2-fold higher risks of cardiovascular and non-cardiovascular death, respectively. The cTnI value showed a positive relationship with the risk of both cardiovascular and non-cardiovascular deaths. In the time-dependent risk analysis, the excess risk of cardiovascular death was mostly evident in the first few weeks. Higher cTnI value was associated with an increased risk of both cardiovascular and non-cardiovascular death, especially which was in the early period.
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http://dx.doi.org/10.1038/s41598-021-96951-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408270PMC
August 2021

Molecular Characterization of Novel Family IV and VIII Esterases from a Compost Metagenomic Library.

Microorganisms 2021 Jul 29;9(8). Epub 2021 Jul 29.

Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

Two novel esterase genes, 8L and 13L, were isolated and identified from a compost metagenomic library. The encoded Est8L and Est13L had molecular masses of 33,181 and 44,913 Da consisting of 314 and 411 amino acids, respectively, without signal peptides. Est8L showed the highest identity (32.9%) to a hyper-thermophilic carboxylesterase AFEST from   compared to other esterases reported and was classified to be a novel member of family IV esterases with conserved regions such as HGGG, DY, GXSXG, DPL, and GXIH. Est13L showed the highest identity (98.5%) to the family VIII esterase Est7K from the metagenome library. Est8L and Est13L had the highest activities for -nitrophenyl butyrate (C4) and -nitrophenyl caproate (C6), respectively, and Est13L showed a broad substrate specificity for -nitrophenyl substrates. Est8L and Est13L effectively hydrolyzed glyceryl tributyrate. The optimum temperatures for activities of Est8L and Est13L were identical (40 °C), and the optimum pH values were 9.0 and 10.0, respectively. Est13L showed higher thermostability than Est8L. Sephacryl S-200 HR chromatography showed that the native form of Est8L was a dimer. Interestingly, Est13L was found to be a tetramer, contrary to other family VIII esterases reported. Est8L was inhibited by 30% isopropanol, methanol, and acetonitrile; however, Est13L was activated to 182.9% and 356.1%, respectively, by 30% isopropanol and methanol. Est8L showed enantioselectivity for the -form, but Est13L showed no enantioselectivity. These results show that intracellular Est8L and/or Est13L are oligomeric in terms of native forms and can be used for pharmaceutical and industrial applications with organic solvents under alkaline conditions.
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http://dx.doi.org/10.3390/microorganisms9081614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399190PMC
July 2021

Genome-Wide Association Study Identifies 12 Loci Associated with Body Weight at Age 8 Weeks in Korean Native Chickens.

Genes (Basel) 2021 Jul 29;12(8). Epub 2021 Jul 29.

Animal Genome & Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, Korea.

Meat from Korean native chickens (KNCs) has high consumer demand; however, slow growth performance and high variation in body weight (BW) of KNCs remain an issue. Genome-wide association study (GWAS) is a powerful method to identify quantitative trait-associated genomic loci. A GWAS, based on a large-scale KNC population, is needed to identify underlying genetic mechanisms related to its growth traits. To identify BW-associated genomic regions, we performed a GWAS using the chicken 60K single nucleotide polymorphism (SNP) panel for 1328 KNCs. BW was measured at 8 weeks of age, from 2018 to 2020. Twelve SNPs were associated with BW at the suggestive significance level ( < 2.95 × 10) and located near or within 11 candidate genes, including , , , , and . Gene set enrichment analysis based on the GWAS results at < 0.05 (1680 SNPs) showed that 32 Gene Ontology terms and two Kyoto Encyclopedia of Genes and Genomes pathways, including regulation of transcription, motor activity, the mitogen-activated protein kinase signaling pathway, and tight junction, were significantly enriched ( < 0.05) for BW-associated genes. These pathways are involved in cell growth and development, related to BW gain. The identified SNPs are potential biomarkers in KNC breeding.
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http://dx.doi.org/10.3390/genes12081170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394794PMC
July 2021

Transcriptomic Response under Heat Stress in Chickens Revealed the Regulation of Genes and Alteration of Metabolism to Maintain Homeostasis.

Animals (Basel) 2021 Jul 30;11(8). Epub 2021 Jul 30.

Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Wanju 55365, Korea.

