Publications by authors named "Jung Eun Kim"

474 Publications

The influence of positive end-expiratory pressure (PEEP) in predicting fluid responsiveness in patients undergoing one-lung ventilation.

Int J Med Sci 2021 29;18(12):2589-2598. Epub 2021 Apr 29.

Department of Anesthesiology and Pain Medicine, Kangnam Sacred Heart Hospital, University of Hallym College of Medicine, Seoul, Korea.

Dynamic preload parameters such as pulse pressure variation (PPV) and stroke volume variation (SVV) have widely been used as accurate predictors for fluid responsiveness in patients under mechanical ventilation. To circumvent the limitation of decreased cyclic change of intrathoracic pressure, we performed an intermittent PEEP challenge test to evaluate whether PPV or SVV can predict fluid responsiveness during one-lung ventilation (OLV). Forty patients undergoing OLV were analyzed. Baseline hemodynamic variables including PPV and SVV and respiratory variables were recorded after chest opening in lateral position under OLV (T1). Five minutes after application of PEEP 10 cmHO, the parameters were recorded (T2). Thereafter, PEEP was withdrawn to 0 cmHO for 5 minutes (T3), and fluid loading was performed with balanced crystalloid solution 6 mL/kg of ideal body weight for 5 minutes. Five minutes after completion of fluid loading, all variables were recorded (T4). The patient was classified as fluid responder if SV increased ≥10% after fluid loading and as non-responder if SV increased <10%. Prediction of fluid responsiveness was evaluated with area under the receiver operating characteristic (ROC) curve (AUC). Change in stroke volume variation (ΔSVV) showed AUC of 0.9 (P < 0.001), 95% CI = 0.82-0.99, sensitivity = 88%, specificity = 82% for discrimination of fluid responsiveness. Change in pulse pressure variation (ΔPPV) showed AUC of 0.88 (P < 0.001), 95% CI = 0.78-0.97, sensitivity = 83%, specificity = 72% in predictability of fluid responsiveness. Cardiac index and stroke volume were well maintained after PEEP challenge in non-responders while they increased in responders. ΔPPV and ΔSVV induced by PEEP challenge are reliable parameters to predict fluid responsiveness as well as very good predictors of fluid unresponsiveness during OLV.
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http://dx.doi.org/10.7150/ijms.59653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176162PMC
April 2021

Acupuncture combined with multidisciplinary care for recovery after traumatic multiple rib fractures: a prospective feasibility cohort study.

Acupunct Med 2021 May 28:9645284211009539. Epub 2021 May 28.

Department of Nursing, Pusan National University Hospital, Busan, South Korea.

Introduction: Acute pain significantly delays early physiological recovery and results in chronic functional disability in patients with traumatic multiple rib fractures (MRFs). This prospective cohort study aimed to investigate the feasibility of acupuncture combined with multidisciplinary care during recovery in patients with traumatic MRFs.

Methods: Twenty patients with traumatic MRFs who were admitted to a regional trauma centre in South Korea were enrolled. A combination of acupuncture and multidisciplinary inpatient ward management was provided at the trauma ward. Patients were permitted to continue acupuncture treatments at outpatient clinics for 3 months after the traumatic events. Clinical outcomes, including pain, acute physiological recovery, quality of life, patient satisfaction with the care provided, respiratory function and use of opioids, were evaluated up to 6 months after trauma.

Results: Seventeen (85%) participants completed the 6-month follow-up. One patient withdrew consent during admission due to discomfort after three sessions of acupuncture. The proportion of patients with above-moderate level of pain decreased from 95% at baseline to 41% at 6 months. Quality of life appeared to deteriorate consistently throughout the study period. Around 80% of respondents expressed satisfaction with the acupuncture treatments and stated that they found acupuncture to be acceptable. Over 94% of respondents reported slight or considerable improvement.

Conclusion: The provision of acupuncture combined with multidisciplinary care for recovery in patients with traumatic MRFs was feasible in a regional trauma centre in South Korea. Randomised trials are needed to investigate the role of acupuncture combined with multidisciplinary care in the future.

Trial Registration Number: KCT0002911 (Clinical Research Information Service).
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http://dx.doi.org/10.1177/09645284211009539DOI Listing
May 2021

Enhancing the cardiovascular protective effects of a healthy dietary pattern with wolfberry (Lycium barbarum): A randomized controlled trial.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore, Singapore.

Background: The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits.

Objectives: To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore.

Methods: This is a 16-week, parallel design, randomized controlled trial. All participants (n = 40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid-lipoproteins and blood pressure were evaluated every 4 weeks.

Results: All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92 ± 1.73 nmol/mL; control: 5.01 ± 2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19 ± 0.06 pg/mL; control: -0.15 ± 0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08 ± 0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8 ± 0.5%) and vascular age (-1.9 ± 1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes.

Conclusions: In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid-lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844.
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http://dx.doi.org/10.1093/ajcn/nqab062DOI Listing
May 2021

Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years.

Viruses 2021 04 30;13(5). Epub 2021 Apr 30.

HIV Databases, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and . In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in and genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.
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http://dx.doi.org/10.3390/v13050806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145643PMC
April 2021

The impact of tryptophan supplementation on sleep quality: a systematic review, meta-analysis, and meta-regression.

Nutr Rev 2021 May 3. Epub 2021 May 3.

