Publications by authors named "Ji-Young Kim"

1,059 Publications

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Association between ectopic pancreatic and hepatic fat and metabolic risk factors in children with non-alcoholic fatty liver disease.

Pediatr Obes 2021 May 4:e12793. Epub 2021 May 4.

Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea.

Background: Few studies have reported an association between ectopic pancreatic and hepatic fat and metabolic factors in children with non-alcoholic fatty liver disease (NAFLD).

Objectives: We investigated this association and also the factors associated with pancreatic and hepatic fat deposition in children with NAFLD.

Methods: This cross-sectional study investigated 65 children with NAFLD (49 boys, 13.0 ± 3.2 years, mean body mass index z-score 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging-based proton density fat fraction, as well as anthropometry, laboratory tests, body composition analysis, and hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) measurements.

Results: HFF and PFF were 4.2%-49.9% (median 24.3) and 0.4%-26.9% (median 3.8), respectively. HFF was not significantly correlated with PFF. HFF was correlated with total body fat% (r = 0.329, p = 0.010) and γ-glutamyl transpeptidase (GGT) (r = 0.260, p = 0.040), while PFF was correlated with the diastolic blood pressure (r = 0.253, p = 0.045), GGT (r = 0.335, p = 0.007) and fasting plasma glucose (r = 0.417, p = 0.001). Multiple linear regression analysis showed that HFF was significantly associated with sex, age, body fat% and GGT, whereas PFF was associated with hypertension and fasting plasma glucose levels but not insulin resistance.

Conclusions: HFF was associated with sex, age and body fat in children with NAFLD, while PFF was associated with hypertension and increased fasting plasma glucose, which suggests that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD.
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http://dx.doi.org/10.1111/ijpo.12793DOI Listing
May 2021

Marliolide Derivative Induces Melanosome Degradation via Nrf2/p62-Mediated Autophagy.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

STEMORE Co. Ltd., Incheon 21983, Korea.

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is linked to autophagy regulation and melanogenesis regulation, is activated by marliolide. In this study, we investigated the effect of a marliolide derivative on melanosome degradation through the autophagy pathway. The effect of the marliolide derivative on melanosome degradation was investigated in α-melanocyte stimulating hormone (α-MSH)-treated melanocytes, melanosome-incorporated keratinocyte, and ultraviolet (UV)B-exposed HRM-2 mice (melanin-possessing hairless mice). The marliolide derivative, 5-methyl-3-tetradecylidene-dihydro-furan-2-one (DMF02), decreased melanin pigmentation by melanosome degradation in α-MSH-treated melanocytes and melanosome-incorporated keratinocytes, evidenced by premelanosome protein (PMEL) expression, but did not affect melanogenesis-associated proteins. The UVB-induced hyperpigmentation in HRM-2 mice was also reduced by a topical application of DMF02. DMF02 activated Nrf2 and induced autophagy in vivo, evidenced by decreased PMEL in microtubule-associated proteins 1A/1B light chain 3B (LC3)-II-expressed areas. DMF02 also induced melanosome degradation via autophagy in vitro, and DMF02-induced melanosome degradation was recovered by chloroquine (CQ), which is a lysosomal inhibitor. In addition, Nrf2 silencing by siRNA attenuated the DMF02-induced melanosome degradation via the suppression of p62. DMF02 induced melanosome degradation in melanocytes and keratinocytes by regulating autophagy via Nrf2-p62 activation. Therefore, Nrf2 activator could be a promising therapeutic agent for reducing hyperpigmentation.
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http://dx.doi.org/10.3390/ijms22083995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070456PMC
April 2021

The Effect of Intraoperative Fluid Management According to Stroke Volume Variation on Postoperative Bowel Function Recovery in Colorectal Cancer Surgery.

J Clin Med 2021 Apr 25;10(9). Epub 2021 Apr 25.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Stroke volume variation (SVV) has been used to predict fluid responsiveness; however, it remains unclear whether goal-directed fluid therapy using SVV contributes to bowel function recovery in abdominal surgery. This prospective randomized controlled trial aimed to compare bowel movement recovery in patients undergoing colon resection surgery between groups using traditional or SVV-based methods for intravenous fluid management. We collected data between March 2015 and July 2017. Bowel function recovery was analyzed based on the gas-passing time, sips of water time, and soft diet (SD) time. Finally, we analyzed data from 60 patients. There was no significant between-group difference in the patients' characteristics. Compared with the control group ( = 30), the SVV group ( = 30) had a significantly higher colloid volume and lower crystalloid volume. Moreover, the gas-passing time (77.8 vs. 85.3 h, = 0.034) and SD time (67.6 vs. 85.1 h, < 0.001) were significantly faster in the SVV group than in the control group. Compared with the control group, the SVV group showed significantly lower scores of pain on a numeric rating scale and morphine equivalent doses during post-anesthetic care, at 24 postoperative hours, and at 48 postoperative hours. Our findings suggested that, compared with the control group, the SVV group showed a faster postoperative SD time, reduced acute postoperative pain intensity, and lower rescue analgesics. Therefore, SVV-based optimal fluid management is expected to potentially contribute to postoperative bowel function recovery in patients undergoing colon resection surgery.
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http://dx.doi.org/10.3390/jcm10091857DOI Listing
April 2021

Factors Associated with Medication Beliefs in Patients with Parkinson's Disease: A Cross-Sectional Study.

