Publications by authors named "Chan-Hee Lee"

136 Publications

Risk of Pregnancy Complications and Low Birth Weight Offsprings in Korean Women With Rheumatic Diseases: A Nationwide Population-Based Study.

J Korean Med Sci 2022 Jan 10;37(2):e18. Epub 2022 Jan 10.

Division of Rheumatology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea.

Background: To determine the risk of pregnancy complications and adverse offspring outcomes in Korean women with rheumatic diseases (RDs).

Methods: Women aged 20-44 years with pregnancies ending in delivery were identified from the National Health Insurance Service-National Health Information Database (2009-2016). Women with RD including systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SPRA), and ankylosing spondylitis (AS) (n = 4,284) were age-matched with controls (n = 26,023). Outcome variables included threatened abortion (TA), preterm birth (PB), preeclampsia/eclampsia (PE/E), intrauterine growth retardation (IGR), urinary tract infection, low birth weight (LBW) offsprings, and offspring death within 1 year of birth.

Results: Women with RDs had increased risks for cesarean section delivery (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), TA (OR, 1.4; 95% CI, 1.2-1.5), PB (OR, 2.4; 95% CI, 1.9-3.2), PE/E (OR, 4.4; 95% CI, 3.3-5.9), and IGR (OR, 2.4; 95% CI, 2.0-3.1) than the controls. The risk of pregnancy complications was increased in SLE and SPRA pregnancies but not in AS pregnancies. Offsprings of women with RDs had an increased risk of LBW (OR, 4.0; 95% CI, 3.2-4.9). The offspring mortality rate within 1 year of birth was higher in women with RDs (6.2/10,000 persons) than in the controls (4.9/10,000 persons).

Conclusion: Women with RDs are at a risk of developing pregnancy complications, and the risk of LBW offsprings and offspring death within 1 year of birth is increased in these women. Therefore, this population requires special attention during their childbearing years.
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http://dx.doi.org/10.3346/jkms.2022.37.e18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748664PMC
January 2022

Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient-Derived Chips.

Adv Healthc Mater 2021 Dec 28:e2102226. Epub 2021 Dec 28.

Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Glioblastoma (GBM) is one of the most intractable tumor types due to the progressive drug resistance upon tumor mass expansion. Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen-generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor-on-a-chip model enables user-specified alternation of clinic-derived samples. This study utilizes patient-derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size-proportional expression of hypoxia-inducible factor-1a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.
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http://dx.doi.org/10.1002/adhm.202102226DOI Listing
December 2021

Long-term effects of the mean hemoglobin A1c levels after percutaneous coronary intervention in patients with diabetes.

Korean J Intern Med 2021 Nov 14;36(6):1365-1376. Epub 2021 Oct 14.

Yeungnam University College of Medicine, Daegu, Korea.

Background/aims: The clinical benefit of strict blood glucose-lowering therapy for patients with coronary artery disease (CAD) is still debated. We aimed to evaluate the long-term outcomes of patients with diabetes who underwent percutaneous coronary intervention (PCI), according to the mean hemoglobin A1c (HbA1c) level after PCI.

Methods: We evaluated 675 diabetes patients with CAD treated with PCI. We categorized the study population into three groups based on the mean observed HbA1c levels during the follow-up duration, as follows: aggressive control (AC) group (HbA1c level < 6.5%, n = 148), moderate control (MC) group (HbA1c level ≥ 6.5% and < 7.0%, n = 138), and uncontrolled (UC) group (HbA1c level ≥ 7.0%, n = 389). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as cardiac death, myocardial infarction, repeat target vessel revascularization, and stroke.

Results: The mean HbA1c level of the AC group was significantly lower than that of the MC and UC groups (6.04% ± 0.36% vs. 6.74% ± 0.14% vs. 8.39% ± 1.20%, p < 0.001). The incidence of MACCEs was significantly lower in the AC group than in the MC and UC groups (16.0% vs. 24.3% vs. 26.3%, p = 0.010), mostly driven by the incidence of stroke (4.4% vs. 14.0% vs. 11.4%, p = 0.013). Multivariate Cox regression analysis showed that only the AC group was associated with a reduced rate of MACCEs (hazard ratio, 0.499; 95% confidence interval, 0.316 to 0.786; p = 0.004) compared with the UC group.

Conclusion: Our study showed that intensive glycemic control (HbA1c level < 6.5%) is associated with improved clinical outcomes after PCI in patients with diabetes.
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http://dx.doi.org/10.3904/kjim.2020.694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588978PMC
November 2021

Clinical Impact of Dysglycemia in Patients with an Acute Myocardial Infarction (Diabetes Metab J 2021;45:270-4).

Authors:
Chan-Hee Lee

Diabetes Metab J 2021 09 30;45(5):791-792. Epub 2021 Sep 30.

Divisions of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Korea.

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http://dx.doi.org/10.4093/dmj.2021.0190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497929PMC
September 2021

Electrocardiographic Manifestations in Patients with COVID-19: Daegu in South Korea.

Korean Circ J 2021 Oct;51(10):851-862

Division of Cardiology, Daegu Catholic University College of Medicine, Daegu, Korea.

Background And Objectives: As the coronavirus disease 2019 (COVID-19) spreads worldwide, cardiac injury in patients infected with COVID-19 becomes a significant concern. Thus, this study investigates the impact of several electrocardiogram (ECG) parameters and disease severity in COVID-19 patients.