C.N. Sutanto, W.W. Loh, and J.E. Kim are with Department of Food Science and Technology, Faculty of Science, National University of Singapore, Singapore.

Context: L-tryptophan (Trp) has been documented to aid sleep, but a systematic compilation of its effect on sleep quality is still limited.

Objective: We assessed the effect of Trp supplementation on sleep quality via meta-analysis and meta-regression. The effects of daily Trp dose (<1 g and ≥1 g) were also assessed.

Data Sources: A database search was done in PubMed, Medline (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Cochrane and a total of 18 articles were collected.

Data Extraction: Extracted data from 4 articles were also analyzed using random-effect meta-analysis and meta-regression. Standardized mean difference (SMD) was used in meta-analysis.

Data Analysis: Results from the study suggested that Trp supplementation can shorten wake after sleep onset (-81.03 min/g, P = 0.017; SMD, -1.08 min [95%CI, -1.89 to -0.28]). In addition, the group receiving ≥1 g Trp supplementation had a shorter wake after sleep onset than the group with Trp < 1g supplementation (Trp <1 g vs Trp ≥1 g: 56.55 vs 28.91 min; P = 0.001). However, Trp supplementation did not affect other sleep components.

Conclusion: Trp supplementation, especially at ≥1 g can help improve sleep quality.
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http://dx.doi.org/10.1093/nutrit/nuab027DOI Listing
May 2021

Aryl Hydrocarbon Receptor and Autophagy-Related Protein Microtubule-Associated Protein Light Chain 3 Expression in Psoriasis.

Ann Dermatol 2021 Apr 8;33(2):138-146. Epub 2021 Mar 8.

Department of Dermatology, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea.

Background: The aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis. However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown.

Objective: We studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them.

Methods: We included 24 psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. , , , , and mRNA levels were measured by quantitative polymerase chain reaction.

Results: AHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls.

Conclusion: AHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases.
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http://dx.doi.org/10.5021/ad.2021.33.2.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082009PMC
April 2021

Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

Int J Mol Sci 2021 Apr 27;22(9). Epub 2021 Apr 27.

Department of Dermatology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea.

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/β-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1β, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/β-catenin signaling pathway, such as in the Wnt families, β-catenin, phosphorylated GSK-3β and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/β-catenin and JAK/STAT pathways in hORSCs.
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http://dx.doi.org/10.3390/ijms22094581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123883PMC
April 2021

Vaccination Prioritization Strategies for COVID-19 in Korea: A Mathematical Modeling Approach.

Int J Environ Res Public Health 2021 04 16;18(8). Epub 2021 Apr 16.

Department of Mathematical Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.

Coronavirus disease 2019 (COVID-19) vaccination has recently started worldwide. As the vaccine supply will be limited for a considerable period of time in many countries, it is important to devise the effective vaccination strategies that reduce the number of deaths and incidence of infection. One of the characteristics of COVID-19 is that the symptom, severity, and mortality of the disease differ by age. Thus, when the vaccination supply is limited, age-dependent vaccination priority strategy should be implemented to minimize the incidences and mortalities. In this study, we developed an age-structured model for describing the transmission dynamics of COVID-19, including vaccination. Using the model and actual epidemiological data in Korea, we estimated the infection probability for each age group under different levels of social distancing implemented in Korea and investigated the effective age-dependent vaccination strategies to reduce the confirmed cases and fatalities of COVID-19. We found that, in a lower level of social distancing, vaccination priority for the age groups with the highest transmission rates will reduce the incidence mostly, but, in higher levels of social distancing, prioritizing vaccination for the elderly age group reduces the infection incidences more effectively. To reduce mortalities, vaccination priority for the elderly age group is the best strategy in all scenarios of levels of social distancing. Furthermore, we investigated the effect of vaccine supply and efficacy on the reduction in incidence and mortality.
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http://dx.doi.org/10.3390/ijerph18084240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073596PMC
April 2021

Wolfberry () Consumption with a Healthy Dietary Pattern Lowers Oxidative Stress in Middle-Aged and Older Adults: A Randomized Controlled Trial.

Antioxidants (Basel) 2021 Apr 7;10(4). Epub 2021 Apr 7.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, 2 Science Drive 2, Singapore 117543, Singapore.

Incorporating zeaxanthin-rich wolfberry () into a healthy dietary pattern may augment its antioxidant potential. The present 16-week, parallel design randomized controlled trial aimed to investigate the impact of adhering to a healthy dietary pattern, either with or without whole dried wolfberry (15 g/d) on oxidative stress status (plasma malondialdehyde and 8-iso-prostaglandin F2α) in middle-aged and older adults. Changes to carotenoids status (plasma and skin carotenoids) and body composition were further evaluated to explore potential mechanisms which underlie the antioxidant properties of wolfberry. Plasma 8-iso-prostaglandin F2α, plasma zeaxanthin and skin carotenoids status were significantly raised in the wolfberry consuming group ( = 22; < 0.05) compared to the control group which showed no changes ( = 18). Likewise in the wolfberry group only, inverse association was observed between the change values of plasma zeaxanthin and plasma 8-iso-prostaglandin F2α (-0.21 (-0.43, 0.00) ng/µmol, regression coefficient (95% CI); = 0.05). Wolfberry consumption with a healthy dietary pattern may serve as a dietary strategy to attenuate lipid peroxidation among middle-aged and older adults who are at a heightened risk of oxidative stress induced age-related disorders. The antioxidant properties of wolfberry may be attributed to its rich zeaxanthin content.
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http://dx.doi.org/10.3390/antiox10040567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067708PMC
April 2021

Uncovering the dosage-dependent roles of Arid1a in gastric tumorigenesis for combinatorial drug therapy.