J Mov Disord 2021 May 3. Epub 2021 May 3.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: Medication beliefs are a significant determinant of medication adherence in chronic illness. This study aimed to identify demographic, clinical, and medication-related factors associated with medication beliefs in patients with Parkinson's disease (PD).

Methods: We used a descriptive cross-sectional design with a convenience sample of 173 PD patients who had been taking antiparkinson drugs for more than one year.

Results: The subjects who believed PD medication was more necessary had more severe illness, younger age of onset, longer illness duration, and longer duration of levodopa therapy. They had higher levels of non-motor symptoms and depression, number of medication uses, number of drugs, and levodopa equivalent dose, and they reported fluctuation of motor symptoms and dyskinesia. The subjects who used catechol-O-methyltransferase (COMT) inhibitors, dopamine agonists, amantadine, and monoamine oxidase-B (MAO-B) inhibitors had significantly higher necessity scores than those who did not use them. The subjects who had higher concerns about PD medications had higher levels of non-motor symptoms and depression. The subjects using amantadine and anticholinergics had significantly higher concern scores than those who did not use them. Positive necessity-concerns differentials were associated with severe illness, the presence of motor fluctuation and dyskinesia, and the use of COMT inhibitors. Based on stepwise multiple regression, the most significant factors influencing necessity beliefs were severe illness, followed by depression and motor fluctuation.

Conclusion: Severe illness, higher levels of depression, and motor fluctuation are independent factors influencing patients' beliefs regarding medication necessity. Therefore, these characteristics should be considered in medication belief assessment and interventions for PD patients.
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http://dx.doi.org/10.14802/jmd.20147DOI Listing
May 2021

PERK mediates oxidative stress and adipogenesis in Graves' orbitopathy pathogenesis.

J Mol Endocrinol 2021 Apr 1. Epub 2021 Apr 1.

J Yoon, Ophthalmology, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of).

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves' orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress related genes in orbital tissue harvested from individuals with or without GO was studied using real-time polymerase chain reaction. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through western blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein(CHOP)mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.
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http://dx.doi.org/10.1530/JME-21-0057DOI Listing
April 2021

A retrospective multicenter study of quantitative bone SPECT/CT to predict the surgical removal of the accessory navicular bone.

Nucl Med Commun 2021 Apr 16. Epub 2021 Apr 16.

Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam-si Department of Nuclear Medicine, Hanyang University Guri Hospital, Guri-si, Gyeonggi-do Department of Nuclear Medicine, Soonchunhyang University Seoul Hospital, Seoul Department of Nuclear Medicine, Korea University Ansan Hospital, Ansan Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea.

Objective: The maximum standardized uptake value (SUVmax) in single-photon emission computed tomography/computed tomography (SPECT/CT) can help quantify disease activity of the accessory navicular bone (ANB). In this multicenter quantitative bone SPECT/CT study, we investigated whether SUVmax was correlated with ANB severity, thereby allowing prediction of surgical resection for ANB treatment.

Methods: Two-hundred forty-six patients (men:women = 135:111, mean age = 39.3 years), who had undergone quantitative Tc-99m diphosphonate SPECT/CT of the feet, were recruited from four hospitals. SUVmax was measured using vendor-provided quantitation software. The SUVmax values were compared in relation to ANB type (type 1 = 62, type 2 = 136 and type 3 = 14), presence of pain and surgical treatment.

Results: SUVmax (mean ± SD) was the highest in type 2 ANB (4.41 ± 5.2; P = 0.0101). The 17 resected ANBs showed greater SUVmax (8.27 ± 5.23; P < 0.0001) than the 141 asymptomatic ANBs (2.30 ± 1.68) or the 54 symptomatic ANBs without surgery (6.15 ± 4.40). Since surgery is exclusively indicated for ANB type 2, surgical resection was investigated only in these cases. In univariate analysis, young age and SUVmax were significantly associated with surgical treatment, but only SUVmax was a significant predictor of surgery in multivariate analysis (P < 0.0001). Type 2 ANBs were treated by surgery in 32.5% (13/40) of the cases when SUVmax was ≥5, and in only 1.35% (1/74) of the cases when SUVmax was <5 (P < 0.0001).

Conclusion: ANB disease activity and excision were strongly associated with the SUVmax derived from quantitative bone SPECT/CT. Our study suggests an absolute SUVmax cutoff for ultimate ANB surgical treatment, but additional prospective studies are required to validate this finding.
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http://dx.doi.org/10.1097/MNM.0000000000001433DOI Listing
April 2021

Development of a highly active FeNC catalyst with the preferential formation of atomic iron sites for oxygen reduction in alkaline and acidic electrolytes.

J Colloid Interface Sci 2021 Aug 19;596:148-157. Epub 2021 Mar 19.