Methods: Seven medical centers in Daegu admitted 822 patients with COVID-19 between February and April 2020. This study examined 267 patients among them who underwent an ECG test and evaluated their biochemical parameters like C-reactive protein (CRP), log N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), cardiac enzyme, and ECG parameters (heart rate, PR interval, QRS interval, T inversion, QT interval, and Tpe [the interval between peak to end in a T wave]).

Results: Those patients were divided into 3 groups of mild (100 patients), moderate (89 patients), and severe (78 patients) according to clinical severity score. The level of CRP, log NT-proBNP, and creatinine kinase-myocardial band were significantly increased in severe patients. Meanwhile, severe patients exhibited prolonged QT intervals (QTc) and Tpe (Tpe-c) compared to mild or moderate patients. Moreover, deceased patients (58; 21.7%) showed increased dispersion of QTc and Tpe-c compared with surviving patients (78.2±41.1 vs. 40.8±24.6 ms and 60.2±37.3 vs. 40.8±24.5 ms, both p<0.05, respectively). The QTc dispersion of more than 56.1 ms could predict the mortality in multivariate analysis (odd ratio, 11.55; 95% confidence interval, 3.746-42.306).

Conclusions: COVID-19 infections could involve cardiac injuries, especially cardiac repolarization abnormalities. A prolonged QTc dispersion could be an independent predictable factor of mortality.
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http://dx.doi.org/10.4070/kcj.2021.0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484995PMC
October 2021

Coenzyme Q10 ameliorates the quality of mouse oocytes during culture.

Zygote 2021 Aug 25:1-9. Epub 2021 Aug 25.

Department of Biological Science, Inje University, 197 Inje-ro, Gimhae, Gyeongnam, 50834, Republic of Korea.

Oxidative stress causes several diseases and dysfunctions in cells, including oocytes. Clearly, oxidative stress influences oocyte quality during in vitro maturation and fertilization. Here we tested the ability of coenzyme Q10 (CoQ10) to reduce reactive oxygen species (ROS) and improve mouse oocyte quality during in vitro culture. Treatment with 50 μM CoQ10 efficiently reduced ROS levels in oocytes cultured in vitro. The fertilizable form of an oocyte usually contains a cortical granule-free domain (CGFD). CoQ10 enhanced the ratio of CGFD-oocytes from 35% to 45%. However, the hardening of the zona pellucida in oocytes was not affected by CoQ10 treatment. The in vitro maturation capacity of oocytes, which was determined by the first polar body extrusion, was enhanced from 48.9% to 75.7% by the addition of CoQ10 to the culture medium. During the parthenogenesis process, the number of two-cell embryos was increased by CoQ10 from 43.5% to 67.3%. Additionally, treatment with CoQ10 increased the expression of Bcl2 and Sirt1 in cumulus cells. These results suggested that CoQ10 had a positive effect on ROS reduction, maturation rate and two-cell embryo formation in mouse oocyte culture.
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http://dx.doi.org/10.1017/S0967199421000617DOI Listing
August 2021

Selective Regional Loss of Cortical Synapses Lacking Presynaptic Mitochondria in the 5xFAD Mouse Model.

Front Neuroanat 2021 25;15:690168. Epub 2021 Jun 25.

Neural Circuits Research Group, Korea Brain Research Institute, Daegu, South Korea.

Synaptic loss in Alzheimer's disease (AD) is strongly correlated with cognitive impairment. Accumulating evidence indicates that amyloid pathology leads to synaptic degeneration and mitochondrial damage in AD. However, it remains unclear whether synapses and presynaptic mitochondria are differentially affected in various cortical regions of the AD brain at the ultrastructural level. Using serial block-face scanning electron microscopy, we assessed synaptic structures in the medial prefrontal cortex (mPFC) and primary visual cortex (V1) of the 5xFAD mouse model of AD. At 6 months of age, 5xFAD mice exhibited significantly elevated levels of amyloid deposition in layer 2/3 of the mPFC but not V1. Accordingly, three-dimensional reconstruction of synaptic connectivity revealed a significant reduction in excitatory synaptic density in layer 2 of the mPFC, but not V1, of male transgenic mice. Notably, the density of synapses lacking presynaptic mitochondria was selectively decreased in the mPFC of 5xFAD mice, with no change in the density of mitochondria-containing synapses. Further classification of spines into shape categories confirmed a preferential loss of thin spines whose presynaptic boutons were largely devoid of mitochondria in the 5xFAD mPFC. Furthermore, the number of mitochondria per bouton in spared mitochondria-containing boutons was reduced in the mPFC, but not V1, of 5xFAD mice. Collectively, these results highlight region-specific vulnerability of cortical synapses to amyloid deposition and suggest that the presence of presynaptic mitochondria may affect synaptic degeneration in AD.
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http://dx.doi.org/10.3389/fnana.2021.690168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267061PMC
June 2021

Burden of comorbidities and medication use in childbearing women with rheumatic diseases: a nationwide population-based study.

Korean J Intern Med 2021 Jul 9. Epub 2021 Jul 9.

Division of Rheumatology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.

Background/aims: We aimed to estimate the prevalence of comorbidities and medication use in Korean women with rheumatic diseases (RDs) during their childbearing years.

Methods: We included women aged 20 to 44 years with seropositive rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) (n = 41,547) and age-matched women without seropositive RA, SLE, and AS (n = 208,941) from the National Health Insurance Service-National Health Information Database (2009 to 2016). The prevalence of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CSs), and disease-modifying anti-rheumatic drugs (DMARDs) were estimated.