J Exp Med 2021 06;218(6)

Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Gastric cancer (GC) is one of the most common deadly cancers in the world. Although patient genomic data have identified AT-rich interaction domain 1A (ARID1A), a key chromatin remodeling complex subunit, as the second most frequently mutated gene after TP53, its in vivo role and relationship to TP53 in gastric tumorigenesis remains unclear. Establishing a novel mouse model that reflects the ARID1A heterozygous mutations found in the majority of human GC cases, we demonstrated that Arid1a heterozygosity facilitates tumor progression through a global loss of enhancers and subsequent suppression of the p53 and apoptosis pathways. Moreover, mouse genetic and single-cell analyses demonstrated that the homozygous deletion of Arid1a confers a competitive disadvantage through the activation of the p53 pathway, highlighting its distinct dosage-dependent roles. Using this unique vulnerability of Arid1a mutated GC cells, our combined treatment with the epigenetic inhibitor, TP064, and the p53 agonist, Nutlin-3, inhibited growth of Arid1a heterozygous tumor organoids, providing a novel therapeutic option for GC.
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http://dx.doi.org/10.1084/jem.20200219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034383PMC
June 2021

Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells.

Int J Mol Sci 2021 Mar 9;22(5). Epub 2021 Mar 9.

Department of Animal Science and Technology, Konkuk University, Seoul 05029, Korea.

The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, and the most efficient time for protein synthesis was determined by measuring cell, medium, and total protein at 0, 24, 48, 72, and 96 h. Time and dose tests showed that the 48 h incubation time and a 0.9 mM dose of L-Trp were the optimal values. The mechanism of milk protein synthesis was elucidated through proteomic analysis to identify the metabolic pathway involved. When L-Trp was supplemented, extracellular protein (medium protein) reached its peak at 48 h, whereas intracellular cell protein reached its peak at 96 h with all L-Trp doses. β-casein mRNA gene expression and genes related to milk protein synthesis, such as mammalian target of rapamycin (mTOR) and ribosomal protein 6 (RPS6) genes, were also stimulated ( < 0.05). Overall, there were 51 upregulated and 59 downregulated proteins, many of which are involved in protein synthesis. The results of protein pathway analysis showed that L-Trp stimulated glycolysis, the pentose phosphate pathway, and ATP synthesis, which are pathways involved in energy metabolism. Together, these results demonstrate that L-Trp supplementation, particularly at 0.9 mM, is an effective stimulus in β-casein synthesis by stimulating genes, proteins, and pathways related to protein and energy metabolism.
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http://dx.doi.org/10.3390/ijms22052751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963161PMC
March 2021

Postdural Puncture Headache Related to Procedure: Incidence and Risk Factors After Neuraxial Anesthesia and Spinal Procedures.

Pain Med 2021 Jun;22(6):1420-1425

Konkuk University School of Medicine.

Objective: Postdural puncture headache (PDPH) is a potential complication of certain neuraxial anesthesia and spinal procedures, and some risk factors for PDPH have been identified. However, there have been no detailed analyses of rates and risk factors of PDPH after various spinal and neuraxial anesthesia procedures.

Methods: Patient data from January 1, 2015, to December 31, 2017, were retrospectively analyzed. The patients underwent dural puncture procedures (spinal anesthesia, lumbar puncture [spinal tap], lumbar cerebrospinal fluid [CSF] drainage) or nondural puncture procedures (transforaminal epidural injection, interlaminar epidural injection, epidural catheterization with patient-controlled analgesia for delivery). PDPH incidence and risk factors were evaluated.

Results: For dural puncture procedures, PDPH incidence was 2.96%, and risk factors were younger age, female sex, and lumbar puncture. Larger needle gauge was a risk factor according to Student t-test but not during logistic regression analysis. PDPH incidence was higher after lumbar puncture using a 22 G Tuohy needle (4.63%) than after lumbar CSF drainage using an 18 G Tuohy needle (3.05%). For nondural puncture procedures, PDPH incidence was 0.53% and did not differ between procedure types; no risk factors were identified.

Conclusions: PDPH incidence and risk factors depended on the type of neuraxial anesthesia and spinal procedures. PDPH incidence after lumbar puncture using a 22 G Tuohy needle was higher than that after lumbar CSF drainage using an 18 G Tuohy needle, suggesting that catheter insertion may reduce PDPH risk. In non-dural puncture procedures, PDPH risk did not differ according to type of procedure, and no risk factors were found.
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http://dx.doi.org/10.1093/pm/pnaa437DOI Listing
June 2021

Animal Protein versus Plant Protein in Supporting Lean Mass and Muscle Strength: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Nutrients 2021 Feb 18;13(2). Epub 2021 Feb 18.

Department of Food Science & Technology, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.