Department of Energy and Materials Engineering, Dongguk University, Seoul 04620, Republic of Korea. Electronic address:

Nitrogen-doped porous carbons containing atomically dispersed iron are prime candidates for substituting platinum-based catalysts for oxygen reduction reaction (ORR) in fuel cells. These carbon catalysts are classically synthesizedviacomplicated routes involving multiple heat-treatment steps to form the desired Fe-N sites. We herein developed a highly active FeNC catalyst comprising of exclusive Fe-N sites by a simplified solid-state synthesis protocol involving only a single heat-treatment. Imidazole is pyrolyzed in the presence of an inorganic salt-melt resulting in highly porous carbon sheets decorated with abundant Fe-N centers, which yielded a high density of electrochemically accessible active sites (1.36 × 10 sites g) as determined by the in situ nitrite stripping technique. The optimized catalyst delivered a remarkable ORR activity with a half-wave potential (E) of 0.905 V in alkaline electrolyte surpassing the benchmark Pt catalyst by 55 mV. In acidic electrolyte, an E of 0.760 V is achieved at a low loading level (0.29 mg cm). In PEMFC tests, a current density of 2.3 mA cm is achieved at 0.90 V under H-O conditions, reflecting high kinetic activity of the optimized catalyst.
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http://dx.doi.org/10.1016/j.jcis.2021.03.081DOI Listing
August 2021

Mercury Chloride but Not Lead Acetate Causes Apoptotic Cell Death in Human Lung Fibroblast MRC5 Cells via Regulation of Cell Cycle Progression.

Int J Mol Sci 2021 Mar 2;22(5). Epub 2021 Mar 2.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Heavy metals are important for various biological systems, but, in excess, they pose a serious risk to human health. Heavy metals are commonly used in consumer and industrial products. Despite the increasing evidence on the adverse effects of heavy metals, the detailed mechanisms underlying their action on lung cancer progression are still poorly understood. In the present study, we investigated whether heavy metals (mercury chloride and lead acetate) affect cell viability, cell cycle, and apoptotic cell death in human lung fibroblast MRC5 cells. The results showed that mercury chloride arrested the sub-G and G/M phases by inducing cyclin B1 expression. In addition, the exposure to mercury chloride increased apoptosis through the activation of caspase-3. However, lead had no cytotoxic effects on human lung fibroblast MRC5 cells at low concentration. These findings demonstrated that mercury chloride affects the cytotoxicity of MRC5 cells by increasing cell cycle progression and apoptotic cell death.
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http://dx.doi.org/10.3390/ijms22052494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958599PMC
March 2021

Factors Influencing Quality of Life in Early Postpartum Women.

Int J Environ Res Public Health 2021 03 14;18(6). Epub 2021 Mar 14.

College of Nursing, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju, Jeollabuk do 54896, Korea.

Postpartum women experience various changes in their physical and psychological health and in their relationships with their spouse and newborn. This study aimed to identify and evaluate the factors that affect the quality of life (QoL) of women within six weeks after childbirth. A prospective, cross-sectional correlational study was used. A convenience sample of 179 postpartum women was recruited from four postpartum care centers in South Korea. Participants completed structured questionnaires on postpartum fatigue, postpartum depression, marital intimacy, breastfeeding adaptation, and quality of life. Marital intimacy (β = 0.466, < 0.001) was the most influencing factor on the QoL of women during the postpartum period. In descending order, postpartum fatigue (β = -0.192, = 0.001), postpartum depression (β = -0.190, = 0.001), breastfeeding adaptation (β = 0.163, = 0.002), and occupation (β = 0.163, = 0.004) all had a significant influence on QoL (F = 32.09, < 0.001), and the overall explanatory power was 63.6%. It is necessary to assess and consider the physical, psychological, relational, and demographic factors of women during the early postpartum period. Comprehensive interventions need to be developed to improve the QoL of women during the postpartum period.
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http://dx.doi.org/10.3390/ijerph18062988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000893PMC
March 2021

MRI risk factors for development of avascular necrosis after closed reduction of developmental dysplasia of the hip: Predictive value of contrast-enhanced MRI.

PLoS One 2021 18;16(3):e0248701. Epub 2021 Mar 18.

Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: The purpose of this study was to identify imaging risk factors on contrast-enhanced hip MRI after closed reduction of developmental dysplasia of the hip (DDH) that could predict future development of avascular necrosis (AVN) of the femoral head.

Materials And Methods: Fifty-eight infants (F: M = 53: 5, aged 3-18 months) who underwent immediate postoperative contrast-enhanced hip MRI after closed reduction of DDH were included in this study. Quality of reduction (concentric vs eccentric reduction with or without obstacles), abduction angle of the hip, presence of ossific nucleus, and pattern of contrast enhancement of the femoral head were retrospectively evaluated on MRI. Interobserver agreement of contrast enhancement pattern on MRI were evaluated by two radiologists. Development of AVN was determined through radiographic findings at 1 year after reduction.

Results: AVN of the femoral head developed in 13 (22%) of 58 patients. Excessive abduction of the hip joint (OR 4.65, [95% CI 1.20, 18.06] and global decreased enhancement of the femoral head (OR 71.66, [95% CI 10.54, 487.31]) exhibited statistically significant differences between the AVN and non-AVN groups (P < 0.05). Eccentric reduction (P = 0.320) did not show statistically significant difference between two groups and invisible ossific nucleus (P = 0.05) showed borderline significance. Multi-variable logistic regression indicated that global decreased enhancement of the femoral head was a significant risk factor of AVN (OR 27.92, 95% CI [4.17, 350.18]) (P = 0.0031). Interobserver agreement of contrast enhancement pattern analysis and diagnosis of AVN were good (0.66, 95% CI [0.52, 0.80]).