Results: Women of childbearing age with RDs were more likely to have at least one of the measured comorbidities than the controls (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.9 to 3.1). The OR (95% CI) was 2.9 (2.8 to 3.0) for HTN, 2.8 (2.7 to 2.9) for HLD, 1.4 (1.4 to 1.5) for DM, and 1.3 (1.3 to 1.4) for cancer. The SLE group had the highest prevalence and odds of all four measured comorbidities. Almost all (97.9%) women of childbearing age with RDs were taking RD-related medications (NSAIDs, 81.6%; CSs, 77.8%; DMARDs, 87.3%). The RD group was 13.8 times more likely to take NSAIDs and 68.2 times more likely to take CSs than the controls. Use of NSAIDs was more prevalent in RA and AS than SLE, whereas use of CSs and DMARDs was more prevalent in RA and SLE than AS.

Conclusions: Korean women with RDs have a greater burden of comorbidities and medication use during their childbearing years than women without RDs of the same age.
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http://dx.doi.org/10.3904/kjim.2021.089DOI Listing
July 2021

Genetic changes in plaque-purified varicella vaccine strain Suduvax during in vitro propagation in cell culture.

J Microbiol 2021 Jul 1;59(7):702-707. Epub 2021 Jun 1.

Department of Microbiology, Chungbuk National University, Cheongju, 28644, Republic of Korea.

Infection by varicella-zoster virus (VZV) can be prevented by using live attenuated vaccines. VZV vaccine strains are known to evolve rapidly in vivo, however, their genetic and biological effects are not known. In this study, the plaque-purified vaccine strain Suduvax (PPS) was used to understand the genetic changes that occur during the process of propagation in in vitro cell culture. Full genome sequences of three different passages (p4, p30, and p60) of PPS were determined and compared for genetic changes. Mutations were found at 59 positions. The number of genetically polymorphic sites (GPS) and the average of minor allele frequency (MAF) at GPSs were not significantly altered after passaging in cell culture up to p60. The number of variant nucleotide positions (VNPs), wherein GPS was found in at least one passage of PPS, was 149. Overall, MAF changed by less than 5% at 52 VNPs, increased by more than 5% at 42 VNPs, and decreased by more than 5% at 55 VNPs in p60, compared with that seen in p4. More complicated patterns of changes in MAF were observed when genetic polymorphism at 149 VNPs was analyzed among the three passages. However, MAF decreased and mixed genotypes became unequivocally fixed to vaccine type in 23 vaccine-specific positions in higher passages of PPS. Plaque-purified Suduvax appeared to adapt to better replication during in vitro cell culture. Further studies with other vaccine strains and in vivo studies will help to understand the evolution of the VZV vaccine.
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http://dx.doi.org/10.1007/s12275-021-1062-3DOI Listing
July 2021

Clinical impact of blood pressure variability in patients with COVID-19 and hypertension.

Blood Press Monit 2021 Oct;26(5):348-356

Division of Rheumatology and Infectious Disease, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea.

Objective: This study aimed to investigate the relationship between blood pressure variability (BPV) and clinical outcomes in patients with coronavirus disease 2019 (COVID-19) and hypertension.

Methods: A total of 136 patients hospitalized with COVID-19 were enrolled in this study. Patients were grouped according to the presence of hypertension and BPV. Mean arterial pressure (MAP) measured at 8 a.m. and 8 p.m. was analyzed, and BPV was calculated as the coefficient of variation of MAP (MAPCV). High BPV was defined as MAPCV values above the median. We compared the age, level of C-reactive protein (CRP), creatine kinase-MB (CK-MB), N-terminal pro-B type natriuretic peptide (NT-proBNP), creatinine and in-hospital mortality and investigated the relationship among the groups.

Results: COVID-19 patients with hypertension were older (70 ± 12 vs. 53 ± 17 years; P < 0.001), had higher levels of CRP (9.4 ± 9.2 vs. 5.3 ± 8.2 mg/dL; P = 0.009), MAPCV (11.4 ± 4.8 vs. 8.9 ± 3.2; P = 0.002), and higher in-hospital mortality (19.6% vs. 5.9%; P = 0.013) than those without hypertension. There was a proportional relationship between BPV and age, levels of CRP, CK-MB, NT-proBNP, creatinine and in-hospital mortality (all, P < 0.05). In Cox regression analysis, advanced age [≥80 years, hazard ratio (HR) 10.4, 95% confidence interval (CI) 2.264-47.772, P = 0.003] and higher MAPCV (HR 1.617, 95% CI, 1.281-2.040, P < 0.001) were significantly associated with in-hospital mortality.

Conclusion: High BPV in COVID-19 patients with hypertension is significantly associated with in-hospital mortality. Advanced age and systemic inflammation are proportional to high BPV. Additional attention is needed for COVID-19 patients with hypertension and high BPV.
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http://dx.doi.org/10.1097/MBP.0000000000000544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423029PMC
October 2021

Seizure during hyperbaric oxygen therapy: experience at a single academic hospital in Korea.

Undersea Hyperb Med 2021 First Quarter;48(1):43-51

Department of Emergency Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Background: Hyperbaric oxygen (HBO2) therapy is a safe and well-tolerated treatment modality. Seizures, one of the most severe central nervous system side effects of HBO2 therapy, can occur. Episodes of seizures during HBO2 therapy have not yet been reported in countries such as Korea, where hyperbaric medicine is still in the developmental stage.