Chicken is important livestock that serves as a vital food source which remain largely affected by heat stress. Therefore, we performed the transcriptome analysis to help understand the mechanisms of heat stress response in chickens. In the animal experiments, we grouped them into a normal and severe at 21 and 33 °C, with identified physiologic parameters for 2-weeks. Subsequently, RNA-seq analysis was performed to identify DEGs with a false discovery rate < 0.05 and a fold change ≥ 1.5. In the physiological parameters, we observed average daily gain was declined, rectal temperature and respiration rate was increased in severe group. Among total 245 DEGs, 230 and 15 genes were upregulated and downregulated, respectively. In upregulated DEGs, HSPs, and genes were identified as key genes in heat stress. The KEGG pathway analysis showed involvement in the ATP metabolic process, MAPK signaling pathway and calcium signaling pathway with related protein processing and synthesis. In conclusion, with induced heat stress, such changes in physiologic parameters alter the neuroendocrine system, and we observed that the heat stress environment regulates such Heat shock protein genes to protect the cells and proteins from an altered metabolism. These findings provide a more comprehensive understanding of the heat stress response in poultry.
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http://dx.doi.org/10.3390/ani11082241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388523PMC
July 2021

The effect of norepinephrine on common carotid artery blood flow in septic shock patients.

Sci Rep 2021 Aug 18;11(1):16763. Epub 2021 Aug 18.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 115 Irwon-ro, Gangnam-gu, Seoul, 06355, Republic of Korea.

This study was designed to evaluate the hemodynamic effect of norepinephrine (NE) on the peak systolic velocity (PSV), diameter, and blood flow of the common carotid artery (CCA) using the point-of-care ultrasound (POCUS) in patients with septic shock. The study involved patients above 18 years old with septic shock. Arterial monitoring, carotid ultrasonography, and transthoracic echocardiography were performed before NE administration (T). When the mean arterial pressure exceeded 65 mmHg after NE administration (T), the measurement was repeated. Twenty-four patients (median age 67 [interquartile range: 54-77] years; 42% female) with septic shock were examined in this study. Before (T) and after (T) NE administration, the PSV (mean, standard deviation [SD]) changed from 85.3 (21.1) cm/s to 83.5 (23.5) cm/s (p = 0.417); this change was not significant. However, the diameter and blood flow of the CCA increased significantly from 0.6 (0.09) cm and 0.75 (0.27) L/min to 0.66 (0.09) cm and 0.85 (0.27) L/min, respectively (p < 0.001). The diameter of the left ventricular outflow tract (LVOT) remained unchanged, but the velocity time integral of the LVOT increased significantly from 21.7 (4.39) cm to 23.6 (5.14) cm. There was no significant correlation between changes in blood flow of the CCA and changes in cardiac output (coefficient -0.365, p = 0.079). In conclusion, NE increased the diameter and blood flow of the CCA significantly, without changing the PSV in patients with septic shock.
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http://dx.doi.org/10.1038/s41598-021-96082-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373863PMC
August 2021

Prediction of Hanwoo Cattle Phenotypes from Genotypes Using Machine Learning Methods.

Animals (Basel) 2021 Jul 11;11(7). Epub 2021 Jul 11.

Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea.

Hanwoo was originally raised for draft purposes, but the increase in local demand for red meat turned that purpose into full-scale meat-type cattle rearing; it is now considered one of the most economically important species and a vital food source for Koreans. The application of genomic selection in Hanwoo breeding programs in recent years was expected to lead to higher genetic progress. However, better statistical methods that can improve the genomic prediction accuracy are required. Hence, this study aimed to compare the predictive performance of three machine learning methods, namely, random forest (RF), extreme gradient boosting method (XGB), and support vector machine (SVM), when predicting the carcass weight (CWT), marbling score (MS), backfat thickness (BFT) and eye muscle area (EMA). Phenotypic and genotypic data (53,866 SNPs) from 7324 commercial Hanwoo cattle that were slaughtered at the age of around 30 months were used. The results showed that the boosting method XGB showed the highest predictive correlation for CWT and MS, followed by GBLUP, SVM, and RF. Meanwhile, the best predictive correlation for BFT and EMA was delivered by GBLUP, followed by SVM, RF, and XGB. Although XGB presented the highest predictive correlations for some traits, we did not find an advantage of XGB or any machine learning methods over GBLUP according to the mean squared error of prediction. Thus, we still recommend the use of GBLUP in the prediction of genomic breeding values for carcass traits in Hanwoo cattle.
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http://dx.doi.org/10.3390/ani11072066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300336PMC
July 2021

Identification of de novo EP300 and PLAU variants in a patient with Rubinstein-Taybi syndrome-related arterial vasculopathy and skeletal anomaly.

Sci Rep 2021 Aug 5;11(1):15931. Epub 2021 Aug 5.

Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Rubinstein-Taybi syndrome (RSTS) is a human genetic disorder characterized by distinctive craniofacial features, broad thumbs and halluces, and intellectual disability. Mutations in the CREB binding protein (CREBBP) and E1A binding protein p300 (EP300) are the known causes of RSTS disease. EP300 regulates transcription via chromatin remodeling and plays an important role in cell proliferation and differentiation. Plasminogen activator, urokinase (PLAU) encodes a serine protease that converts plasminogen to plasmin and is involved in several biological processes such as the proteolysis of extracellular matrix-remodeling proteins and the promotion of vascular permeability and angiogenesis. Recently, we discovered a patient who presented with RSTS-related skeletal anomaly and peripheral arterial vasculopathy. To investigate the genetic cause of the disease, we performed trio whole genome sequencing of the genomic DNA from the proband and the proband's parents. We identified two de novo variants coined c.1760T>G (p.Leu587Arg) and c.664G>A (p.Ala222Thr) in EP300 and PLAU, respectively. Furthermore, functional loss of EP300a and PLAUb in zebrafish synergistically affected the intersegmental vessel formation and resulted in the vascular occlusion phenotype. Therefore, we hypothesize that the de novo EP300 variant may have caused RSTS, while both the identified EP300 and PLAU variants may have contributed to the patient's vascular phenotype.
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http://dx.doi.org/10.1038/s41598-021-95133-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342626PMC
August 2021

Respiratory Protection Effect of Ear-loop-type KF94 Masks according to the Wearing Method in COVID-19 Pandemic: a Randomized, Open-label Study.

J Korean Med Sci 2021 Jul 19;36(28):e209. Epub 2021 Jul 19.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Ear-loop-type Korean Filter 94 masks (KF94 masks, equivalent to the N95 and FFP2) are broadly used in health care settings in Korea for the coronavirus disease 2019 pandemic.

Methods: A prospective randomized open-label study was designed to identify differences in the fitting performance between mask wearing methods in three different types of KF94 mask with ear loops between January to March 2021. General-fitting involved wearing an ear-loop-type KF94 mask, and tight-fitting involved wearing a mask aided by a clip connecting the ear loops. Each of the 30 participants wore three types of masks according to a randomly assigned order in both methods and performed a total of six quantitative fit tests (QNFTs) according to the occupational safety and health administration protocol.

Results: All fit factors (FFs) measured by the QNFT were significantly higher for tight-fitting method with the clip in all KF94 masks ( < 0.001). However, the total FFs were very low, with a median (interquartile range) of 6 (3-23) and 29 (9-116) for general-fitting and tight-fitting, respectively. When wearing tightly, the horizontal 3-fold type mask with adjustable ear-loop length had the highest FF, with a median of 125, and the QNFT pass rate (FF ≥ 100) increased significantly from 4 (13%) to 18 (60%).

Conclusion: Even with sufficient filter efficiency, ear-loop-type-KF94 masks do not provide adequate protection. However, in relatively low-risk environments, wearing a face-seal adjustable KF94 mask and tight wearing with a clip can improve respiratory protection for healthcare workers.

Trial Registration: ClinicalTrials.gov Identifier: NCT04794556.
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http://dx.doi.org/10.3346/jkms.2021.36.e209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289716PMC
July 2021

Acetylcholinesterase and monoamine oxidase-B inhibitory activities by ellagic acid derivatives isolated from Castanopsis cuspidata var. sieboldii.

Sci Rep 2021 Jul 6;11(1):13953. Epub 2021 Jul 6.

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon, 57922, Republic of Korea.

Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4'-O-(α-L-rhamnopyranosyl)-3,3',4-tri-O-methylellagic acid (3) and 3,3',4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC values of 10.1 and 10.7 µM, respectively. Ellagic acid (5) inhibited AChE (IC = 41.7 µM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC = 7.27 µM) followed by 5 (IC = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (- 8.5 and - 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (- 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1038/s41598-021-93458-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260592PMC
July 2021

The Use of Point-of-care Ultrasound in Emergency Medical Centers in Korea: a National Cross-sectional Survey.

J Korean Med Sci 2021 May 31;36(21):e141. Epub 2021 May 31.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Point-of-care ultrasound (POCUS) is an essential tool in emergency medicine (EM). We aimed to investigate the current status and perception of POCUS use in emergency medical centers in Korea.

Methods: A cross-sectional, nationwide survey was conducted using a mobile survey of physicians at emergency medical centers in Korea. The first message was sent on November 27, 2020, and the second message was sent on December 3, 2020 to the non-responders. The questionnaire comprised 6 categories and 24 questionnaires on demographics, current practice, education, perception, and barriers to the use of POCUS.