Conclusion: Contrast-enhanced hip MRI provides accurate anatomical assessment of the hip after closed reduction of DDH. Global decreased enhancement of the femoral head could be used as a good predictor for future development of AVN after closed reduction of DDH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248701PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971487PMC
March 2021

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

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

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

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

-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis.

Front Immunol 2021 25;12:615369. Epub 2021 Feb 25.

Department of Parasitology and Tropical Medicine, Chonnam National University Medical School, Gwangju, South Korea.

Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of -derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF- , IL-17A, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with CSp or vehicles. Inflammation and new bone formation were evaluated using immunohistochemistry, positron emission tomography (PET), and micro-computed tomography (CT). Treatment with CSp resulted in no reduced cell viability of PBMCs or SFMCs until 24 h. In experiments culturing PBMCs and SFMCs, the frequencies of IFN- and IL-17A producing cells were significantly reduced after CSp treatment. In the SKG mouse model, CSp treatment significantly suppressed arthritis, enthesitis, and enteritis. Micro-CT analysis of hind paw revealed reduced new bone formation in CSp-treated mice than in vehicle-treated mice. We provide the first evidence demonstrating that CSp can ameliorate clinical signs and cytokine derangements in AS. In addition, such CSp treatment could reduce the new bone formation of AS.
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http://dx.doi.org/10.3389/fimmu.2021.615369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947613PMC
February 2021

Aromatic and Aliphatic Apiuronides from the Bark of .

J Nat Prod 2021 03 8;84(3):553-561. Epub 2021 Mar 8.

Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Presl (Cinnamon) has been widely cultivated in the tropical or subtropical areas, such as Yunnan, Fujian, Guandong, and Hainan in China, as well as India, Vietnam, Thailand, and Malaysia. Four new glycosides bearing apiuronic acid (, , , and ) and their sodium or potassium salts (, , and ), together with 31 known compounds, were isolated from a hot water extract of the bark of via repeated chromatography. The structures of the new compounds (-) were determined by NMR, IR, MS, and ICP-AES data and by acid hydrolysis and sugar analysis. This is the first report of the presence of apiuronic acid glycosides. Some of the isolates were evaluated for their analgesic effects on a neuropathic pain animal model induced by paclitaxel. Cinnzeylanol (), cinnacaside (), kelampayoside A (), and syringaresinol () showed analgesic effects against paclitaxel-induced cold allodynia.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01062DOI Listing
March 2021

Transcriptome Analysis Reveals HgCl Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

Int J Mol Sci 2021 Feb 18;22(4). Epub 2021 Feb 18.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl treatment causes inhibition of cell growth via cell cycle arrest at G/G- and S-phase. In addition, HgCl induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl treatment. Altogether, these data show that HgCl induces apoptotic cell death through the dysfunction of mitochondria.
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http://dx.doi.org/10.3390/ijms22042006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922270PMC
February 2021

Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.

Genes (Basel) 2021 Feb 11;12(2). Epub 2021 Feb 11.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Bisphenol A (BPA) is a xenoestrogen chemical commonly used to manufacture polycarbonate plastics and epoxy resin and might affect various human organs. However, the cellular effects of BPA on the eyes have not been widely investigated. This study aimed to investigate the cellular cytotoxicity by BPA exposure on human retinoblastoma cells. BPA did not show cytotoxic effects, such as apoptosis, alterations to cell viability and cell cycle regulation. Comparative analysis of the transcriptome and proteome profiles were investigated after long-term exposure of Y79 cells to low doses of BPA. Transcriptome analysis using RNA-seq revealed that mRNA expression of the post-transcriptional regulation-associated gene sets was significantly upregulated in the BPA-treated group. Cell cycle regulation-associated gene sets were significantly downregulated by exposure to BPA. Interestingly, RNA-seq analysis at the transcript level indicated that alternative splicing events, particularly retained introns, were noticeably altered by low-dose BPA treatment. Additionally, proteome profiling using MALDI-TOF-MS identified a total of nine differentially expressed proteins. These results suggest that alternative splicing events and altered gene/protein expression patterns are critical phenomena affected by long-term low-dose BPA exposure. This represents a novel marker for the detection of various diseases associated with environmental pollutants such as BPA.
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http://dx.doi.org/10.3390/genes12020264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918513PMC
February 2021

Factors Predicting the Success of Adhesiolysis Using a Steerable Catheter in Lumbar Failed Back Surgery Syndrome: A Retrospective Study.

J Clin Med 2021 Feb 26;10(5). Epub 2021 Feb 26.

Department of Anesthesiology and Pain Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea.