Methods: The registry data of all patients treated with HBO2 therapy in a tertiary academic hospital in Korea were prospectively collected, and patients who developed seizures during HBO2 therapy between October 2016 and December 2019 were evaluated. In addition, we reviewed previous studies on occurrence of seizures during HBO2 therapy.

Results: During the study period, a total of 10,425 treatments were provided to 1,308 patients. The most frequently treated indication was carbon monoxide (CO) poisoning ABSTRACT (n=547, 41.8%). During the HBO2 therapy sessions (total: 10,425), five seizure episodes occurred (patients with CO poisoning: n=4; patients with arterial gas embolism [AGE]: n=1). The frequency of seizures in patients with CO poisoning (0.148%) and AGE (3.448%) was significantly higher than that in patients with all indications (0.048%) (p=0.001). None of the patients had lasting effects due to the seizures.

Conclusion: Our study revealed a similar frequency rate in terms of all indications and CO poisoning, and a slightly higher rate in AGE. Seizures were observed in patients with CO poisoning and AGE. Therefore, if clinicians plan to operate a hyperbaric center in a country like Korea, where there are several patients with acute CO poisoning, they should be prepared to handle seizures that may occur during HBO2 therapy.
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March 2021

Evaluating enzyme stabilizations in calcium carbonate: Comparing in situ and crosslinking mediated immobilization.

Int J Biol Macromol 2021 Apr 5;175:341-350. Epub 2021 Feb 5.

Department of Food Biotechnology, Dong-A University, Busan 49315, Republic of Korea. Electronic address:

Enzyme immobilization using inorganic materials has been shown to preserve enzyme activity improving and improve their practical applications in biocatalytic process designs. Proper immobilization methods have been used to obtain high recycling and storage stability. In this study, we compared the activity and stability of in situ or crosslink-immobilized enzymes in a CaCO biomineral carrier. More than 30% of the initial enzyme activity was preserved for both the systems after 180 days upon 15 activity measurements at room temperature, confirming the improved stability of these enzyme systems (100 mM phosphate buffer, pH 8.0); however, differences in enzyme loading, activity, and characteristics were observed for each of these methods. Each system exhibited efficacy of 80% and 20%, respectively. Based on the same amount of immobilized enzyme (0.2 mg), the specific activities of hydrolysis of p-nitrophenyl butyrate substrate at room temperature of in situ immobilized carboxyl esterase (CE) and crosslinked CE were 11.37 and 7.63 mM min mg, respectively (100 mM phosphate buffer, pH 8.0). Moreover, based on the kinetic behavior, in situ immobilized CE exhibited improved catalytic efficiency (Vmax Km) of the enzyme, exhibiting 4-fold higher activity and efficiency values than those of the CE immobilized in CaCO. This is the first study to describe the stabilization of enzymes in CaCO and compare the enzyme kinetics and efficiencies between in situ immobilization and crosslinking in CaCO carriers.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.028DOI Listing
April 2021

Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced High-Turnover Metabolism.

Cell Metab 2021 02;33(2):334-349.e6

Division of Endocrinology and Metabolism, Department of Internal Medicine, Diabetes Center, Asan Medical Center and University of Ulsan College of Medicine, Seoul 05505, Korea. Electronic address:

Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPR) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPR and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.
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http://dx.doi.org/10.1016/j.cmet.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959183PMC
February 2021

Incidence and prevalence of systemic lupus erythematosus among Korean women in childbearing years: A nationwide population-based study.

Lupus 2021 Apr 18;30(4):674-679. Epub 2021 Jan 18.

Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, South Korea.

Background: Most women with systemic lupus erythematosus (SLE) are diagnosed with the disease in their reproductive years, but the incidence and prevalence of SLE among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of SLE among the Korean women of childbearing age.

Methods: Women aged 20 to 44 years with SLE were identified from National Health Insurance Service - National Health Information Database (2009-2016), which contain health information of approximately 97% of the Korean population. SLE was defined by International Classification of Diseases, 10th revision code, M32. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age.

Results: A total of 12,756 women with SLE were identified. The incidence of SLE from 2011 to 2016 among women in childbearing years was 8.18/100,000 person-years (95% CI 7.94-8.43), with the highest incidence in 2016 (8.56/100,000 person-years, 95% CI 7.95-9.17) and the lowest incidence in 2012 (7.85/100,000 person-years, 95% CI 7.28-8.42). The prevalence of SLE from 2009 to 2016 among women in childbearing years was 77.07/100,000 person-years (95% CI 75.76-78.39), with the highest prevalence in 2014 (79.47/100,000 person-years, 95% CI 77.64-81.30) and the lowest in 2010 (74.19/100,000 person-years, 95% CI 72.45-75.93). The peak age for SLE incidence was between 25-39 years, and lower incidence was seen in the early (20-24 years) and late (40-44 years) childbearing age periods. There was an increasing trend in prevalence according to age in women of childbearing age, with the highest prevalence occurring in the 40-44 age group.

Conclusions: The risk and burden of SLE are high among women during their childbearing years. This calls for special attention to this particular population group when allocating health resources.
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http://dx.doi.org/10.1177/0961203320984845DOI Listing
April 2021

Primary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus.

Nat Commun 2020 11 13;11(1):5772. Epub 2020 Nov 13.

Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul, 05505, Korea.

Hypothalamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights. The non-motile primary cilium is a critical sensory organelle on the cell surface. An association between ciliary defects and obesity has been suggested, but the underlying mechanisms are not fully understood. Here we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits. Our findings reveal a mechanism of early life programming of adult adiposity, which is mediated by primary cilia in developing hypothalamic neurons.
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http://dx.doi.org/10.1038/s41467-020-19638-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666216PMC
November 2020

Immobilization and Stabilization of Enzyme in Biomineralized Calcium Carbonate Microspheres.

Front Bioeng Biotechnol 2020 9;8:553591. Epub 2020 Oct 9.

Department of Food Biotechnology, Dong-A University, Busan, South Korea.

Biomineralized uniform and well-organized calcium carbonate microspheres were synthesized for enzyme immobilization, and the immobilized enzyme was successfully stabilized. The physicochemical parameters of calcium carbonate were studied using scanning electron microscopy with energy-dispersive X-ray spectroscopy, particle size analysis, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, and surface area measurement. Additionally, Barrett-Joyner-Halenda adsorption/desorption analysis showed that the calcium carbonate microspheres provided efficient mesopore space for enzyme loading. As a model enzyme, carboxyl esterase (CE) was entrapped and then cross-linked to form an enzyme structure. In this aggregate, the cross-linked enzymes cannot leach out from mesopores, resulting in enzyme stability. The hydrolytic activities of the free and cross-linked enzymes were analyzed over broad temperature and pH ranges. The cross-linked enzyme displayed better activity than the free enzyme. Furthermore, the immobilized CE was found to be stable for more than 30 days, preserving 60% of its initial activity even after being reused more than 10 times. This report is expected to be the first demonstration of a stabilized cross-linked enzyme system in calcium carbonate microspheres, which can be applied in enzyme catalyzed reactions involved in bioprocessing, bioremediation, and bioconversion.
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http://dx.doi.org/10.3389/fbioe.2020.553591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581938PMC
October 2020

Clinical Implication of 'Obesity Paradox' in Elderly Patients With Acute Myocardial Infarction.

Heart Lung Circ 2021 Apr 1;30(4):481-488. Epub 2020 Oct 1.

Chonbuk National University Hospital, Jeonju, Republic of Korea.

Background: The clinical impact of body mass index (BMI), especially in the elderly with acute myocardial infarction (AMI), has not been sufficiently evaluated. The purpose of this study was to elucidate the clinical impact of BMI in very old patients (≥80 years) with AMI.

Methods: The study analysed 2,489 AMI patients aged ≥80 years from the Korea Acute Myocardial Infarction Registry and the Korea Working Group on Myocardial Infarction (KAMIR/KorMI) registries between November 2005 and March 2012. The study population was categorised into four groups based on their BMI: underweight (n=301), normal weight (n=1,150), overweight (n=890), and obese (n=148). The primary endpoint was major adverse cardiovascular event (MACE), a composite of cardiac death, myocardial infarction, target lesion revascularisation, and target vessel revascularisation.

Results: Baseline characteristics among the four groups were similar, except for hypertension (45.1 vs 58.4 vs 66.2 vs 69.9%, respectively; p<0.001) and diabetes (16.6 vs 23.6 vs 30.7 vs 35.1%, respectively; p<0.001). Coronary care unit length of stay was significantly different among the four groups during hospitalisation (5.3±5.9 vs 4.8±6.8 vs 4.2±4.0 vs 3.5±2.1 days; p=0.007). MACE (16.9 vs 14.9 vs 13.7 vs 8.8%; p=0.115) and cardiac death (10.3 vs 8.4 vs 7.9 vs 4.1%; p=0.043) less frequently occurred in the obese group than in other groups during the 1-year follow-up. A multivariate regression model showed obese status (BMI ≥27.5 kg/m) as an independent predictor of reduced MACE (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.06-0.69; p=0.010) along with reduced left ventricular ejection fraction (≤40%) as a predictor of increased MACE (HR,1.87; 95% CI, 1.31-2.68; p=0.001).

Conclusion: Body mass index in elderly patients with acute myocardial infarction was significantly associated with coronary care unit stay and clinical cardiovascular outcomes.
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http://dx.doi.org/10.1016/j.hlc.2020.08.013DOI Listing
April 2021

Altered presynaptic function and number of mitochondria in the medial prefrontal cortex of adult Cyfip2 heterozygous mice.

Mol Brain 2020 09 11;13(1):123. Epub 2020 Sep 11.

Department of Neuroscience, College of Medicine, Korea University, 73, Goryeodae-ro, Seongbuk-gu, Seoul, 02841, South Korea.