Although animal protein is usually considered to be a more potent stimulator of muscle protein synthesis than plant protein, the effect of protein source on lean mass and muscle strength needs to be systematically reviewed. This study aimed to examine potential differences in the effect of animal vs. plant protein on lean mass and muscle strength, and the possible influence of resistance exercise training (RET) and age. The following databases were searched: PubMed, Embase, Scopus and CINAHL Plus with Full Text, and 3081 articles were screened. A total of 18 articles were selected for systematic review, of which, 16 were used for meta-analysis. Total protein intakes were generally above the recommended dietary allowance at the baseline and end of intervention. Results from the meta-analyses demonstrated that protein source did not affect changes in absolute lean mass or muscle strength. However, there was a favoring effect of animal protein on percent lean mass. RET had no influence on the results, while younger adults (<50 years) were found to gain absolute and percent lean mass with animal protein intake (weighted mean difference (WMD), 0.41 kg; 95% confidence interval (CI) 0.08 to 0.74; WMD 0.50%; 95% CI 0.00 to 1.01). Collectively, animal protein tends to be more beneficial for lean mass than plant protein, especially in younger adults.
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http://dx.doi.org/10.3390/nu13020661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926405PMC
February 2021

Real-world prevalence and burden of genital eczema in atopic dermatitis: A multicenter questionnaire-based study.

J Dermatol 2021 May 5;48(5):625-632. Epub 2021 Mar 5.

Department of Dermatology, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.

The involvement of genital lesions in patients with atopic dermatitis (AD) is poorly understood. Moreover, clinical characteristics, potentially related factors, and impact on the quality of life (QOL) of genital eczema in patients with AD are also largely unknown. This study aims to evaluate the prevalence and burden of genital eczema in patients with AD. A prospective cross-sectional study recruited a total of 220 patients diagnosed with AD. The participants were asked to complete the self-administrated questionnaire asking sociodemographic characteristics, details about their AD, and individual experiences of their genital eczema. Among 220 responders, 99 patients (45.00%) reported that they had experienced genital eczema at some time during the course of AD. Longer disease duration (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.13-4.62; p = 0.02), marital status (OR, 0.43; 95% CI, 0.21-0.89; p = 0.003), involvement of the trunk (OR, 3.44; 95% CI, 1.81-6.52; p = 0.001), and involvement of the nipple (OR, 6.20; 95% CI, 1.39-27.63; p = 0.017) were the significant associated factors for the presence of genital eczema among patients with AD. Of note, the severe impairment of genital eczema-specific QOL was observed in 28.29% of AD patients with genital eczema. Especially, female sex (OR, 2.22; 95% CI, 0.84-5.82; p = 0.04) was more associated with severe impairment of genital eczema-specific QOL. Many patients with AD suffer from the genital presentation of the disease. Moreover, genital involvement of the disease has a significant impact on the QOL of patients with AD. We suggest that more attention should be paid to the genital presentation of the disease to increase QOL and provide further delicate treatment of patients with AD.
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http://dx.doi.org/10.1111/1346-8138.15817DOI Listing
May 2021

Cerebellar 5HT-2A receptor mediates stress-induced onset of dystonia.

Sci Adv 2021 Mar 3;7(10). Epub 2021 Mar 3.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.

Stress is a key risk factor for dystonia, a debilitating motor disorder characterized by cocontractions of muscles leading to abnormal body posture. While the serotonin (5HT) system is known to control emotional responses to stress, its role in dystonia remains unclear. Here, we reveal that 5HT neurons in the dorsal raphe nuclei (DRN) send projections to the fastigial deep cerebellar nuclei (fDCN) and that photostimulation of 5HT-fDCN induces dystonia in wild-type mice. Moreover, we report that photoinhibition of 5HT-fDCN reduces dystonia in a1A mice, a genetic model of stress-induced dystonia, and administration of a 5HT-2A receptor inverse agonist (MDL100907; 0.1 to 1 mg/kg) or shRNA-mediated knockdown of the gene in fDCN can notably reduce the onset of dystonia in a1A mice. These results support the serotonin theory of dystonia and suggest strategies for alleviating symptoms in human patients by blocking 5HT-2A receptors.
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http://dx.doi.org/10.1126/sciadv.abb5735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929497PMC
March 2021

Anti-Inflammatory Effects of Antarctic Lichen Methanol Extract in Lipopolysaccharide-Stimulated RAW 264.7 Macrophage Cells and Zebrafish Model.

Biomed Res Int 2021 16;2021:8812090. Epub 2021 Feb 16.

Division of Life Sciences, Korea Polar Research Institute, Incheon 21990, Republic of Korea.

(UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E (PGE) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) B activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-B activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in and models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1155/2021/8812090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902135PMC
May 2021

Evaluation of multi-color genetically encoded Ca indicators in filamentous fungi.

Fungal Genet Biol 2021 Apr 16;149:103540. Epub 2021 Feb 16.

Department of Plant Pathology & Environmental Microbiology, The Pennsylvania State University, University Park, PA 16802, United States. Electronic address:

Genetically encoded Ca indicators (GECIs) enable long-term monitoring of cellular and subcellular dynamics of this second messenger in response to environmental and developmental cues without relying on exogenous dyes. Continued development and optimization in GECIs, combined with advances in gene manipulation, offer new opportunities for investigating the mechanism of Ca signaling in fungi, ranging from documenting Ca signatures under diverse conditions and genetic backgrounds to evaluating how changes in Ca signature impact calcium-binding proteins and subsequent cellular changes. Here, we attempted to express multi-color (green, yellow, blue, cyan, and red) circularly permuted fluorescent protein (FP)-based Ca indicators driven by multiple fungal promoters in Fusarium oxysporum, F. graminearum, and Neurospora crassa. Several variants were successfully expressed, with GCaMP5G driven by the Magnaporthe oryzae ribosomal protein 27 and F. verticillioides elongation factor-1α gene promoters being optimal for F. graminearum and F. oxysporum, respectively. Transformants expressing GCaMP5G were compared with those expressing YC3.60, a ratiometric Cameleon Ca indicator. Wild-type and three Ca signaling mutants of F. graminearum expressing GCaMP5G exhibited improved signal-to-noise and increased temporal and spatial resolution and are also more amenable to studies involving multiple FPs compared to strains expressing YC3.60.
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http://dx.doi.org/10.1016/j.fgb.2021.103540DOI Listing
April 2021

Genetic Variability Comparison of Wild and Cultured Far Eastern Catfish () of Korea using Microsatellite Marker.