Failed back surgery syndrome (FBSS) is a commonly encountered disease after lumbar surgery. There are many cases where it is difficult to choose a treatment because no specific cause can be found. Nevertheless, according to recent reports, adhesiolysis has shown reasonable evidence. However, considering its poor cost-effectiveness, adhesiolysis cannot be used as the first line of treatment. FBSS patients often suffer from chronic pain; accordingly, they become frustrated when this treatment produces a poor response. Therefore, before the procedure, the target group must be selected carefully. We sought to identify the pre-procedure factors predicting the effect of adhesiolysis in FBSS. A total of 150 patients were evaluated and analyzed retrospectively. Of these 150 patients, 69 were classified as responders three months after the procedure (46%). The outer diameter of the catheter during the procedure and grade of foraminal stenosis were correlated with the procedure effect. In conclusion, of the 2.1 mm diameter of the catheter, 1.7 mm of it was used during the procedure, and the milder the foraminal stenosis, the greater the pain reduction effect was three months after the procedure.
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http://dx.doi.org/10.3390/jcm10050913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956797PMC
February 2021

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models.

EMBO Mol Med 2021 Apr 1;13(4):e13076. Epub 2021 Mar 1.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.

Astrocytes and microglia are brain-resident glia that can establish harmful inflammatory environments in disease contexts and thereby contribute to the progression of neuronal loss in neurodegenerative disorders. Correcting the diseased properties of glia is therefore an appealing strategy for treating brain diseases. Previous studies have shown that serum/ glucocorticoid related kinase 1 (SGK1) is upregulated in the brains of patients with various neurodegenerative disorders, suggesting its involvement in the pathogenesis of those diseases. In this study, we show that inhibiting glial SGK1 corrects the pro-inflammatory properties of glia by suppressing the intracellular NFκB-, NLRP3-inflammasome-, and CGAS-STING-mediated inflammatory pathways. Furthermore, SGK1 inhibition potentiated glial activity to scavenge glutamate toxicity and prevented glial cell senescence and mitochondrial damage, which have recently been reported as critical pathologic features of and therapeutic targets in Parkinson disease (PD) and Alzheimer disease (AD). Along with those anti-inflammatory/neurotrophic functions, silencing and pharmacological inhibition of SGK1 protected midbrain dopamine neurons from degeneration and cured pathologic synuclein alpha (SNCA) aggregation and PD-associated behavioral deficits in multiple in vitro and in vivo PD models. Collectively, these findings suggest that SGK1 inhibition could be a useful strategy for treating PD and other neurodegenerative disorders that share the common pathology of glia-mediated neuroinflammation.
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http://dx.doi.org/10.15252/emmm.202013076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033538PMC
April 2021

Cardiac autonomic dysfunction is associated with hypothalamic damage in patients with childhood-onset craniopharyngioma.

PLoS One 2021 16;16(2):e0246789. Epub 2021 Feb 16.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Autonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma.

Methods: A cross-sectional study of 48 patients (28 males, 10-30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured.

Results: Patients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity.

Conclusions: The reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246789PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886170PMC
February 2021

Feasibility of Coronary Artery Calcium Scoring on Dual-Energy Chest Computed Tomography: A Prospective Comparison with Electrocardiogram-Gated Calcium Score Computed Tomography.

J Clin Med 2021 Feb 8;10(4). Epub 2021 Feb 8.

Department of Radiology and The Research Institute of Radiological Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea.

: This study aimed to evaluate the feasibility of assessment using the coronary artery calcium score (CACS) in dual-energy chest computed tomography (CT). : We prospectively enrolled 30 patients (19 male, 11 female; mean age, 63.73 ± 9.40 years) who clinically required contrast-enhanced chest CT. The patients underwent electrocardiogram-gated cardiac calcium-scoring CT with a slice thickness of 2.5 mm followed by a sequentially non-gated contrast-enhanced dual-energy chest CT using 140/80 fast kVp switching technology with slice thicknesses of 1.25 mm and 2.5 mm. Virtual unenhanced (VUE) images were then reconstructed from the dual-energy CT using the material suppressed iodine (MSI) technique. : The mean heart rates were 63.33 ± 12.01 beats per minute. The mean CACS on the coronary calcium-scoring CT was 361.1 ± 435.5, and CACSs of the VUE images were 76.8 ± 128.6 (2.5 mm slice) and 108.7 ± 165.1 (1.25 mm slice). The correlation coefficients of CACS between the coronary calcium-scoring CT with the VUE 2.5 mm and 1.25 mm images were 0.888 and 0.904, respectively. The inter-observer agreements for the calcium score measurement between the calcium-scoring CT, VUE 2.5 mm, and VUE 1.25 mm were 1.000, 0.999, and 1.000, respectively. : In conclusion, assessment of CACS using dual-energy chest CT might be feasible when using MSI virtual unenhanced dual-energy chest CT images with a slice thickness of 1.25 mm.
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http://dx.doi.org/10.3390/jcm10040653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915048PMC
February 2021

SRF is a nonhistone methylation target of KDM2B and SET7 in the regulation of skeletal muscle differentiation.

Exp Mol Med 2021 Feb 9;53(2):250-263. Epub 2021 Feb 9.

Department of Pharmacology, Chonnam National University Medical School, Hwasun, Republic of Korea.