Results: A total of 467 physicians participated in the survey (a response rate of 32% among 1,458 target physicians), of which 43% were residents and 57% were EM specialists. Most of the respondents (96%) answered that they use POCUS, of which 89% reported using it at least once a week. The most frequently used types of POCUS were focused assessment with sonography for trauma (68%) and echocardiography (66%). Musculoskeletal, male genital, and pediatric scans were rarely performed tests but ranked as of the scans physicians most wanted to learn. About 73% of the respondents received ultrasound education, and 41% received ultrasound education at their own institutions. Nevertheless, education-related barriers are still the biggest deterrent to POCUS use (60%). In addition, multivariate multinomial logistic regression analysis revealed that the greater the number of ultrasound devices and the total number of physicians in the emergency center, the more likely they were to use POCUS every day.

Conclusion: This study found that most physicians currently working in emergency medical centers in Korea more frequently perform various types of ultrasound scans compared to those 10 years prior. To further promote the use of POCUS, it is important to have an appropriate number of ultrasound devices and physicians in the emergency center along with systematic POCUS education.
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http://dx.doi.org/10.3346/jkms.2021.36.e141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167411PMC
May 2021

Prevalence of granular corneal dystrophy type 2-related p.R124H variant in a South Korean population.

Mol Vis 2021 8;27:283-287. Epub 2021 May 8.

GC Genome, Yongin, Korea.

Purpose: Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder and is associated with the arginine to histidine substitution at codon 124 (p.R124H) of the gene. Although p.R124H is known to be the most common corneal dystrophy-related pathogenic variant, there are few data on the frequency of this variant in the South Korean population.

Methods: In total, 2,060 anonymous DNA samples from a public umbilical cord blood bank were tested for the p.R124H variant using real-time PCR.

Results: Six of the 2,060 samples [0.29%; 95% confidence interval (CI), 0.12-0.67%] were heterozygous for the p.R124H variant. The prevalence of the GCD2-related p.R124H variant in this population was estimated to be 291.3 per 100,000 [95% confidence interval (CI), 118.5-667.0].

Conclusions: To our knowledge, this is the largest study that has estimated the prevalence of the GCD2-related p.R124H variant in South Korea.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116257PMC
May 2021

Erratum to: Mechanistic insight into the progressive retinal atrophy disease in dogs via pathway-based genome-wide association analysis.

J Anim Sci Technol 2021 Jan 31;63(1):198. Epub 2021 Jan 31.

Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea.

[This corrects the article DOI: 10.5187/jast.2020.62.6.765.].
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http://dx.doi.org/10.5187/jast.2021.63.1.198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882848PMC
January 2021

Mechanistic insight into the progressive retinal atrophy disease in dogs pathway-based genome-wide association analysis.

J Anim Sci Technol 2020 Nov 30;62(6):765-776. Epub 2020 Nov 30.

Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Korea.

The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case-control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at < 0.01 were extracted and mapped to 640 unique genes, and then selected significant ( < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.
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http://dx.doi.org/10.5187/jast.2020.62.6.765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721568PMC
November 2020

Exploring SERS from complex patterns fabricated by multi-exposure laser interference lithography.

Nanotechnology 2021 May 14;32(31). Epub 2021 May 14.

Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Designing uniform plasmonic surfaces in a large area is highly recommended for surface-enhanced Raman scattering (SERS). As periodic morphologies exhibit uniform SERS and optical tunability, diverse fabrication methods of periodic nanostructures have been reported for SERS applications. Laser interference lithography (LIL) is one of the most versatile tools since it can rapidly fabricate periodic patterns without the usage of photomasks. Here, we explore complex interference patterns for spatially uniform SERS sensors and its cost-effective fabrication method termed multi-exposure laser interference lithography (MELIL). MELIL can produce nearly periodic profiles along every direction confirmed by mathematical background, and in virtue of periodicity, we show that highly uniform Raman scattering (relative standard deviation <6%) can also be achievable in complex geometries as the conventional hole patterns. We quantitatively characterize the Raman enhancement of the MELIL complex patterns after two different metal deposition processes, Au e-beam evaporation and Ag electroplating, which results in 0.387 × 10and 1.451 × 10in enhancement factor respectively. This alternative, vacuum-free electroplating method realizes an even more cost-effective process with enhanced performance. We further conduct the optical simulation for MELIL complex patterns which exhibits the broadened and shifted absorption peaks. This result supports the potential of the expanded optical tunability of the suggested process.
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http://dx.doi.org/10.1088/1361-6528/abfb32DOI Listing
May 2021

Carrier frequency and incidence estimation of Smith-Lemli-Opitz syndrome in East Asian populations by Genome Aggregation Database (gnomAD) based analysis.

