Publications by authors named "Sang-Min Kim"

222 Publications

REM Sleep Deprivation Impairs Learning and Memory by Decreasing Brain O-GlcNAc Cycling in Mouse.

Neurotherapeutics 2021 Jul 26. Epub 2021 Jul 26.

Department of Biomedical Science, Program in Biomedical Science and Engineering, College of Medicine, Inha University, Incheon, Korea.

Rapid eye movement (REM) sleep is implicated learning and memory (L/M) functions and hippocampal long-term potentiation (LTP). Here, we demonstrate that REM sleep deprivation (REMSD)-induced impairment of contextual fear memory in mouse is linked to a reduction in hexosamine biosynthetic pathway (HBP)/O-GlcNAc flux in mouse brain. In mice exposed to REMSD, O-GlcNAcylation, and O-GlcNAc transferase (OGT) were downregulated while O-GlcNAcase was upregulated compared to control mouse brain. Foot shock fear conditioning (FC) induced activation of protein kinase A (PKA) and cAMP response element binding protein (CREB), which were significantly inhibited in brains of the REMSD group. Intriguingly, REMSD-induced defects in L/M functions and FC-induced PKA/CREB activation were restored upon increasing O-GlcNAc cycling with glucosamine (GlcN) or Thiamet G. Furthermore, Thiamet G restored the REMSD-induced decrease in dendritic spine density. Suppression of O-GlcNAcylation by the glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitor, 6-diazo-5-oxo-L-norleucine (DON), or OGT inhibitor, OSMI-1, impaired memory function, and inhibited FC-induced PKA/CREB activation. DON additionally reduced the amplitude of baseline field excitatory postsynaptic potential (fEPSP) and magnitude of long-term potentiation (LTP) in normal mouse hippocampal slices. To our knowledge, this is the first study to provide comprehensive evidence of dynamic O-GlcNAcylation changes during the L/M process in mice and defects in this pathway in the brain of REM sleep-deprived mice. Our collective results highlight HBP/O-GlcNAc cycling as a novel molecular link between sleep and cognitive function.
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http://dx.doi.org/10.1007/s13311-021-01094-7DOI Listing
July 2021

Ultraviolet light-emitting diode-assisted highly sensitive room temperature NO gas sensors based on low-temperature solution-processed ZnO/TiO nanorods decorated with plasmonic Au nanoparticles.

Nanoscale 2021 Jul 14;13(28):12177-12184. Epub 2021 Jul 14.

Department of Advanced Convergence Technology, Korea Polytechnic University, 237 Sangidaehak-ro, Siheung-si, Geyonggi-do 15073, Republic of Korea.

Nanostructured semiconducting metal oxides such as SnO, ZnO, TiO, and CuO have been widely used to fabricate high performance gas sensors. To improve the sensitivity and stability of gas sensors, we developed NO gas sensors composed of ZnO/TiO core-shell nanorods (NRs) decorated with Au nanoparticles (NPs) synthesized via a simple low-temperature aqueous solution process, operated under ultraviolet irradiation to realize room temperature operation. The fabricated gas sensor with a 10 nm-thick TiO shell layer shows 9 times higher gas sensitivity and faster response and recovery times than ZnO NR-based gas sensors. This high performance of the fabricated gas sensor can be ascribed to band bending between the ZnO and TiO core-shell layers and the localized surface plasmon resonance effect of Au NPs with a sufficient Debye length of the TiO shell layer.
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http://dx.doi.org/10.1039/d1nr01001hDOI Listing
July 2021

Overexpression of Hydroxy-2-methyl-2-()-butenyl 4-diphosphate reductase 2 gene () in cv. Xanthi.

3 Biotech 2021 Jul 16;11(7):337. Epub 2021 Jun 16.

Applied Life Chemistry, School of Agricultural Biotechnology, Seoul National University, Seoul, 08826 Korea.

2-C-Methyl-d-erythrol-4-phosphate (MEP) pathway in plant supplies isoprene building blocks for carotenoids and chlorophylls essential in photosynthesis as well as plant hormones such as gibberellin and abscisic acid. To assess the effect of overexpression of the terminal enzyme of the MEP pathway, 1-hydroxy-2-methyl-2-()-butenyl-4-diphosphate reductase (HDR), transgenic overexpressing class 2 HDR from (2) under the control of 35S promoter was constructed. Contents of chlorophylls a and b in transgenic tobacco were enhanced by 19 and 7%, respectively, compared to those of the wild type. The carotenoid level was also 18% higher than that in the control plant. As a result, photosynthetic rate of the transgenic tobacco was increased by up to 51%. Diterepenoid duvatrienediol content of transgenic tobacco was also elevated by at least sixfold. To explore the molecular basis of the enhanced isoprenoid accumulation, transcript levels of the key genes involved in the isoprenoid biosynthesis were measured. Transcript levels of geranylgeranyl diphosphate synthase (), kaurene synthase (), gibberellic acid 20 oxidase (), and phytoene desaturase () genes in the transgenic tobacco leaves were about twofold higher compared to the wild type. Therefore, upregulation of down-stream genes involved in biosynthesis of di- and tetraterpenoids due to overexpression was responsible for elevated production of isoprenoids and enhanced photosynthetic rate.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-02887-5.
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http://dx.doi.org/10.1007/s13205-021-02887-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208371PMC
July 2021

Extracellular Water to Total Body Water Ratio in Septic Shock Patients Receiving Protocol-Driven Resuscitation Bundle Therapy.