The demethylation of histone lysine residues, one of the most important modifications in transcriptional regulation, is associated with various physiological states. KDM2B is a demethylase of histones H3K4, H3K36, and H3K79 and is associated with the repression of transcription. Here, we present a novel mechanism by which KDM2B demethylates serum response factor (SRF) K165 to negatively regulate muscle differentiation, which is counteracted by the histone methyltransferase SET7. We show that KDM2B inhibited skeletal muscle differentiation by inhibiting the transcription of SRF-dependent genes. Both KDM2B and SET7 regulated the balance of SRF K165 methylation. SRF K165 methylation was required for the transcriptional activation of SRF and for the promoter occupancy of SRF-dependent genes. SET7 inhibitors blocked muscle cell differentiation. Taken together, these data indicate that SRF is a nonhistone target of KDM2B and that the methylation balance of SRF as maintained by KDM2B and SET7 plays an important role in muscle cell differentiation.
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http://dx.doi.org/10.1038/s12276-021-00564-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080764PMC
February 2021

Equal Ratio Ventilation Reduces Blood Loss During Posterior Lumbar Interbody Fusion Surgery.

Spine (Phila Pa 1976) 2021 Jan 22. Epub 2021 Jan 22.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Study Design: A prospective randomized double-blinded study.

Objective: The aim of this study was to compare the effect of two different ventilator modes (inspiratory to expiratory ratio (I:E ratio) of 1:1 and 1:2) on intraoperative surgical bleeding in patients undergoing posterior lumbar interbody fusion (PLIF) surgery.

Summary Of Background Data: During PLIF surgery, a considerable amount of blood loss is anticipated. In the prone position, engorgement of the vertebral vein increases surgical bleeding. We hypothesized that equal ratio ventilation (ERV) with I:E ratio of 1:1 would lower peak inspiratory pressure (PIP) in the prone position and consequentially decrease surgical bleeding.

Methods: Twenty-eight patients were randomly assigned to receive either ERV (ERV group, n = 14) or conventional ventilation with I:E ratio of 1:2 (control group, n = 14). Hemodynamic and respiratory parameters were measured at 5 min after anesthesia induction, at 5 min after the prone position, at the time of skin closure, and at 5 min after turning to the supine position.

Results: The amount of intraoperative surgical bleeding in the ERV group was significantly less than that in the control group (975.7 ± 349.9 mL vs. 1757.1 ± 1172.7 mL, P = 0.03). Among other hemodynamic and respiratory parameters, PIP, plateau inspiratory pressure (Pplat) were significantly lower and dynamic lung compliance (Cdyn) was significantly higher in the ERV group than those of the control group throughout the study period, respectively (all P < 0.05).

Conclusion: Compared to conventional ratio ventilation, ERV provided lower PIP and reduced intraoperative surgical blood loss in patients undergoing PLIF surgery.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003957DOI Listing
January 2021

MiR-144-3p is associated with pathological inflammation in patients infected with Mycobacteroides abscessus.

Exp Mol Med 2021 Jan 20;53(1):136-149. Epub 2021 Jan 20.

Department of Microbiology, Chungnam National University School of Medicine, Daejeon, 35015, Korea.

Infection with rapidly growing nontuberculous mycobacteria is emerging as a global health issue; however, key host factors remain elusive. Here, we investigated the characteristic immune profiles of peripheral blood mononuclear cells (PBMCs) from patients infected with Mycobacteroides abscessus subsp. abscessus (Mabc) and M. abscessus subsp. massiliense (Mmass). Using an integrated analysis of global mRNA and microRNA expression profiles, we found that several inflammatory cytokines/chemokines [interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand 2, and C-C motif chemokine ligand 2] and miR-144-3p were significantly upregulated in PBMCs from patients compared with those from healthy controls (HCs). Notably, there was a strong correlation between the expression levels of miR-144-3p and proinflammatory cytokines/chemokines. Similarly, upregulated expression of miR-144-3p and proinflammatory cytokines/chemokines was found in macrophages and lungs from mice after infection with Mabc and Mmass. We showed that the expression of negative regulators of inflammation (SARM1 and TNIP3) was significantly downregulated in PBMCs from the patients, although they were not putative targets of miR-144-3p. Furthermore, overexpression of miR-144-3p led to a marked increase in proinflammatory cytokines/chemokines and promoted bacterial growth in macrophages. Together, our results highlight the importance of miR-144-3p linking to pathological inflammation during M. abscessus infection.
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http://dx.doi.org/10.1038/s12276-020-00552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080579PMC
January 2021

Analysis of Histology, Mechanics, and Safety of Radiation-free Pre-hydrated Human Acellular Dermal Matrix.

J Breast Cancer 2020 Dec 7;23(6):635-646. Epub 2020 Dec 7.

Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Korea.

Purpose: Acellular dermal matrix (ADM) supports tissue expanders or implants in implant-based breast reconstruction. The characteristics of ADM tissue are defined by the manufacturing procedure, such as decellularization, preservation, and sterilization, and are directly related to clinical outcomes. This study aimed to compare the properties of a new pre-hydrated-ADM (H-ADM-low) obtained using a decellularization reagent reduction process with a low concentration of detergent with those of radiation-sterilized H-ADM and freeze-dried ADM (FD-ADM).

Methods: ADMs were evaluated in terms of structure, mechanical quality, and cytotoxicity using histochemical staining, tensile strength testing, and cell viability analysis.