Dev Reprod 2020 Dec 31;24(4):317-326. Epub 2020 Dec 31.

Inland Aquaculture Research Center, National Institute of Fisheries Science (NIFS), Changwon 51688, Korea.

The Far Eastern catfish () is an important commercial freshwater fish in Korea. Investigation of the genetic diversity of wild and cultured domestic catfish groups is essential for the restoration of fishery resources and for increasing local revenue. However, there are relatively few genetic diversity studies on wild and cultured catfish in Korea. In the present study, we analyzed the genetic diversity and association of wild and cultured catfish using five microsatellite markers. We determined that the number of alleles per locus ( ) ranged from 9 to 25, wherein the Jeonbuk catfish demonstrated the highest mean number of alleles per locus and the cultured catfish exhibited the lowest. The average expected heterozygosity () of the wild catfish samples was 0.907, and that of the cultured catfish showed was 0.875. The genetic distances (GD value) among populations of all catfish ranged from 0.138 to 0.242. Jeonnam and Jeonbuk wild catfish were located closest to each other, and the cultured group was separated from the other groups. In conclusion, the present study confirmed that the genetic diversity of wild and cultured catfish was maintained at a high level. In the case of the wild group, it is effective in maintaining diversity due to the continuous fry release by the local fish research institute. However, the genetic diversity of cultured catfish declined. Low diversity is associated with slow growth and weakened immunity, and therefore continuous monitoring is necessary.
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http://dx.doi.org/10.12717/DR.2020.24.4.317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837421PMC
December 2020

Susceptibility of Koi, Koi×Red Common Carp, and Red Common Carp×Koi to Koi Herpesvirus (KHV).

Dev Reprod 2020 Dec 31;24(4):277-286. Epub 2020 Dec 31.

Inland Aquaculture Research Center, National Institute of Fisheries Science (NIFS), Changwon 51688, Korea.

The disease-causing koi herpes virus (KHV), also known as cyprinid herpesvirus-3 (CyHV-3), causes mass mortality of koi and carp. Koi () is a host for KHV, one of 12 virus species in the family. We examined the effects of KHV disease koi (KK), and on koi×red common carp (KR) and red common carp×koi (RK) cross, using a virus challenge test. The infected fish had clinical signs that included gill necrosis and skin lesions. The RK and KR were highly more resistant (cumulative mortality: RK; 6% and KR; 8%) to KHV infection than KK fish (cumulative mortality: 28%). KHV DNA was confirmed in the tissues of all dead fish in groups by use of polymerase chain reaction (PCR), and the presence of the KHV protein in kidney was confirmed by immunohistochemistry. Histological analysis showed severe gill lesions and fusion of the lamellae in KK fish, but less severe damage in RK fish. In immunohistochemistry analysis, the KHV protein localized in the cytoplasm of infected kidney cells of KK, but the cross groups had lower levels of KHV antigen. Our data indicate that the cross groups had increased resistance to KHV disease.
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http://dx.doi.org/10.12717/DR.2020.24.4.277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837415PMC
December 2020

Prevalence of chronic post-thoracotomy pain in patients with traumatic multiple rib fractures in South Korea: a cross-sectional study.

Sci Rep 2021 Jan 28;11(1):2615. Epub 2021 Jan 28.

Department of Trauma Surgery, Cheju Halla Hospital, 65 Doryeong-ro, Jeju, 63127, South Korea.

Chronic post-thoracotomy pain is a debilitating condition after traumatic multiple rib fractures and surgery. We aimed to estimate the prevalence of chronic post-thoracotomy pain after traumatic multiple rib fractures in South Korea and explore factors associated with it. From October 2017 to June 2019, a cross-sectional survey of 100 adults, who had undergone thoracotomy due to traumatic fractures of two or more ribs 2 years to 3 months prior to the survey, was conducted in the regional trauma center in South Korea. In total, 80% and 65% patients reported any level and above moderate chronic pain, respectively. Quality of life was mostly below the normative value of the US general population. Forty-six percent patients had restrictive respiratory dysfunction, and 47% and 59% patients were classified as being at risk of above mild-level anxiety and depression, respectively. More than 70% of patients had a current opioid prescription. Multivariable logistic regression analysis showed weak evidence of association between acute, severe postoperative pain and chronic postsurgical pain (adjusted odds ratio 2.4, 95% confidence intervals 0.9 to 6.4). Collectively, chronic post-thoracotomy pain and associated incomplete recovery regarding respiratory, functional, and psychological outcomes were prevalent in patients with traumatic multiple rib fractures in South Korea.
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http://dx.doi.org/10.1038/s41598-021-82273-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844269PMC
January 2021

Engineering of Humanized Antibodies Against Human Interleukin 5 Receptor Alpha Subunit That Cause Potent Antibody-Dependent Cell-Mediated Cytotoxicity.