J Clin Med 2021 Jun 29;10(13). Epub 2021 Jun 29.

Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

(1) Bio-electrical impedance analysis (BIA) is a rapid, simple, and noninvasive tool for evaluating the metabolic status and for assessing volume status in critically ill patients. Little is known, however, the prognostic value of body composition analysis in septic shock patients. This study assessed the association between parameters by body composition analysis and mortality in patients with septic shock in the emergency department (ED). (2) Data were prospectively collected on adult patients with septic shock who underwent protocol-driven resuscitation bundle therapy between December 2019 and January 2021. The primary outcome was 30-day mortality. (3) The study included 261 patients, the average ratio of extracellular water (ECW) to total body water (TBW) was significantly higher in non-survivors than in survivors (0.414 vs. 0.401, < 0.001). Multivariate analysis showed that ECW/TBW ≥ 0.41 (odds ratio (OR), 4.62; 95% confidence interval (CI), 2.31-9.26, < 0.001), altered mental status (OR, 2.88; 95% CI, 1.28-6.46, = 0.010), and lactate level (OR, 1.24; 95% CI, 1.12-1.37, < 0.001) were significantly associated with 30-day mortality in patients with septic shock. (4) ECW/TBW ≥ 0.41 may be associated with 30-day mortality in patients with septic shock receiving protocol-driven resuscitation bundle therapy in the ED.
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http://dx.doi.org/10.3390/jcm10132917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269068PMC
June 2021

Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloidβ/-Tau accumulation through reduced brain -GlcNAcylation in zebrafish.

J Cereb Blood Flow Metab 2021 Jun 26:271678X211027381. Epub 2021 Jun 26.

Department of Biomedical Science, Program in Biomedical Science and Engineering, College of Medicine, Inha University, Incheon, Korea.

Repetitive hypoxia (RH) exposure affects the initiation and progression of cognitive dysfunction, but little is known about the mechanisms of hypoxic brain damage. In this study, we show that sublethal RH increased anxiety, impaired learning and memory (L/M), and triggered downregulation of brain levels of glucose and several glucose metabolites in zebrafish, and that supplementation of glucose or glucosamine (GlcN) restored RH-induced L/M impairment. Fear conditioning (FC)-induced brain activation of and PKA/CREB signaling was abrogated by RH, and this effect was reversed by GlcN supplementation. RH was associated with decreased brain -GlcNAcylation and an increased -GlcNAcase (OGA) level. RH increased brain inflammation and -Tau and amyloid β accumulation, and these effects were suppressed by GlcN. Our observations collectively suggest that changes in -GlcNAc flux during hypoxic exposure could be an important causal factor for neurodegeneration, and that supplementation of the HBP/-GlcNAc flux may be a potential novel therapeutic or preventive target for addressing hypoxic brain damage.
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http://dx.doi.org/10.1177/0271678X211027381DOI Listing
June 2021

Hypercoagulability in Septic Shock Patients With Thrombocytopenia.

J Intensive Care Med 2021 Jun 9:8850666211024188. Epub 2021 Jun 9.

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

Background: Despite thrombocytopenia, patients with sepsis often experience hypercoagulability. However, limited information is available on the prevalence and effect of hypercoagulability in patients with sepsis-induced thrombocytopenia. Hence, we evaluated the prevalence of hypercoagulability and the association between hypercoagulability and clinical outcomes in septic shock patients with thrombocytopenia.

Methods: Thromboelastography (TEG) was performed prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After excluding 405 patients who did not require resuscitation, refused enrollment, or developed septic shock after ED presentation, 889 patients were included. We defined thrombocytopenia as an admission platelet count lower than 150,000/µl according to SOFA score. We defined hypocoagulability and hypercoagulability as coagulation index (CI)< -3 and >3 on TEG, respectively.