Orphanet J Rare Dis 2021 04 9;16(1):166. Epub 2021 Apr 9.

Green Cross Genome, 107, Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, 16924, Republic of Korea.

Background: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal, recessively inherited congenital malformation syndrome characterized by multiple congenital anomalies such as microcephaly with mental defects, distinctive facial features, genital abnormalities, and 2-3 syndactyly of the toes. SLOS is caused by defective 7-dehydrocholesterol reductase, which is encoded by the DHCR7 gene. This study aimed to analyze the carrier frequency and expected incidence of SLOS in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD) through the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline (2015 ACMG-AMP guideline).

Methods: We analyzed 9197 exomes for East Asian populations from gnomAD, comprising 1909 Korean, 76 Japanese, and 7212 other East Asian populations. All identified variants were classified according to the 2015 ACMG-AMP guideline.

Results: According to the 2015 ACMG-AMP guideline, 15 pathogenic variant/likely pathogenic variant (PV/LPV) cases were identified in 33 East Asian individuals (33/9191 = 0.4%). Among them, four PVs/LPVs were identified in 19 Korean individuals (19/1909 = 1.0%). The predicted incidence, based upon the carrier rates of PV/LPV of DHCR7 alleles, is 1 in 310,688 in East Asians and l in 40,380 in Koreans.

Conclusions: This study is the first to identify carrier frequencies in East Asians and Koreans using gnomAD. It was confirmed that East Asians (0.4%) had a lower carrier frequency than did other ethnicities (1-3%) and Koreans (1.0%) had similar or lower carrier frequencies than other ethnicities. The variant spectrums of DHCR7 in East Asian and Korean populations differed greatly from those of other ethnic groups.
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http://dx.doi.org/10.1186/s13023-021-01789-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033735PMC
April 2021

Impact of Personal Protective Equipment on the First-Pass Success of Endotracheal Intubation in the ED: A Propensity-Score-Matching Analysis.

J Clin Med 2021 Mar 4;10(5). Epub 2021 Mar 4.

Samsung Medical Center, Department of Emergency Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Various types and levels of personal protective equipment (PPE) are currently available to protect health-care workers against infectious diseases. However, wearing cumbersome PPE may negatively affect their performance in life-saving procedures. This study aimed to evaluate the impact of wearing extensive PPE, including a powered air-purifying respirator with a loose-fitting hood or an N95 filtering facepiece respirator, on the first-pass success (FPS) rate of endotracheal intubation (ETI) in the emergency department (ED). This study was a single-center, observational before-and-after study of 934 adult (≥18 years old) patients who underwent ETI in the academic ED. The study period was divided into a control period (from 20 January 2019, to 30 September 2019, and from 20 January 2018, to 30 September 2018) and an intervention period (from 20 January 2020, to 30 September 2020). Extensive PPE was not donned during the control period (control group, = 687) but was donned during the intervention period (PPE group, = 247). The primary outcome was the FPS rate. We used propensity score matching between the PPE and control groups to reduce potential confounding. Propensity score matching identified 247 cases in the PPE group and 492 cases in the control group. In the matched cohort, no significant difference was found in the FPS rate between the PPE and control groups (83.8% ( = 207) vs. 81.9% ( = 403); = 0.522). In multivariable analysis, wearing PPE was not associated with the FPS rate (adjusted odds ratio, 0.90; 95% confidence interval, 0.57-1.40; = 0.629) after adjusting for the level of the intubator (junior resident, senior resident, or emergency medicine (EM) specialist). In conclusion, the FPS rate is not significantly affected by wearing extensive PPE in the ED.
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http://dx.doi.org/10.3390/jcm10051060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961519PMC
March 2021

Single-Cell Toolkits Opening a New Era for Cell Engineering.