Front Immunol 2020 8;11:593748. Epub 2021 Jan 8.

Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.

Patients with severe eosinophilic asthma (SEA; characterized by persistent eosinophilia in blood and airway tissues) experience frequent asthma exacerbations with poor clinical outcomes. Interleukin 5 (IL-5) and IL-5 receptor alpha subunit (IL-5α) play key roles in eosinophilia maintenance, and relevant therapeutic strategies include the development of antibodies (Abs) against IL-5 or IL-5α to control eosinophilia. Benralizumab, an anti-IL-5α Ab that depletes eosinophils mainly Ab-dependent cell-mediated cytotoxicity and through blockage of IL-5 function on eosinophils, has been clinically approved for patients with SEA. Here, we report engineering of a new humanized anti-IL-5Rα Ab with potent biological activity. We first raised murine Abs against human IL-5Rα, humanized a leading murine Ab, and then further engineered the humanized Abs to enhance their affinity for IL-5Rα using the yeast surface display technology. The finally engineered version of the Ab, 5R65.7, with affinity ( ≈ 4.64 nM) stronger than that of a clinically relevant benralizumab analogue ( ≈ 26.8 nM) showed improved neutralizing activity toward IL-5-dependent cell proliferation in a reporter cell system. Domain level Ab epitope mapping revealed that 5R65.7 recognizes membrane-proximal domain 3 of IL-5Rα, distinct from domain I epitope of the benralizumab analogue. In assays with peripheral eosinophils from patients with SEA and healthy donors, 5R65.7 manifested more potent biological activities than the benralizumab analogue did, including inhibition of IL-5-dependent proliferation of eosinophils and induction of eosinophil apoptosis through autologous natural-killer-cell-mediated Ab-dependent cell-mediated cytotoxicity. Our study provides a potent anti-IL-5Rα Ab, 5R65.7, which is worthy of further testing in preclinical and clinical trials against SEA as a potential alternative to the current therapeutic arsenal.
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http://dx.doi.org/10.3389/fimmu.2020.593748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820887PMC
January 2021

Skin carotenoid status and plasma carotenoids: biomarkers of dietary carotenoids, fruits and vegetables for middle-aged and older Singaporean adults.

Br J Nutr 2021 Jan 14:1-10. Epub 2021 Jan 14.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, Science Drive 3, Singapore, Singapore.

Skin carotenoid status (SCS) measured by resonance Raman spectroscopy (RRS) may serve as an emerging alternative measurement for dietary carotenoid, fruit and vegetable (FV) intake although its application had not been assessed in a middle-aged and older population in Asia. This cross-sectional study aims to concurrently examine the use of SCS and plasma carotenoids to measure FV and carotenoid intake in a middle-aged and older population, taking into consideration potential socio-demographic and nutritional confounders. The study recruited 103 middle-aged and older adults (mean age: 58 years) in Singapore. Dietary carotenoids and FV, plasma carotenoid concentration and SCS were measured using 3-d food records, HPLC and a biophotonic scanner which utilised RRS, respectively. Adjusted for statistically defined socio-demographic covariates sex, age, BMI, prescription medication and cigarette smoking, plasma carotenoids and SCS showed positive associations with dietary total carotenoids (βplasma: 0·020 (95 % CI 0·000, 0·040) µmol/l/mg, P = 0·05; βskin: 265 (95 % CI 23, 506) arbitrary units/mg, P = 0·03) and FV (βplasma: 0·076 (95 % CI 0·021, 0·132) µmol/l per FV serving, P = 0·008; βskin: 1036 (95 % CI 363, 1708) arbitrary units/FV serving, P = 0·003). The associations of SCS with dietary carotenoid and FV intake were null with the inclusion of dietary PUFA, fibre and vitamin C as nutritional covariates (P > 0·05). This suggests a potential influence of these nutritional factors on carotenoid circulation and deposition in the skin. In conclusion, SCS, similar to plasma carotenoids, may serve as a biomarker for both dietary carotenoid and FV intake in a middle-aged and older Singaporean population.
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http://dx.doi.org/10.1017/S0007114521000143DOI Listing
January 2021

The frequency of defective genes in and genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in and genes on HIV-1 evolution.

J Ginseng Res 2021 Jan 8;45(1):149-155. Epub 2020 Apr 8.

Departments of Microbiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: We have reported that internal deletions in the , , and genes in HIV-1-infected patients are induced in those treated with Korean Red Ginseng (KRG). KRG delays the development of resistance mutations to antiretroviral drugs.

Methods: The - genes over 26 years in 20 hemophiliacs infected with HIV-1 from a single source were sequenced to investigate whether - genes were affected by KRG and KRG plus highly active antiretroviral therapy (ART) (hereafter called GCT) and compared the results with our previous data.

Results: A significantly higher number of in-frame small deletions were found in the - genes of KRG-treated patients than at the baseline, in control patients, and in ART-alone patients ( < 0.001). These were significantly reduced in GCT patients ( < 0.05). In contrast, sequences harboring a premature stop codon (SC) were more significant in GCT patients (10.1%) than in KRG-alone patients, control ( < 0.01), and ART-alone patients ( = 0.078 for peripheral blood mononuclear cells). The proportion of SC in Vpr was similar to that in Vif, whereas the proportion of sequences revealing SC in the genes was significantly lower than that in the genes ( < 0.01). The genetic distance was 1.8 times higher in the sequences harboring SC than in the sequences without SC ( < 0.001). Q135P in the gene is significantly associated with rapid progression to AIDS ( < 0.01).