Variants of the cytoplasmic FMR1-interacting protein (CYFIP) gene family, CYFIP1 and CYFIP2, are associated with numerous neurodevelopmental and neuropsychiatric disorders. According to several studies, CYFIP1 regulates the development and function of both pre- and post-synapses in neurons. Furthermore, various studies have evaluated CYFIP2 functions in the postsynaptic compartment, such as regulating dendritic spine morphology; however, no study has evaluated whether and how CYFIP2 affects presynaptic functions. To address this issue, in this study, we have focused on the presynapses of layer 5 neurons of the medial prefrontal cortex (mPFC) in adult Cyfip2 heterozygous (Cyfip2) mice. Electrophysiological analyses revealed an enhancement in the presynaptic short-term plasticity induced by high-frequency stimuli in Cyfip2 neurons compared with wild-type neurons. Since presynaptic mitochondria play an important role in buffering presynaptic Ca, which is directly associated with the short-term plasticity, we analyzed presynaptic mitochondria using electron microscopic images of the mPFC. Compared with wild-type mice, the number, but not the volume or cristae density, of mitochondria in both presynaptic boutons and axonal processes in the mPFC layer 5 of Cyfip2 mice was reduced. Consistent with an identification of mitochondrial proteins in a previously established CYFIP2 interactome, CYFIP2 was detected in a biochemically enriched mitochondrial fraction of the mouse mPFC. Collectively, these results suggest roles for CYFIP2 in regulating presynaptic functions, which may involve presynaptic mitochondrial changes.
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http://dx.doi.org/10.1186/s13041-020-00668-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488858PMC
September 2020

Clinical Impact of Dysglycemia in Patients with an Acute Myocardial Infarction.

Diabetes Metab J 2021 03 16;45(2):270-274. Epub 2020 Apr 16.

Yeungnam University College of Medicine, Daegu, Korea.

This study aimed to determine the impact of dysglycemia on myocardial injury and cardiac dysfunction in acute myocardial infarctions (AMIs). From 2005 to 2016, a total of 1,593 patients with AMIs who underwent percutaneous coronary intervention were enrolled. The patients were classified into five groups according to the admission glucose level: ≤80, 81 to 140, 141 to 200, 201 to 260, and ≥261 mg/dL. The clinical and echocardiographic parameters and 30-day mortality were analyzed. The peak troponin I and white blood cell levels had a positive linear relationship to the admission glucose level. The left ventricular ejection fraction had an inverted U-shape trend, and the E/E' ratio was U-shaped based on euglycemia. The 30-day mortality also increased as the admission glucose increased, and the cut-off value for predicting the mortality was 202.5 mg/dL. Dysglycemia, especially hyperglycemia, appears to be associated with myocardial injury and could be another adjunctive parameter for predicting mortality in patients with AMIs.
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http://dx.doi.org/10.4093/dmj.2019.0164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024153PMC
March 2021

Cellular Contributors to Hypothalamic Inflammation in Obesity.

Mol Cells 2020 May;43(5):431-437

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

The hypothalamus is a crucial organ for the maintenance of appropriate body fat storage. Neurons in the hypothalamic arcuate nucleus (ARH) detect energy shortage or surplus via the circulating concentrations of metabolic hormones and nutrients, and then coordinate energy intake and expenditure to maintain energy homeostasis. Malfunction or loss of hypothalamic ARH neurons results in obesity. Accumulated evidence suggests that hypothalamic inflammation is a key pathological mechanism that links chronic overconsumption of a high-fat diet (HFD) with the development of obesity and related metabolic complications. Interestingly, overnutrition-induced hypothalamic inflammation occurs specifically in the ARH, where microglia initiate an inflammatory response by releasing proinflammatory cytokines and chemokines in response to excessive fatty acid flux. Upon more prolonged HFD consumption, astrocytes and perivascular macrophages become involved and sustain hypothalamic inflammation. ARH neurons are victims of hypothalamic inflammation, but they may actively participate in hypothalamic inflammation by sending quiescence or stress signals to surrounding glia. In this mini-review, we describe the current state of knowledge regarding the contributions of neurons and glia, and their interactions, to HFD-induced hypothalamic inflammation.
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http://dx.doi.org/10.14348/molcells.2020.0055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264480PMC
May 2020

Elevated protein synthesis in microglia causes autism-like synaptic and behavioral aberrations.

Nat Commun 2020 04 14;11(1):1797. Epub 2020 Apr 14.

Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL, 33458, USA.

Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD.
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http://dx.doi.org/10.1038/s41467-020-15530-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156673PMC
April 2020

Clinical Impact of Implantable Cardioverter-Defibrillator Therapy and Mortality Prediction Model for Effective Primary Prevention in Korean Patients.

J Korean Med Sci 2020 Mar 9;35(9):e49. Epub 2020 Mar 9.

Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Korea.

Background: Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention.

Methods: Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138).

Results: During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%, = 0.118). However, appropriate ICD therapy rate including shock and anti-tachycardia pacing was significantly higher (primary 18% vs. secondary 34.8%, = 0.001) in the secondary prevention group. Type of prevention and etiology, appropriate and inappropriate ICD shock did not affect all-cause death. High levels of N-terminal pro-B-type natriuretic peptide, New York Heart Association functional class, low levels of estimated glomerular filtration ratio, and body mass index were associated with death before appropriate ICD shock in the primary prevention group. When patients were categorized in 5 risk score groups according to the sum of values defined by each cut-off level, significant differences in death rate before appropriate ICD shock were observed among risk 0 (0%), 1 (3.6%), 2 (3%), 3 (26.5%), and 4 (40%) ( < 0.001).

Conclusion: In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.
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http://dx.doi.org/10.3346/jkms.2020.35.e49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061144PMC
March 2020

Association Between Functional Activity of Mitochondria and Actin Cytoskeleton Instability in Oocytes from Advanced Age Mice.

Reprod Sci 2020 04 5;27(4):1037-1046. Epub 2020 Feb 5.

CHA Fertility Center Seoul Station, CHA University School of Medicine, Seoul, 04637, South Korea.