Results: The tissue structure of H-ADM-low (CGDERM ONE-STEP) was similar to that of native skin despite complete decellularization. By contrast, in FD-ADM, the tissue structure was damaged by the freeze-drying process, and radiation-sterilized H-ADM showed a compact fibrillar arrangement. Furthermore, matrix components such as collagen and elastin were preserved in H-ADM-low, whereas a loss of elastin fibers with fragmented distribution was observed in radiation-sterilized H-ADMs. H-ADM-low's tensile strength (58.84 MPa) was significantly greater than that of FD-ADM (38.60 MPa) and comparable with that of radiation-sterilized H-ADMs. The residual detergent content in H-ADM-low (47.45 mg/L) was 2.67-fold lower than that of H-ADM decellularized with a conventional detergent concentration (126.99 mg/mL), and this finding was consistent with the cell viability results (90.7% and 70.7%, respectively), indicating that H-ADM-low has very low cytotoxicity.

Conclusions: H-ADM-low produced through aseptic processes retains the original tissue structure, demonstrates excellent mechanical properties, and does not affect cell viability. Therefore, this newer H-ADM is suitable for use in implant-based breast reconstruction.
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http://dx.doi.org/10.4048/jbc.2020.23.e64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779726PMC
December 2020

Telmisartan Inhibits the NLRP3 Inflammasome by Activating the PI3K Pathway in Neural Stem Cells Injured by Oxygen-Glucose Deprivation.

Mol Neurobiol 2021 Apr 6;58(4):1806-1818. Epub 2021 Jan 6.

Department of Neurology, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri, 11923, South Korea.

Angiotensin II receptor blockers (ARBs) have been shown to exert neuroprotective effects by suppressing inflammatory and apoptotic responses. In the present study, the effects of the ARB telmisartan on the NLRP3 inflammasome induced by oxygen-glucose deprivation (OGD) in neural stem cells (NSCs) were investigated, as well as their possible association with the activation of the PI3K pathway. Cultured NSCs were treated with different concentrations of telmisartan and subjected to various durations of OGD. Cell counting, lactate dehydrogenase, bromodeoxyuridine, and colony-forming unit assays were performed to measure cell viability and proliferation. In addition, the activity of intracellular signaling pathways associated with the PI3K pathway and NLRP3 inflammasome was evaluated. Telmisartan alone did not affect NSCs up to a concentration of 10 μM under normal conditions but showed toxicity at a concentration of 100 μM. Moreover, OGD reduced the viability of NSCs in a time-dependent manner. Nevertheless, treatment with telmisartan increased the viability and proliferation of OGD-injured NSCs. Furthermore, telmisartan promoted the expression of survival-related proteins and mRNA while inhibiting the expression of death-related proteins induced by OGD. In particular, telmisartan attenuated OGD-dependent expression of the NLRP3 inflammasome and its related signaling proteins. These beneficial effects of telmisartan were blocked by a PI3K inhibitor. Together, these results indicate that telmisartan attenuated the activation of the NLRP3 inflammasome by triggering the PI3K pathway, thereby contributing to neuroprotection.
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http://dx.doi.org/10.1007/s12035-020-02253-1DOI Listing
April 2021

The durability and effectiveness of sensor-augmented insulin pump therapy in pediatric and young adult patients with type 1 diabetes.

Ann Pediatr Endocrinol Metab 2020 Dec 31;25(4):248-255. Epub 2020 Dec 31.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Purpose: Despite the prevalent use of insulin pump therapy worldwide, few studies have been conducted among young patients with type 1 diabetes (T1D) in Korea. We investigated the durability and effectiveness of insulin pump therapy among Korean pediatric and young adult patients with T1D.

Methods: This study included 54 patients with T1D diagnosed at pediatric ages (range, 1.1-14.1 years) who initiated insulin pump therapy during 2016-2019 at Seoul National University Children's Hospital and Seoul National University Bundang Hospital. Clinical and biochemical data, including anthropometric measurements, insulin dose, and glycated hemoglobin (HbA1c) levels were obtained from T1D diagnosis to last follow-up.

Results: Forty-four patients (81.5%) continued insulin pump therapy with a median pump use duration of 2.9 years (range, 0.2-3.5 years); 10 discontinued the therapy within 12 months (<1 month, n=6; 1-6 months, n=1; and 6-12 months, n=3) due to physical interferences or financial problems. Older age (≥10 years of age) and longer diabetes duration (≥2 years) at the initiation of pump therapy were associated with discontinuation (P<0.05 for both). For patients continuing pump therapy, HbA1c levels significantly decreased after 1 year of therapy (from 8.9% to 8.1%, P<0.001) without changes in the body mass index z-scores or insulin dose. Although 4 patients experienced diabetic ketoacidosis, all recovered without complications.

Conclusion: Insulin pump therapy was effective in improving glycemic control in T1D patients during 12 months of treatment. Early initiation of insulin pump therapy after T1D diagnosis was helpful for continuing therapy.
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http://dx.doi.org/10.6065/apem.2040048.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788343PMC
December 2020

2017 Clinical practice guidelines for dyslipidemia of Korean children and adolescents.

Ann Pediatr Endocrinol Metab 2020 Dec 31;25(4):199-207. Epub 2020 Dec 31.

Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.
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http://dx.doi.org/10.6065/apem.2040198.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788349PMC
December 2020

Emergent Listener Fluency: A Replication.