Conclusion: Our data show that KRG might induce sΔ in the v- genes and that v- genes are similarly affected by lethal mutations.
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http://dx.doi.org/10.1016/j.jgr.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790868PMC
January 2021

Differential expression of microRNAs in the skin tissue of patients with severe papulopustular rosacea.

J Dermatol Sci 2021 Mar 23;101(3):210-213. Epub 2020 Dec 23.

Department of Dermatology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.12.005DOI Listing
March 2021

Skin carotenoids status as a potential surrogate marker for cardiovascular disease risk determination in middle-aged and older adults.

Nutr Metab Cardiovasc Dis 2021 02 26;31(2):592-601. Epub 2020 Oct 26.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore. Electronic address:

Background And Aims: Upon consumption, carotenoids, which may attenuate cardiovascular disease (CVD) risk, diffuse from the blood and accumulate in the skin. This study aimed to assess the associations between dietary, plasma, and skin carotenoids with CVD risk indicators and to examine the mediational role of plasma carotenoids in the relationship between skin carotenoids status (SCS) and CVD risk.

Methods And Results: Dietary, plasma, and skin carotenoids were assessed in a cross-sectional study from a community in Singapore (n = 103) aged 50 to 75 y. Multiple linear regression and binary logistics regression models were used to examine the associations between the carotenoids status with classical CVD risk factors and composite CVD risk indicators. After controlling for covariates, SCS and plasma carotenoids were inversely associated with systolic blood pressure (skin: P < 0.001; plasma: P < 0.05) and diastolic blood pressure (skin: P < 0.001; plasma: P < 0.005). Additionally, each increment of 1000 in SCS was associated with an odds ratio of 0.924 (P < 0.01) for metabolic syndrome diagnosis and 0.945 (P < 0.05) for moderate to high CVD risk classification. Associations between SCS and composite CVD risk indicators were null when adjusted for the corresponding plasma carotenoids, indicating complete mediation. Dietary carotenoids, however, showed no relationship with the CVD risk indicators.

Conclusion: Carotenoids bioavailability may be important for cardiovascular protection. SCS, driven by the corresponding plasma carotenoids, could be a potential noninvasive surrogate marker for CVD risk determination in middle-aged and older adults.

Clinical Trial Registration: NCT03554954, https://clinicaltrials.gov/.

Trial Registration Date: 13 June 2018.
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http://dx.doi.org/10.1016/j.numecd.2020.10.016DOI Listing
February 2021

Optimal storage sizing for indoor arena rainwater harvesting: Hydraulic simulation and economic assessment.

J Environ Manage 2021 Feb 23;280:111847. Epub 2020 Dec 23.

Water Innovation & Research Centre, Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom; KWR Water Research Institute, PO Box 1072, 3430, BB, Nieuwegein, the Netherlands.

This study demonstrates a large roof (30,000 m) rainwater harvesting (RWH) system in an indoor arena by considering three water demand scenarios (toilet flushing, irrigation and combined demand) via hydraulic and economic assessments. The water saving efficiency (WSE) of the RWH system for each scenario was estimated by a simulation model using historical daily rainfall data (1968-2018). Depending on the water demand, the WSE was found to be independent of tank size when the tank size exceeded 1000 m. The results suggest that the WSE of the RWH system is highly influenced by water demand scenarios, and a storage capacity of 400-1000 m would be enough for the applications considered in this study. The economic analysis results further showed that depending on the water demand, the RWH system with a rainwater storage capacity of between 100 and 600 m was more economically beneficial due to its positive cost saving values. The results also showed that depending on the water scenarios, the unit water cost between 0.37 and 0.40 £/m was lower than the mains water cost (0.40 £/m). As a result, the use of the RWH system with a tank between 400 and 600 m can be the most favourable range under the conditions considered in this study. Given the variations in water price, rainfall patterns and discount rates, the sensitivity analysis showed that water tariffs and discount rates play a significant role in reducing the unit water cost of the system, maintaining it lower than the mains water cost. A payback period analysis of the RWH system with a 600 m tank revealed that a 5% discount rate and a water price of 3 £/m would be enough to make the RWH system cost effective and that the capital cost could be returned within 10-11 years. This study highlights the need for preliminary sizing of a rainwater tank and an economic analysis of a large rooftop RWH system to maximise the benefits.
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http://dx.doi.org/10.1016/j.jenvman.2020.111847DOI Listing
February 2021

The Mediating Effect of Childcare Teachers' Resilience on the Relationship between Social Support in the Workplace and Their Self-Care.

Int J Environ Res Public Health 2020 11 17;17(22). Epub 2020 Nov 17.

Department of Child and Family Welfare, University of Suwon, Hwaseong-si 18323, Korea.