Mitochondrial dysfunction is strongly associated with the oocyte quality and aging, wherein the aged oocytes are related to the actin cytoskeleton integrity; however, whether this integrity is associated with mitochondrial dysfunction in oocytes from aged mice remains unclear. In the present study, we investigated the relationship between mitochondrial dysfunction and actin cytoskeleton instability in oocytes from the aged mice. We performed comparable analysis of mitochondrial motility between young, 1.5 μM cytochalasin B (CB)-treated young oocytes, and aged oocytes by confocal live imaging. Moreover, we analyzed the relationships between mitochondrial motility and maturation ratios, including ATP production ratio of the young, CB-treated young, and aged oocytes. Actin cytoskeleton instability in the aged oocytes and CB-treated young oocytes led to a significant decrease in the mitochondrial motility and low ATP productive ratios compared to those in the young group. Our data suggest that the actin cytoskeleton instability is presumably the primary cause for the loss of mitochondrial function in the aged murine oocytes.
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http://dx.doi.org/10.1007/s43032-020-00145-2DOI Listing
April 2020

Effect of Operator Volume on In-Hospital Outcomes Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction: Based on the 2014 Cohort of Korean Percutaneous Coronary Intervention (K-PCI) Registry.

Korean Circ J 2020 Feb 18;50(2):133-144. Epub 2019 Nov 18.

Division of Cardiovascular, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea.

Background And Objectives: The relationship between operator volume and outcomes of percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) has not been fully investigated. We aimed to investigate the relationship between operator PCI volume and in-hospital outcomes after primary PCI for STEMI.

Methods: Among the total of 44,967 consecutive cases of PCI enrolled in the Korean nationwide, retrospective registry (K-PCI registry), 8,282 patients treated with PCI for STEMI by 373 operators were analyzed. PCI volumes above the 75th percentile (>30 cases/year), between the 75th and 25th percentile (10-30 cases/year), and below the 25th percentile (<10 cases/year) were defined as high, moderate, and low-volume operators, respectively. In-hospital outcomes including mortality, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and urgent repeat PCI were analyzed.

Results: The average number of primary PCI cases performed by 373 operators was 22.2 in a year. In-hospital mortality after PCI for STEMI was 571 cases (6.9%). In-hospital outcomes by operator volume showed no significant differences in the death rate, cardiac death, non-fatal MI, and stent thrombosis. However, the rate of urgent repeat PCI tended to be lower in the high-volume operator (0.6%) than in the moderate-(0.7%)/low-(1.5%) volume operator groups (p=0.095). The adjusted odds ratios for adverse in-hospital outcomes were similar in the 3 groups. Multivariate analysis also showed that operator volume was not a predictor for adverse in-hospital outcomes.

Conclusions: In-hospital outcomes after primary PCI for STEMI were not associated with operator volume in the K-PCI registry.
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http://dx.doi.org/10.4070/kcj.2019.0206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974659PMC
February 2020

Coronary artery aneurysm in Kawasaki disease: from multimodality imaging.

Coron Artery Dis 2020 03;31(2):193-194

Division of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea.

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http://dx.doi.org/10.1097/MCA.0000000000000792DOI Listing
March 2020

Cellular source of hypothalamic macrophage accumulation in diet-induced obesity.

J Neuroinflammation 2019 Nov 14;16(1):221. Epub 2019 Nov 14.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: Obese mice on a high-fat diet (HFD) display signs of inflammation in the hypothalamic arcuate nucleus (ARC), a critical area for controlling systemic energy metabolism. This has been suggested as a key mechanism of obesity-associated hypothalamic dysfunction. We reported earlier that bone marrow-derived macrophages accumulate in the ARC to sustain hypothalamic inflammation upon chronic exposure to an HFD. However, the mechanism underlying hypothalamic macrophage accumulation has remained unclear.

Methods: We investigated whether circulating monocytes or myeloid precursors contribute to hypothalamic macrophage expansion during chronic HFD feeding. To trace circulating myeloid cells, we generated mice that express green fluorescent protein (GFP) in their lysozyme M-expressing myeloid cells (LysM mice). We conducted parabiosis and bone marrow transplantation experiments using these animals. Mice received an HFD for 12 or 30 weeks and were then sacrificed to analyze LysM cells in the hypothalamus. Hypothalamic vascular permeability in the HFD-fed obese mice was also tested by examining the extravascular leakage of Evans blue and fluorescence-labeled albumin. The timing of LysM cell entry to the hypothalamus during development was also evaluated.

Results: Our parabiosis and bone marrow transplantation experiments revealed a significant infiltration of circulating LysM cells into the liver, skeletal muscle, choroid plexus, and leptomeninges but not in the hypothalamic ARC during chronic HFD feeding, despite increased hypothalamic vascular permeability. These results suggested that the recruitment of circulating monocytes is not a major mechanism for maintaining and expanding the hypothalamic macrophage population in diet-induced obesity. We demonstrated instead that LysM cells infiltrate the hypothalamus during its development. LysM cells appeared in the hypothalamic area from the late embryonic period. This cellular pool suddenly increased immediately after birth, peaked at the postnatal second week, and adopted an adult pattern of distribution after weaning.

Conclusions: Bone marrow-derived macrophages mostly populate the hypothalamus in early postnatal life and may maintain their pool without significant recruitment of circulating monocytes throughout life, even under conditions of chronic HFD feeding.
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http://dx.doi.org/10.1186/s12974-019-1607-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857282PMC
November 2019

Purulent pericarditis: subdiaphragmatic suppurative focus.