Anal Verbal Behav 2020 Dec 15;36(2):318-326. Epub 2020 Oct 15.

Department of Health and Behavior Studies, Teachers College, Columbia University, 525 W 120th St., New York, NY 10027 USA.

Fluent listener behavior is a fundamental repertoire that affects the learning and development of speaker repertoires. We used a concurrent multiple-baseline design across 3 preschool-aged participants with disabilities to evaluate the effectiveness of a listener emersion protocol on increasing listener fluency. Prior to intervention, the participants demonstrated difficulty following vocal directions. The dependent variables were the rate per minute of correct and incorrect listener responses to vocal directions. The listener emersion protocol required participants to follow 4 sets of 5 one-step vocal directions. Results of this study indicate that listener fluency improved with an increased rate of correct responses across all 3 participants as a function of the listener emersion protocol.
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http://dx.doi.org/10.1007/s40616-020-00139-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736441PMC
December 2020

High Vulnerability of Oligodendrocytes to Oxidative Stress Induced by Ultrafine Urban Particles.

Antioxidants (Basel) 2020 Dec 22;10(1). Epub 2020 Dec 22.

Department of Anatomy, Chungbuk National University College of Medicine, Cheongju 28644, Korea.

Oligodendrocytes, myelin-forming cells in the brain, are vulnerable to oxidative stress. Recent work indicates that air pollution causes demyelinating diseases such as multiple sclerosis. However, little is known about the mechanism of toxicity of ultrafine particulate matters (PMs) to oligodendrocytes. Here, we aimed to determine whether oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs) are more vulnerable to ultrafine urban PMs (uf-UPs) than other types of brain cells and damage to adult OPCs and mOLs in the mouse brain exposed to uf-UPs. For in vitro experiments, following exposure to various concentrations (2, 20, and 200 μg/mL) of uf-UPs, we measured survival rates, the amount of reactive oxygen species (ROS), and the total antioxidant capacities (TACs) of brain cells isolated from neonatal Sprague-Dawley rats. For animal experiments, after a four-week exposure to a uf-UP suspension (20 μL, 0.4 mg/mL), we enumerated the number of damaged cells and typed damaged cells in the white matter of the cerebellum of uf-UP-exposed mice. MTT assays and Hoechst staining demonstrated that OPCs and mOLs were more vulnerable to uf-UP-induced damage than astrocytes and cortical neurons at 2, 20, and 200 μg/mL of uf-UPs examined in this study ( < 0.05). Damage to OPCs and mOLs depended on uf-UP concentration. DCF assays and DHE staining indicated that the amount of ROS generated in OPCs and mOLs was significantly higher than in other brain cell types ( < 0.05). In contrast, TAC values in OPCs and mOLs were significantly lower than those of other brain cell types ( < 0.05). Fluoro-Jade B (FJB)-positive cells in the cerebellar white matter of the uf-UP-exposed group were significantly greater in number relative to the control group. Double immunofluorescence indicated that FJB-positive cells are NG2-positive adult OPCs and carbon anhydrase II-positive mOLs. Taken together, our findings suggest that oxidative stress induced by uf-UPs in the brain impairs adult OPCs and mOLs, causing demyelination and reducing the capacity for remyelination.
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http://dx.doi.org/10.3390/antiox10010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822157PMC
December 2020

New Eudesmane-Type Sesquiterpene Glycosides from the Leaves of .

Plants (Basel) 2020 Dec 21;9(12). Epub 2020 Dec 21.

Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea.

Four new eudesmane-type sesquiterpenoids, (1,5,6,7,9,10)-1,6,9-trihydroxy-eudesm-3-ene-1,6-di---d-glucopyranoside (), (1,5,6S,7,9,10)-1,6,9,11-tetrahydroxy-eudesm-3-ene-1,6-di---d-glucopyranoside (), (1,5,6,7,9,10)-9--(--coumaroyl)-1,6,9-trihydroxy-eudesm-3-ene-6---d-glucopyranoside (), and (1,5,6,7,9,10)-9--(-feruloyl)-1,6,9-trihydroxy-eudesm-3-ene-6---d-glucopyranoside (), were isolated from a 95% EtOH extract of the leaves of by repeated chromatography. Moreover, three sesquiterpenoids (, , and ) and two caffeoylquinic acids ( and ) having previously known chemical structures were isolated during the isolation procedure. The four new compounds (, , , and ) were elucidated by spectroscopic data (1D- and 2D-NMR, MS, and ECD) interpretation and hydrolysis. Moreover, the absolute configurations of , , and were determined for the first time in this study. The compounds isolated were tested for their viability on nitric oxide (NO) and prostaglandin E (PGE) production on LPS-stimulated RAW 264.7 cells. Among them, only presented weak inhibitory effects on both NO and PGE production.
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http://dx.doi.org/10.3390/plants9121811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766762PMC
December 2020

Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis.

Nature 2021 02 23;590(7847):612-617. Epub 2020 Dec 23.

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

In the adult hippocampus, synapses are constantly formed and eliminated. However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we show that astrocytic phagocytosis is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10-knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function.
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http://dx.doi.org/10.1038/s41586-020-03060-3DOI Listing
February 2021