Results: Of the 889 septic shock patients (mean age 65.6 ± 12.7 years, 58.6% male), 473 (53.2%) had thrombocytopenia. Eighty-five (18.0%) patients showed hypercoagulable TEG and73 (15.4%) patients showed hypocoagulable TEG. The hypercoagulable TEG group had a significantly higher fibrinogen level and a lower 28-day mortality rate than the normal and hypocoagulable TEG groups (518 vs. 347 and 315 mg/dL; 7.1% vs. 21.1% and 36.8%, < 0.01, respectively). In multivariate analysis, hypercoagulable TEG was associated with a decreased mortality rate (odds ratio: 0.395; 95% confidence interval, 0.162-0.965).

Conclusions: In septic shock patients with thrombocytopenia, hypercoagulability was not uncommon. TEG can quickly distinguish the hypercoagulability and hypocoagulability states and serve as a valuable tool for evaluating the degree and risk in septic shock patients with thrombocytopenia.
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http://dx.doi.org/10.1177/08850666211024188DOI Listing
June 2021

Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time.

Sci Rep 2021 Jun 4;11(1):11833. Epub 2021 Jun 4.

Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88, Olimpic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.

Coagulopathy is frequent in septic shock and plays a key role in multiple organ dysfunction. The aim of this study is to investigate application values of thromboelastography (TEG) for outcome in septic shock patients with a normal value of prothrombin time (PT) and active partial thromboplastin time (aPTT). Prospective observational study using 1298 consecutive septic shock patients with TEG at admission was conducted at the emergency department (ED) of a tertiary care hospital in South Korea between 2016 and 2019. After excluding overt-disseminated intravascular coagulation (DIC) defined by scoring system, we included patients with a normal value of international normalized ratio ≤ 1.3 and aPTT ≤ 34 s. The primary outcome was 28-day mortality. 893 patients were included and 129 patients with overt DIC were excluded. Of the 764 remaining patients, 414 (54.2%) patients showed normal PT and aPTT (28-day mortality rate, 11.4%). TEG values such as reaction time, kinetic time (K), alpha angle (α), maximum amplitude (MA) and lysis index (LY 30) showed no significant mean difference between the survivor and non-survivor groups. However, hypocoagulable TEG values such as α < 53° (12.0% vs. 23.4%; p = 0.039), and MA < 50 mm (6.3% vs. 21.3%; p = 0.002) were significantly higher in the non-survived group. In multivariate analysis, hypocoagulable state (defined as K > 3 and α < 53 and MA < 50) was independent factors associated with increased risk of death (OR 4.882 [95% CI, 1.698-14.035]; p = 0.003). In conclusion, septic shock patients with normal PT and aPTT can be associated with impaired TEG profile, such as hypocoagulability, associated with increased mortality.
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http://dx.doi.org/10.1038/s41598-021-91221-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178375PMC
June 2021

Modeling Clinical Responses to Targeted Therapies by Patient-Derived Organoids of Advanced Lung Adenocarcinoma.

Clin Cancer Res 2021 Aug 3;27(15):4397-4409. Epub 2021 Jun 3.

Division of Medical Oncology, Yonsei University College of Medicine, Yonsei Cancer Center, Seoul, Korea.

Purpose: Patient-derived organoids (PDO) of lung cancer has been recently introduced, reflecting the genomic landscape of lung cancer. However, clinical relevance of advanced lung adenocarcinoma organoids remains unknown. Here, we examined the ability of PDOs to predict clinical responses to targeted therapies in individual patients and to identify effective anticancer therapies for novel molecular targets.

Experimental Design: Eighty-four organoids were established from patients with advanced lung adenocarcinoma. Formalin-fixed, paraffin-embedded tumor specimens from corresponding patients were analyzed by whole-exome sequencing ( = 12). Organoids were analyzed by whole-exome sequencing ( = 61) and RNA sequencing ( = 55). Responses to mono or combination targeted therapies were examined in organoids and organoid-derived xenografts.

Results: PDOs largely retained somatic alterations including driver mutations of matching patient tumors. PDOs were able to recapitulate progression-free survival and objective responses of patients with non-small cell lung cancer receiving clinically approved tyrosine kinase inhibitors. PDOs recapitulated activity of therapeutic strategies under clinical investigation. YUO-071 harboring an exon 19 deletion and a G464A mutation and the matching patient responded to dabrafenib/trametinib combination therapy. YUO-004 and YUO-050 harboring an L747P mutation was sensitive to afatinib, consistent with the response in the matching patient of YUO-050. Furthermore, we utilized organoids to identify effective therapies for novel molecular targets by demonstrating the efficacy of poziotinib against exon 20 insertions and pralsetinib against fusions.

Conclusions: We demonstrated translational relevance of PDOs in advanced lung adenocarcinoma. PDOs are an important diagnostic tool, which can assist clinical decision making and accelerate development of therapeutic strategies.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-5026DOI Listing
August 2021

Identification of Chemical Compounds from using UPLC-QTOF-MS/MS and their Regulatory Effects on Immune Responses in DSS-Induced Colitis Mice.