(1) Background: The purpose of this study is to examine the relationship between social support in the workplace for childcare teachers, resilience, and self-care. This study explores the inner mechanism that helps to strengthen self-care of childcare teachers, which enables teachers to provide quality care to children and promote their own wellbeing. (2) Methods: The survey was conducted from September to October 2018 for childcare teachers in Seoul and Gyeonggi Province using convenience sampling. Out of 550 questionnaires, 491 were returned, with 466 used for the analysis, excluding those with incomplete responses. The collected data were analyzed using descriptive statistics, correlation analysis, and mediation analysis. (3) Results: There were significant correlations between all variables. The mediation analysis showed a complete mediation of resilience. (4) Conclusion: Childcare teachers first have to take good care of themselves in order to perform well as a childcare professional. Educational materials and counseling programs tailored for childcare teachers need to be developed for better self-care and building greater resilience. Materials for directors of daycare centers, as well as teachers stressing the importance of social support for each other, will help childcare teachers' effective functioning in their professional and personal life. Prevention and intervention programs for self-care will eventually help lower the costs of healthcare in society.
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http://dx.doi.org/10.3390/ijerph17228513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698456PMC
November 2020

Inflammasome-mediated Inflammation by Malassezia in human keratinocytes: A comparative analysis with different strains.

Mycoses 2021 Mar 2;64(3):292-299. Epub 2020 Dec 2.

Department of Dermatology, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro-inflammatory cytokines and antimicrobial peptides by three different Malassezia species-M. restricta, M. globosa and M. sympodialis-in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin-domain-containing protein (NLRP)3-apoptosis-associated speck-like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)-1β secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, β-defensin 2, and LL-37. IL-8 mRNA and IL-22 protein significantly increased in the M. sympodialis-treated group, and Chemokine C-C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa- and M. restricta- treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro-inflammatory cytokines and chemokines, and antimicrobial peptides.
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http://dx.doi.org/10.1111/myc.13214DOI Listing
March 2021

Characteristics of female lung cancer in Korea: analysis of Korean National Lung Cancer Registry.

J Thorac Dis 2020 Sep;12(9):4612-4622

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Backgrounds: The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry.

Methods: In affiliation with the Korean Central Cancer Registry, the Korean Association for Lung Cancer constructed a registry into which 10% of the lung cancer cases in Korea were registered. Female lung cancer patients with valid smoking history were evaluated.

Results: Among 735 female lung cancer patients, 643 (87.5%) were never-smokers and 92 (12.5%) were smokers. The median survival was significantly longer in the never-smoker group (28 14 months; P<0.001). Among 683 patients with non-small cell lung cancer (NSCLC), the never-smoker group showed significantly longer median survival (29 14 months; P=0.002) and a higher proportion of stage I cancer (40.3% 25.7%; P<0.001). Survival analysis of the NSCLC patients showed that smoking status, receiving only supportive care, EGFR mutation status, lung cancer stage, and forced vital capacity (FVC) (%) were significantly associated with mortality in the multivariate analysis (P=0.025, HR 2.39, 95% CI: 1.12-5.11; P=0.017, HR 3.14, 95% CI: 1.22-8.06; P=0.033, HR 0.63, 95% CI: 0.41-0.96; P<0.001, HR 11.88, 95% CI: 5.79-24.38; P=0.002, HR 0.98, 95% CI: 0.96-0.99, respectively).

Conclusions: In Korean women with NSCLC, smoking status, not receiving active anticancer treatment, EGFR mutation status, lung cancer stage, and pulmonary function were significantly associated with mortality.
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http://dx.doi.org/10.21037/jtd-20-1671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578488PMC
September 2020

Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts.

Int J Mol Sci 2020 Oct 28;21(21). Epub 2020 Oct 28.

Department of Dermatology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea.

Keloid is a representative chronic fibroproliferative condition that occurs after tissue injury. Emerging evidence showed that activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pro-inflammatory response in injured tissues. However, the role of NLRP3 inflammasome in keloid progression remains unclear. Notch signaling, which activates NLRP3 inflammasome, is known to contribute to scar formation in keloid, but the cause of enhanced Notch signaling in keloid is not clear. We sought to investigate whether autophagy regulates Notch1 signaling in keloid fibroblasts and determine whether Notch1 signaling might regulate NLRP3 inflammasomes and myofibroblast differentiation. An in vitro model of keloid was established by culturing primary keloid fibroblasts from patients. Expression levels of Notch1, NLRP3 inflammasome proteins, pro-inflammatory cytokines, and myofibroblast markers in keloid fibroblasts were examined and compared with those in normal fibroblasts. Autophagy known to mediate Notch1 degradation was also monitored in fibroblasts. Small interfering RNA (siRNA) targeting Notch1 was used to transfect keloid fibroblasts to further examine the role of Notch signaling in NLRP3 inflammasome activation. Expression levels of Notch1 and NLRP3 inflammasome in keloid fibroblasts increased compared to those in normal fibroblasts. Such increases were accompanied by increased LC3 levels and reduced autophagic flux. Notch1 silencing in keloid fibroblasts by siRNA transfection significantly suppressed increased levels of overall NLRP3 inflammasome complex proteins, NF-kB, and α-smooth muscle actin. Autophagy induction by rapamycin treatment in keloid fibroblasts effectively suppressed expression levels of Notch1 and NLRP3 inflammasome proteins. Decreased autophagy activity in keloid can result in Notch1-mediated myofibroblast activation and NLRP3 inflammasome signaling activation which is critical for chronic inflammation. Collectively, these results identify Notch1 as a novel activator of NLRP3 inflammasome signaling leading to chronic tissue damage and myofibroblast differentiation in keloid progression.
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http://dx.doi.org/10.3390/ijms21218050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663397PMC
October 2020