Yeungnam Univ J Med 2020 Jan 4;37(1):63-66. Epub 2019 Sep 4.

Division of Cardiology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Purulent pericarditis is defined as a localized pericardial infection with gross pus formation in the pericardial space. Although purulent pericarditis is now rare in the antibiotic era, it may be life-threatening. We describe a rare case of purulent pericarditis that originated from a subdiaphragmatic suppurative focus in an immunocompromised host.
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http://dx.doi.org/10.12701/yujm.2019.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986957PMC
January 2020

Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture.

J Microbiol 2019 Nov 28;57(11):1033-1039. Epub 2019 Oct 28.

Department of Microbiology, Chungbuk National University, Cheongju, 28644, Republic of Korea.

Primary infections with the varicella-zoster virus (VZV) result in varicella, while latent reactivation leads to herpes zoster. Both varicella and zoster can be prevented by live attenuated vaccines. There have been reports suggesting that both clinical VZV strains and those in vaccine preparations are genetically polymorphic, containing mixtures of both wild-type and vaccine-type sequences at certain vaccine-specific sites. In this study, the genetic polymorphism of the VZV genome was examined by analyzing the frequencies of minor alleles at each nucleotide position. Next-generation sequencing of the clinical VZV strain YC02 passaged in an in vitro cell culture was used to identify genetically polymorphic sites (GPS), where the minor allele frequency (MAF) exceeded 5%. The number of GPS increased by 7.3-fold at high passages (p100) when compared to low passages (p17), although the average MAF remained similar. GPS were found in 6 open reading frames (ORFs) in p17, 35, and 54 ORFs in p60 and p100, respectively. GPS were found more frequently in the dispensable gene group than the essential gene group, but the average MAF was greater in the essential gene group. The most common two major/minor base pairs were A/g and T/c. GPS were found in all three passages at 16 positions, all located in the reiterated (R) region. The population diversity as measured by Shannon entropy increased in p60 and p100. However, the entropy remained unchanged in the R regions.
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http://dx.doi.org/10.1007/s12275-019-9429-4DOI Listing
November 2019

Whole Transcriptome Analyses Reveal Differential mRNA and microRNA Expression Profiles in Primary Human Dermal Fibroblasts Infected with Clinical or Vaccine Strains of Varicella Zoster Virus.

Pathogens 2019 Oct 10;8(4). Epub 2019 Oct 10.

Bk21 PLUS Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea.

Licensed live attenuated vaccines have been developed to prevent varicella zoster virus (VZV) infection, which causes chickenpox and shingles. The genomic sequences of both clinical- and vaccine-derived VZV strains have been analyzed previously. To further characterize the molecular signatures and complexity of wildtype (clinical) versus attenuated (vaccine-derived) VZV-mediated host cellular responses, we performed high-throughput next generation sequencing to quantify and compare the expression patterns of mRNAs and microRNAs (miRNAs) in primary human dermal fibroblasts (HDFs) infected with wildtype (YC01 low passage) and attenuated (YC01 high passage, SuduVax, and VarilRix) VZV strains. 3D-multidimensional scaling of the differentially expressed genes demonstrated the distinct grouping of wildtype and attenuated strains. In particular, we observed that HDFs infected with attenuated strains had more differentially expressed genes (DEGs) involved in the retinoic-acid inducible gene-I-like receptor and interferon-mediated signaling pathways compared with wildtype strains. Additionally, miRNA expression patterns were profiled following the infection of HDFs with VZV. Small RNA sequencing identified that several miRNAs were upregulated, including miR-146a-5p, which has been associated with other herpesvirus infections, whereas let-7a-3p was downregulated in both wildtype and attenuated VZV-infected cells. This study identified genes and miRNAs that may be essential in VZV pathogenesis.
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http://dx.doi.org/10.3390/pathogens8040183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963325PMC
October 2019

Impact of Oxidative Stress on Long-Term Heart Rate Variability: Linear Versus Non-Linear Heart Rate Dynamics.

Heart Lung Circ 2020 Aug 10;29(8):1164-1173. Epub 2019 Aug 10.

Division of Cardiology, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea. Electronic address:

Background: Heart rate variability (HRV) is a widely used non-invasive and quantitative marker of cardiac autonomic control. Elevated oxidative stress (OS) and reduced HRV have been proven in specific disease subsets. However, the impact of OS on the long-term heart rate dynamics of both conventional linear and non-linear origin in the general population is not known.

Methods: The 24-hour ambulatory electrocardiogram recordings and plasma 8-iso-prostaglandin F2α (8-iso-PGF2α) levels as an OS marker were acquired simultaneously in 71 consecutive patients. The conventional time and frequency domain HRV parameters and non-linear parameters were measured.

Results: The 8-iso-PGF2α is a significant determinant of most long-term conventional time and frequency domain HRV parameters and standard deviation (SD1, perpendicular to the line of identity; SD2, along the line of identity) descriptors from Poincaré plot analysis, but not of non-linear complexity and fractal parameters. Patients with a high OS burden had lower absolute low-frequency and high-frequency powers during both the night and morning periods, with a significant decrease in high-frequency power in the morning.

Conclusions: Oxidative stress is one of the significant determinants of the HRV. The severity of OS is reflected in the conventional time and frequency domain HRV parameters, but not in the non-linear measurements.
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http://dx.doi.org/10.1016/j.hlc.2019.06.726DOI Listing
August 2020
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