Am J Chin Med 2021 6;49(4):941-963. Epub 2021 Apr 6.

Smart Farm Research Center, Gangneung Institute of Natural Products, Korea Institute of Science and Technology (KIST), Gangneung, Gangwon-do 25451, Korea.

Web. ex Stechm. (AG), a popular medicinal herb in Asia, has been used as a common food ingredient in Korea and is traditionally known for its anti-inflammatory properties. Therefore, in this study, we aimed to investigate whether AG relieves IBD, a classic chronic inflammatory disease of the gastrointestinal tract. We identified 35 chemical compounds in AG ethanol extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. In mice with DSS-induced IBD, AG administration attenuated the disease activity index and the serum and colonic levels of inflammatory cytokines and chemokines. AG treatment decreased nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) signaling, a key mediator of inflammation, in the mouse colons. Additionally, AG extract enhanced immune responses in lymphoid tissues such as spleen and Peyer's patches. Thus, AG consumption potently ameliorated IBD symptoms and improved immune signaling in lymphoid tissues.
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http://dx.doi.org/10.1142/S0192415X21500452DOI Listing
April 2021

Determination of Carbohydrate Composition in Mealworm ( L.) Larvae and Characterization of Mealworm Chitin and Chitosan.

Foods 2021 Mar 18;10(3). Epub 2021 Mar 18.

Department of Culinary Arts, Kyungmin University, Uijeongbu 11618, Korea.

Mealworm ( L.) is a classic edible insect with high nutritional value for substituting meats from vertebrates. While interest in mealworms has increased, the determination of carbohydrate constituents of mealworms has been overlooked. Thus, the aim of the present study was to investigate the carbohydrate content and composition of mealworms. In addition, the characteristics of mealworm chitin were determined as these were the major components of mealworm carbohydrate. The crude carbohydrate content of mealworms was 11.5%, but the total soluble sugar content was only 30% of the total carbohydrate content, and fructose was identified as the most abundant free sugar in mealworms. Chitin derivatives were the key components of mealworm carbohydrate with a yield of 4.7%. In the scanning electron microscopy images, a lamellar structure with α-chitin configuration was observed, and mealworm chitosan showed multiple pores on its surface. The overall physical characteristics of mealworm chitin and chitosan were similar to those of the commercial products derived from crustaceans. However, mealworm chitin showed a significantly softer texture than crustacean chitin with superior anti-inflammatory effects. Hence, mealworm chitin and chitosan could be employed as novel resources with unique advantages in industries.
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http://dx.doi.org/10.3390/foods10030640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002850PMC
March 2021

The reasons for ceramic-on-ceramic revisions between the third- and fourth-generation bearings in total hip arthroplasty from multicentric registry data.

Sci Rep 2021 Mar 10;11(1):5539. Epub 2021 Mar 10.

Department of Orthopedic Surgery, Korea University College of Medicine, Anam Hospital, 73 Inchon-ro, Seongbuk-gu, Seoul, 02841, South Korea.

This study aimed to evaluate (1) the overall reasons for first revision in CoC THAs; (2) whether the reasons for revision differ between third-generation and fourth-generation CoC THAs; and (3) the specific factors associated with bearing-related problems as the reason for revision. We retrospectively reviewed 2045 patients (2194 hips) who underwent first revision THA between 2004 and 2013, among which 146 hips with CoC bearings underwent revision. There were 92 hips with third-generation ceramic bearings and 54 hips with fourth-generation ceramic bearings. The major reasons for CoC THA revisions were ceramic fracture and loosening of the cup or stem. When ceramic fracture, squeaking, incorrect ceramic insertion, and unexplained pain were defined as directly related or potentially related to ceramic use, 28.8% (42/146) of CoC revisions were associated with bearing-related problems. Among the third-generation ceramic bearings, revision was performed in 41.3% (38/92) of cases owing to bearing-related problems whereas revisions were performed for only 7.4% (4/54) of cases with fourth-generation ceramic bearings owing to bearing-related problems (p < 0.001). Younger age, lower American Society of Anesthesiologists (ASA) grade, and preoperative diagnosis of osteonecrosis were factors related to CoC THA revisions due to bearing-related problems.
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http://dx.doi.org/10.1038/s41598-021-85193-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946907PMC
March 2021

Cardiac Magnetic Resonance Imaging for Nonischemic Cardiac Disease in Out-of-Hospital Cardiac Arrest Survivors Treated with Targeted Temperature Management: A Multicenter Retrospective Analysis.

J Clin Med 2021 Feb 16;10(4). Epub 2021 Feb 16.

Department of Emergency Medicine, Ulsan University College of Medicine, Asan Medical Center, Seoul 05505, Korea.