Mol Cells 2021 Mar;44(3):127-135

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

Since the introduction of RNA sequencing (RNA-seq) as a high-throughput mRNA expression analysis tool, this procedure has been increasingly implemented to identify cell-level transcriptome changes in a myriad of model systems. However, early methods processed cell samples in bulk, and therefore the unique transcriptomic patterns of individual cells would be lost due to data averaging. Nonetheless, the recent and continuous development of new single-cell RNA sequencing (scRNA-seq) toolkits has enabled researchers to compare transcriptomes at a single-cell resolution, thus facilitating the analysis of individual cellular features and a deeper understanding of cellular functions. Nonetheless, the rapid evolution of high throughput single-cell "omics" tools has created the need for effective hypothesis verification strategies. Particularly, this issue could be addressed by coupling cell engineering techniques with single-cell sequencing. This approach has been successfully employed to gain further insights into disease pathogenesis and the dynamics of differentiation trajectories. Therefore, this review will discuss the current status of cell engineering toolkits and their contributions to single-cell and genome-wide data collection and analyses.
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http://dx.doi.org/10.14348/molcells.2021.0002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019599PMC
March 2021

Integration of multi-omics approaches for functional characterization of muscle related selective sweep genes in Nanchukmacdon.

Sci Rep 2021 Mar 30;11(1):7219. Epub 2021 Mar 30.

Animal Genomics and Bioinformatics Division, National Institute of Animal Science, RDA, Wanju, 55365, Republic of Korea.

Pig as a food source serves daily dietary demand to a wide population around the world. Preference of meat depends on various factors with muscle play the central role. In this regards, selective breeding abled us to develop "Nanchukmacdon" a pig breeds with an enhanced variety of meat and high fertility rate. To identify genomic regions under selection we performed whole-genome resequencing, transcriptome, and whole-genome bisulfite sequencing from Nanchukmacdon muscles samples and used published data for three other breeds such as Landrace, Duroc, Jeju native pig and analyzed the functional characterization of candidate genes. In this study, we present a comprehensive approach to identify candidate genes by using multi-omics approaches. We performed two different methods XP-EHH, XP-CLR to identify traces of artificial selection for traits of economic importance. Moreover, RNAseq analysis was done to identify differentially expressed genes in the crossed breed population. Several genes (UGT8, ZGRF1, NDUFA10, EBF3, ELN, UBE2L6, NCALD, MELK, SERP2, GDPD5, and FHL2) were identified as selective sweep and differentially expressed in muscles related pathways. Furthermore, nucleotide diversity analysis revealed low genetic diversity in Nanchukmacdon for identified genes in comparison to related breeds and whole-genome bisulfite sequencing data shows the critical role of DNA methylation pattern in identified genes that leads to enhanced variety of meat. This work demonstrates a way to identify the molecular signature and lays a foundation for future genomic enabled pig breeding.
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http://dx.doi.org/10.1038/s41598-021-86683-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009959PMC
March 2021

Association between wide QRS pulseless electrical activity and hyperkalemia in cardiac arrest patients.

Am J Emerg Med 2021 07 18;45:86-91. Epub 2021 Feb 18.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Aim: We evaluated the relationship between hyperkalemia and wide QRS complex in patients with pulseless electrical activity (PEA) cardiac arrest.

Methods: This was a single-center, retrospective observational study of patients over the age of 18 treated for cardiac arrest at a tertiary referral hospital whose initial electrocardiogram rhythm was PEA from February 2010 to December 2019. Wide QRS PEA was defined as a QRS interval of 120 ms or more. Hyperkalemia was defined as serum potassium level > 5.5 mmol/L. The primary outcome was hyperkalemia. Multivariable logistic regression analysis was used to evaluate the relationship between wide QRS and hyperkalemia.

Results: Among 617 patients, we analyzed 111 episodes in the wide QRS group and 506 episodes in the narrow QRS group. The potassium level in the wide QRS group was significantly higher than in the narrow QRS group (5.4 mmol/L, IQR 4.4-6.7 vs. 4.6 mmol/L, IQR 4.0-5.6, P < 0.001). Among all patients, 49.6% (n = 55/111) in the wide QRS group had hyperkalemia, which was significantly higher than the 26.7% (n = 135/506) in the narrow QRS group (P < 0.001). In multivariable logistic regression analysis, wide QRS PEA was significantly associated with hyperkalemia (odds ratio = 2.86, 95% confidence interval: 1.80-4.53, P < 0.001).

Conclusions: Wide QRS PEA as an initial cardiac rhythm was significantly associated with hyperkalemia in cardiac arrest patients.
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http://dx.doi.org/10.1016/j.ajem.2021.02.024DOI Listing
July 2021

Genomic Analysis of Korean Patient With Microcephaly.