(1) Background: Cardiac magnetic resonance (CMR) imaging is an emerging tool for investigating nonischemic cardiomyopathies and cardiac systemic disease. However, data on the cardiac arrest population are limited. This study aimed to evaluate the usefulness of CMR imaging in out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM). (2) Methods: We conducted the retrospective observational study using a multicenter registry of adult non-traumatic comatose OHCA survivors who underwent TTM between January 2010 and December 2019. Of the 949 patients, 389 with OHCA of non-cardiac cause, 145 with significant lesions in the coronary artery, 151 who died during TTM, 81 without further evaluation due to anticipated poor neurological outcome, and 51 whose etiology is underlying disease were excluded. In 36 of the 132 remaining patients, the etiologies included variant angina, long QT syndrome, and complete atrioventricular block in ancillary studies. Fifty-six patients were diagnosed idiopathic ventricular fibrillation without CMR. (3) Results: CMR imaging was performed in the remaining 40 patients with cardiac arrest of unknown cause. The median time from cardiac arrest to CMR imaging was 10.1 days. The CMR finding was normal in 23 patients, non-diagnostic in 12, and abnormal in 5, which suggested non-ischemic cardiomyopathy but did not support the final diagnosis. (4) Conclusions: CMR imaging may not be useful for identifying unknown causes of cardiac arrest in OHCA survivors treated with targeted temperature management without definitive diagnosis even after coronary angiography, echocardiography, and electrophysiology studies. However, further large-scale studies will be needed to confirm these findings.
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http://dx.doi.org/10.3390/jcm10040794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920317PMC
February 2021

Agastache rugosa ethanol extract suppresses bone loss via induction of osteoblast differentiation with alteration of gut microbiota.

Phytomedicine 2021 Apr 14;84:153517. Epub 2021 Feb 14.

Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Republic of Korea. Electronic address:

Purpose: Osteoporosis is a metabolic skeletal disease characterized by bone loss and an increased risk of fractures. This study aimed to investigate the therapeutic effect of Agastache rugosa on postmenopausal osteoporosis and elucidate its mechanisms in modulating the bone status.

Methods And Results: In the osteoblast differentiation process with MC3T3-E1 pre-osteoblasts, ethanol extract of Agastache rugosa (EEAR) and its compounds increased the expression of the proteins and genes of the osteoblast differentiation-related markers such as Runt-related transcription factor 2 (RUNX2) and β-catenin along with the elevation of calcium deposits. An ovariectomized mouse model was utilized to determine the impact of EEAR extract on postmenopausal osteoporosis. Twelve weeks of AR treatment suppressed the loss of bone strength, which was observed through micro-computed tomography. AR elevated osteogenic markers in the bone marrow cells, and collagen type 1 alpha 1 in the distal femoral bone. The results of the 16S rRNA gene sequencing analysis of cecal gut microbiomes demonstrated that AR reversed the ovariectomy-induced changes in the gut microbiomes.

Conclusion: Ethanol extract of Agastache rugosa has a therapeutic effect on postmenopausal osteoporosis via bone morphogenic protein, transforming growth factor β, and Wnt signaling pathway. It also increases the diversity of gut microbiota. Therefore, these data suggest that EEAR could be a potential candidate to treat postmenopausal osteoporosis.
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http://dx.doi.org/10.1016/j.phymed.2021.153517DOI Listing
April 2021

Dual mobility articulation total hip arthroplasty for displaced neck fracture in elderly with neuromuscular disorder.

Injury 2021 Jun 7;52(6):1480-1486. Epub 2021 Jan 7.

Department of Orthopedic Surgery, Korea University College of Medicine, Guro Hospital, Seoul, Republic of Korea. Electronic address:

Purpose: Neuromuscular disease is well known to be at increased risk of complications following hip replacement surgeries. This study is prospectively conducted to investigate clinical performance and survivorship of total hip arthroplasty (THA) using dual mobility articulation in femoral neck fractures of elderly with neuromuscular disease.

Materials And Methods: We prospectively enrolled 162 patients (162 hips) with displaced femoral neck fracture who gave informed consent for dual mobility articulation THA. Of the 162 patients, 35 patients had neuromuscular disease including cerebral palsy, poliomyelitis, hemiplegia, and Parkinson disease (NM group). The other 127 patients had no history of neuromuscular disease (non-NM group). The mean age was 76.5 years (range, 60 - 95) and female ratio was 71.0% (115/162). Clinical outcomes including Harris hip score (HHS), University of California Los Angles activity (UCLA) score were compared between the two groups. Computed tomography and serial radiographs were obtained after surgery. Postoperative complications and reoperation including revision were recorded.

Results: Pain-VAS and all clinical scores of the NM group were comparable to those of the non-NM group. The incidence of dislocation in the NM group did not differ from that in Non-NM group (2/35, 5.7% versus 5/127, 3.9%, p = 0.645). Reoperation was performed in 3 hips (3/35, 8.6%) of the NM group and in 4 hips (4/127, 3.1%) of the non-NM group (p = 0.173). Kaplan-Meier survivorship with an end point of revision for any reason was 97.1% (95% confidence interval [CI], 0.92 to 1.03) in the NM group and 98.4% (95% CI, 0.96 to 1.01) in the non-NM group at 7.3 years after surgery.

Conclusions: In elderly with neuromuscular disease, THA with dual mobility articulation is a reasonable option as a treatment for femoral neck fractures.
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http://dx.doi.org/10.1016/j.injury.2021.01.005DOI Listing
June 2021

Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-κB and NLRP3 inflammasome activation.

Sci Rep 2021 01 12;11(1):543. Epub 2021 Jan 12.

Department of Medical Biotechnology, College of Life Science and Biotechnology, Dongguk University, Seoul, 04620, Republic of Korea.

Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are mediated by the activation of various kinds of signaling pathways in the innate immune system. Particularly, NF-κB and NLRP3 inflammasome signaling are involved in the production and secretion of these cytokines. Each signaling is participated in the two steps necessary for IL-1β, a representative pro-inflammatory cytokine, to be processed into a form secreted by cells. In the priming step stimulated by LPS, pro-IL-1β is synthesized through NF-κB activation. Pro-IL-1β cleavages into mature IL-1β by formed NLRP3 inflammasome in the activation step induced by ATP. The mature form of IL-1β is subsequently secreted out of the cell, causing inflammation. Moreover, IL-6 and TNF-α are known to increase in NLRP3 inflammasome-mediated conditions. Here, we found that fucoxanthin, one of the major components of Phaeodactylum tricornutum, has an inhibitory effect on NF-κB and NLRP3 inflammasome activation induced by the combination of LPS and ATP in bone marrow-derived immune cells as well as astrocytes. Fucoxanthin, which is abundant in the EtOH fraction of Phaeodactylum tricornutum extracts, has shown to have less cell toxicity and found to decrease the production of major pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Fucoxanthin has also shown to suppress the expression of cleaved caspase-1 and the oligomerization of ASC, which are the main components of the NLRP3 inflammasome. Furthermore, phosphorylated IκBα and pro-IL-1β expression decreased in the presence of fucoxanthin, suggesting that fucoxanthin can negatively regulate the priming step of inflammasome signaling. Thus, our results provide reliable evidence that fucoxanthin may serve as a key candidate in the development of potential therapeutic agents for inflammatory diseases as well as neurodegenerative diseases caused by NF-κB and NLRP3 inflammasome activation.
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http://dx.doi.org/10.1038/s41598-020-80748-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803995PMC
January 2021

Evogliptin Suppresses Calcific Aortic Valve Disease by Attenuating Inflammation, Fibrosis, and Calcification.

Cells 2021 01 1;10(1). Epub 2021 Jan 1.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Calcific aortic valve disease (CAVD) accompanies inflammatory cell infiltration, fibrosis, and ultimately calcification of the valve leaflets. We previously demonstrated that dipeptidyl peptidase-4 (DPP-4) is responsible for the progression of aortic valvular calcification in CAVD animal models. As evogliptin, one of the DPP-4 inhibitors displays high specific accumulation in cardiac tissue, we here evaluated its therapeutic potency for attenuating valvular calcification in CAVD animal models. Evogliptin administration markedly reduced calcific deposition accompanied by a reduction in proinflammatory cytokine expression in endothelial nitric oxide synthase-deficient mice in vivo, and significantly ameliorated the mineralization of the primary human valvular interstitial cells (VICs), with a reduction in the mRNA expression of bone-associated and fibrosis-related genes in vitro. In addition, evogliptin ameliorated the rate of change in the transaortic peak velocity and mean pressure gradients in our rabbit model as assessed by echocardiography. Importantly, evogliptin administration in a rabbit model was found to suppress the effects of a high-cholesterol diet and of vitamin D2-driven fibrosis in association with a reduction in macrophage infiltration and calcific deposition in aortic valves. These results have indicated that evogliptin prohibits inflammatory cytokine expression, fibrosis, and calcification in a CAVD animal model, suggesting its potential as a selective therapeutic agent for the inhibition of valvular calcification during CAVD progression.
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http://dx.doi.org/10.3390/cells10010057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824080PMC
January 2021

Role of Thromboelastography as an Early Predictor of Disseminated Intravascular Coagulation in Patients with Septic Shock.

J Clin Med 2020 Nov 29;9(12). Epub 2020 Nov 29.

Department of Emergency Medicine, Ulsan University College of Medicine, Asan Medical Center, Seoul 05505, Korea.