Front Genet 2020 28;11:543528. Epub 2021 Jan 28.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Microcephaly is a prevalent phenotype in patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in 40 Korean patients. We analyzed their clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and analysis of copy number variation (CNV). Infantile hypotonia and developmental delay were present in all patients. Thirty-four patients (85%) showed primary microcephaly. The diagnostic yield from the WES and CNV analyses was 47.5%. With WES, we detected pathogenic or likely pathogenic variants that were previously associated with microcephaly in 12 patients (30%); nine of these were variants with autosomal dominant inheritance. Two unrelated patients had mutations in the gene. In 10 other patients, we found mutations in the , and genes. Seven patients (17.5%) were diagnosed with pathogenic CNVs. Korean patients with microcephaly show a genetic spectrum that is different from that of patients with microcephaly of other ethnicities. WES along with CNV analysis represents an effective approach for diagnosis of the underlying causes of microcephaly.
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http://dx.doi.org/10.3389/fgene.2020.543528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876370PMC
January 2021

Prognostic implication of elevated cardiac troponin I in patients visiting emergency department without diagnosis of coronary artery disease.

Clin Chem Lab Med 2021 May 15;59(6):1107-1113. Epub 2021 Jan 15.

Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Objectives: Elevated cardiac troponin is not uncommon in patients visiting emergency department (ED) even without coronary artery disease, but its prognostic implication is not well understood in such patients.

Methods: In this retrospective single-center registry, we investigated clinical outcome of patients visiting ED without documented coronary artery disease. Patients were categorized according to the maximal value of Siemens ADVIA Centaur TnI-Ultra assay (TnI) within 24 h after visit. Primary endpoint was 180-day all-cause death that included cardiac and non-cardiac death.

Results: A total of 35,205 patients with median age 61 years and male gender 54.7% were included. Below the lowest level of detection (LOD) (≤0.006 ng/mL), between LOD and assay-specific <99th percentile (0.007-0.039 ng/mL), below median of ≥99th percentile (0.040-0.149 ng/mL), and above median of ≥99th percentile (≥0.150 ng/mL) TnI were found in 18,502 (52.6%), 11,338 (32.2%), 3,029 (8.6%), and 2,336 (6.6%) patients. In the 180-day follow-up period, 4,341 (12.3%) all-cause death including 694 (2.0%) cardiovascular death and 3,647 (10.4%) non-cardiovascular death developed. The risks of all-cause, cardiovascular, and non-cardiovascular death increased across higher TnI strata (hazard ratio [HR]=1.3 to 2.4; 2.0 to 9.3; 1.3 to 1.7; p<0.001, all). Analyses of multivariate models showed consistent results.

Conclusions: In patients visiting ED, elevated TnI was associated with higher risk of 180-day cardiovascular and non-cardiovascular death. Patients with elevated TnI may need additional evaluation or careful follow-up even without primary diagnosis of coronary artery disease.
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http://dx.doi.org/10.1515/cclm-2020-1392DOI Listing
May 2021

Genomic Prediction Based on SNP Functional Annotation Using Imputed Whole-Genome Sequence Data in Korean Hanwoo Cattle.

Front Genet 2020 21;11:603822. Epub 2021 Jan 21.

Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Wanju, South Korea.

Whole-genome sequence (WGS) data are increasingly being applied into genomic predictions, offering a higher predictive ability by including causal mutations or single-nucleotide polymorphisms (SNPs) putatively in strong linkage disequilibrium with causal mutations affecting the trait. This study aimed to improve the predictive performance of the customized Hanwoo 50 k SNP panel for four carcass traits in commercial Hanwoo population by adding highly predictive variants from sequence data. A total of 16,892 Hanwoo cattle with phenotypes (i.e., backfat thickness, carcass weight, longissimus muscle area, and marbling score), 50 k genotypes, and WGS imputed genotypes were used. We partitioned imputed WGS data according to functional annotation [intergenic (IGR), intron (ITR), regulatory (REG), synonymous (SYN), and non-synonymous (NSY)] to characterize the genomic regions that will deliver higher predictive power for the traits investigated. Animals were assigned into two groups, the discovery set (7324 animals) used for predictive variant detection and the cross-validation set for genomic prediction. Genome-wide association studies were performed by trait to every genomic region and entire WGS data for the pre-selection of variants. Each set of pre-selected SNPs with different density (1000, 3000, 5000, or 10,000) were added to the 50 k genotypes separately and the predictive performance of each set of genotypes was assessed using the genomic best linear unbiased prediction (GBLUP). Results showed that the predictive performance of the customized Hanwoo 50 k SNP panel can be improved by the addition of pre-selected variants from the WGS data, particularly 3000 variants from each trait, which is then sufficient to improve the prediction accuracy for all traits. When 12,000 pre-selected variants (3000 variants from each trait) were added to the 50 k genotypes, the prediction accuracies increased by 9.9, 9.2, 6.4, and 4.7% for backfat thickness, carcass weight, longissimus muscle area, and marbling score compared to the regular 50 k SNP panel, respectively. In terms of prediction bias, regression coefficients for all sets of genotypes in all traits were close to 1, indicating an unbiased prediction. The strategy used to select variants based on functional annotation did not show a clear advantage compared to using whole-genome. Nonetheless, such pre-selected SNPs from the IGR region gave the highest improvement in prediction accuracy among genomic regions and the values were close to those obtained using the WGS data for all traits. We concluded that additional gain in prediction accuracy when using pre-selected variants appears to be trait-dependent, and using WGS data remained more accurate compared to using a specific genomic region.
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http://dx.doi.org/10.3389/fgene.2020.603822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859490PMC
January 2021

Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus .

J Fungi (Basel) 2021 Jan 26;7(2). Epub 2021 Jan 26.

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as ) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC = 3.23 µM) compared to MAO-A (IC = 13.97 µM). HMC is a reversible competitive inhibitor with a K value of 0.896 µM. No cytotoxicity was observed in normal and cancer cells at 50 µM of HMC. HMC showed blood-brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (-7.3 kcal/mol) was higher than that of MAO-A (-6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 Å), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
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http://dx.doi.org/10.3390/jof7020084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911959PMC
January 2021

Recycling silver nanoparticle debris from laser ablation of silver nanowire in liquid media toward minimum material waste.

Sci Rep 2021 Jan 26;11(1):2262. Epub 2021 Jan 26.

Department of Mechanical Engineering, The State University of New York, Korea (SUNY Korea), 119 Songdo Moonhwa-ro, Yeonsu-gu, Incheon, 21985, Republic of Korea.

As silver nanowires (Ag NWs) are usually manufactured by chemical synthesis, a patterning process is needed to use them as functional devices. Pulsed laser ablation is a promising Ag NW patterning process because it is a simple and inexpensive procedure. However, this process has a disadvantage in that target materials are wasted owing to the subtractive nature of the process involving the removal of unnecessary materials, and large quantities of raw materials are required. In this study, we report a minimum-waste laser patterning process utilizing silver nanoparticle (Ag NP) debris obtained through laser ablation of Ag NWs in liquid media. Since the generated Ag NPs can be used for several applications, wastage of Ag NWs, which is inevitable in conventional laser patterning processes, is dramatically reduced. In addition, electrophoretic deposition of the recycled Ag NPs onto non-ablated Ag NWs allows easy fabrication of junction-enhanced Ag NWs from the deposited Ag NPs. The unique advantage of this method lies in using recycled Ag NPs as building materials, eliminating the additional cost of junction welding Ag NWs. These fabricated Ag NW substrates could be utilized as transparent heaters and stretchable TCEs, thereby validating the effectiveness of the proposed process.
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http://dx.doi.org/10.1038/s41598-021-81692-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838405PMC
January 2021

Developmental cell programs are co-opted in inflammatory skin disease.

Science 2021 01;371(6527)

Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London SE1 9RT, UK.

The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
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http://dx.doi.org/10.1126/science.aba6500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611557PMC
January 2021

Morpholine-based chalcones as dual-acting monoamine oxidase-B and acetylcholinesterase inhibitors: synthesis and biochemical investigations.

J Enzyme Inhib Med Chem 2021 Dec;36(1):188-197

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon, Republic of Korea.

Nine compounds () containing the morpholine moiety were assessed for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). Most of the compounds potently inhibited MAO-B; most potently inhibited with an IC value of 0.030 µM, followed by (0.25 µM). most potently inhibited AChE (IC = 6.1 µM), followed by (IC = 12.01 µM) and most potently inhibited MAO-A (IC = 7.1 µM). was a reversible mixed-type inhibitor of MAO-B ( = 0.018 µM); reversibly competitively inhibited AChE ( = 2.52 µM); and reversibly noncompetitively inhibited AChE ( = 7.04 µM). , and crossed the blood-brain barrier, and were non-toxic to normal VERO cells. These results show that is a selective inhibitor of MAO-B and that is a dual-acting inhibitor of AChE and MAO-B, and that both should be considered candidates for the treatment of Alzheimer's disease.
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http://dx.doi.org/10.1080/14756366.2020.1842390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808749PMC
December 2021

Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds.

Nat Commun 2020 12 11;11(1):6372. Epub 2020 Dec 11.

Epithelial Stem Cell Biology & Regenerative Medicine laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.
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http://dx.doi.org/10.1038/s41467-020-20082-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732825PMC
December 2020
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