(1) Background: The currently proposed criteria for diagnosing overt disseminated intravascular coagulation (DIC) are not suitable for early detection of DIC. Thromboelastography (TEG) rapidly provides a comprehensive assessment of the entire coagulation process and is helpful as a guide for correcting consumptive coagulopathy in sepsis-induced DIC. This study aimed to investigate the role of TEG in the prediction of DIC in patients with septic shock. (2) Methods: TEG was conducted prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After exclusion of 405 patients with "do not attempt resuscitation" orders, those refusing enrollment, and those developing septic shock after ED presentation, 889 patients were included. DIC was defined as an International Society on Thrombosis and Hemostasis score ≥ 5 points within 24 h. (3) Results: Of the 889 patients with septic shock (mean age 65.6 ± 12.7 years, 58.6% male), 158 (17.8%) developed DIC. TEG values, except lysis after 30 min, were significantly different between the DIC and non-DIC groups. Among the TEG values, the maximal amplitude (MA) had the highest discriminating power for DIC, with an area under the curve of 0.814. An MA < 60 indicated DIC with 79% sensitivity, 73% specificity, and 94% negative predictive value. Based on multivariable analysis, MA < 60 was an independent predictor of DIC (odds ratio 5.616 (95% confidence interval: 3.213-9.818)). (4) Conclusions: In patients with septic shock, the MA value in TEG could be a valuable tool for early prediction of DIC.
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http://dx.doi.org/10.3390/jcm9123883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760761PMC
November 2020

Soybean Viromes in the Republic of Korea Revealed by RT-PCR and Next-Generation Sequencing.

Microorganisms 2020 Nov 12;8(11). Epub 2020 Nov 12.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.

Soybean ( L.) is one of the most important crop plants in the Republic of Korea. Here, we conducted a soybean virome study. We harvested a total of 172 soybean leaf samples showing disease symptoms from major soybean-growing regions in the Republic of Korea. Individual samples were examined for virus infection by RT-PCR. Moreover, we generated eight libraries representing eight provinces by pooling samples and four libraries from single samples. RNA-seq followed by bioinformatics analyses revealed 10 different RNA viruses infecting soybean. The proportion of viral reads in each transcriptome ranged from 0.2 to 31.7%. Coinfection of different viruses in soybean plants was very common. There was a single dominant virus in each province, and this geographical difference might be related to the soybean seeds that transmit viruses. In this study, 32 viral genome sequences were assembled and successfully used to analyze the phylogenetic relationships and quasispecies nature of the identified RNA viruses. Moreover, RT-PCR with newly developed primers confirmed infection of the identified viruses in each library. Taken together, our soybean virome study provides a comprehensive overview of viruses infecting soybean in eight geographical regions in the Republic of Korea and four single soybean plants in detail.
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http://dx.doi.org/10.3390/microorganisms8111777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698195PMC
November 2020

The In Vitro and In Planta Interspecies Interactions Among Rice-Pathogenic Species.

Plant Dis 2021 Jan 16;105(1):134-143. Epub 2020 Nov 16.

Department of Microbiology, Pusan National University, Busan 46241, Korea.

, , and are responsible for serious diseases in rice crops and co-occurrence among them has been reported. In this study, in vitro assays revealed antagonistic activity among these organisms, with demonstrating strong inhibition of and . Strains of and that express green fluorescent protein were constructed and used for cocultivation assays with , which confirmed the strong inhibitory activity of . Cell-free supernatants from each species were tested against cultures of counterpart species to evaluate the potential to inhibit bacterial growth. To investigate the inhibitory activity of on and in rice, rice plant assays were performed and quantitative PCR (qPCR) assays were developed for in planta bacterial quantification. The results indicated that coinoculation with leads to significantly reduced disease severity and colonization of rice tissues compared with single inoculation with or . This study demonstrates the interactions among three rice-pathogenic species and strong antagonistic activity of in vitro and in planta. The qPCR assays developed here could be applied for accurate quantification of these organisms from in planta samples in future studies.
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http://dx.doi.org/10.1094/PDIS-06-20-1252-REDOI Listing
January 2021

Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid and Sensitive Detection of Barley Yellow Dwarf Virus in Oat.

Plant Pathol J 2020 Oct;36(5):497-502

Department of Applied Biology, Institute of Environmentally Friendly Agriculture, Chonnam National University, Gwangju 685, Korea.

Barley yellow dwarf virus (BYDV) is an economically important plant pathogen that causes stunted growth, delayed heading, leaf yellowing, and purple leaf tip, thereby reducing the yields of cereal crops worldwide. In the present study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed for the detection of BYDV in oat leaf samples. The RT-RPA assay involved incubation at an isothermal temperature (42°C) and could be performed rapidly in 5 min. In addition, no cross-reactivity was observed to occur with other cereal-infecting viruses, and the method was 100 times more sensitive than conventional reverse transcription polymerase chain reaction. Furthermore, the assay was validated for the detection of BYDV in both field-collected oat leaves and viruliferous aphids. Thus, the RT-RPA assay developed in the present study represents a simple, rapid, sensitive, and reliable method for detecting BYDV in oats.
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http://dx.doi.org/10.5423/PPJ.NT.08.2020.0148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542026PMC
October 2020

Monolithic Dual Mobility Cup Total Hip Arthroplasty Has High Complication Rates With Surgical Fixation in Elderly With Femur Neck Fracture.

J Arthroplasty 2020 12 6;35(12):3621-3626. Epub 2020 Jul 6.

Department of Orthopedic Surgery, Korea University College of Medicine, Guro Hospital, Seoul, Republic of Korea.

Background: This study is prospectively conducted to evaluate surgical complications of monolithic dual mobility cup total hip arthroplasty (THA) in elderly patients with fractured neck of the femur.

Methods: Ninety-seven patients (97 hips) with displaced femoral neck fracture who gave informed consent for participation were prospectively enrolled. Their mean age was 76.6 years (range, 60-95 years), and the mean bone mineral density T-score of neck of the femur was -2.8 (range, -1.2 to -5.5). All patients underwent THA with monolithic dual mobility cup, and computed tomography scans were obtained to evaluate radiographic parameters including anteversion, inclination, and loosening of acetabular cups, and periprosthetic acetabular fractures.

Results: With regard to cup orientation, mean inclination angle was 40.2° (range, 23.5°-63°) and mean anteversion was 32.6° (range, 7°-66.2°). The proportion of surgical outliers was 10.3% (10/97) in inclination and 35.1% (34/97) in anteversion. Early cup loosening within 2 weeks was detected in 2 hips. Periprosthetic acetabular fractures were identified in 6 hips (6/97, 6.2%). Of the 6 fractures, 5 nondisplaced fractures were healed with conservative management, but 1 fracture with displacement eventually led to cup loosening and the patient underwent revision surgery. Reoperation rate of the monolithic dual mobility cup was 4.1% (4/97).

Conclusion: The use of the monolithic dual mobility was associated with improper cup fixation and periprosthetic acetabular fractures in the elderly with poor bone stock, although the dual mobility cup lowered the risk of early dislocation after THA.
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http://dx.doi.org/10.1016/j.arth.2020.06.091DOI Listing
December 2020

Assessment of the conventional radial artery with optical coherent tomography after the snuffbox approach.

Cardiol J 2020 Jul 25. Epub 2020 Jul 25.

Division of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea.

Background: This study aimed to evaluate acute injuries of the radial artery (RA) using optical coherence tomography (OCT) in patients who underwent coronary intervention via the snuffbox approach.

Methods: Forty-six patients, who underwent coronary intervention and assessment of the conventional RA using OCT via the snuffbox approach, were enrolled from two university hospitals between August 2018 and August 2019.

Results: The mean age of the patients was 65.1 years. In this study population, 6-French (Fr) sheaths were used. The mean diameter of the conventional RA was 2.89 ± 0.33 mm, and the mean lumen area of the conventional RA was 6.68 ± 1.56 mm². Acute injuries of the conventional RA, after the snuffbox approach, were observed in 5 (10.9%) patients. Intimal tear was observed in the RA in 1 (2.2%) case. Intraluminal thrombi, without vessel injuries, were detected in the RA in 4 (8.7%) cases. However, medial dissection was not observed in the OCT analysis.

Conclusions: This retrospective OCT-based study showed that the diameter of the conventional RA was 2.89 mm and acute vessel injury of the conventional RA was rare in patients who underwent coronary intervention via the snuffbox approach.
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http://dx.doi.org/10.5603/CJ.a2020.0097DOI Listing
July 2020

Glucosamine regulates hepatic lipid accumulation by sensing glucose levels or feeding states of normal and excess.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 10 11;1865(10):158764. Epub 2020 Jul 11.

Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Republic of Korea. Electronic address:

Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver of normal fed zebrafish larvae. High glucose (HG, 25 mM)-induced lipid accumulation was suppressed by l-glutamine-d-fructose 6-phosphate amidotransferase inhibitors. ER stress inhibitors did not suppress HG or GlcN-mediated lipid accumulation. HG and GlcN stimulated protein expression, DNA binding and O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP). Furthermore, both HG and GlcN increased nuclear sterol regulatory element-binding protein-1 (SREBP-1) levels in HepG2 cells. In contrast to its stimulatory effect under NG, GlcN suppressed lipid accumulation in HepG2 cells under HG conditions. Similarly, GlcN suppressed lipid accumulation in livers of overfed zebrafish. In addition, GlcN activity on DNA binding and O-GlcNAcylation of ChREBP was stimulatory under NG and inhibitory under HG conditions. Moreover, GlcN enhanced ChREBP, SREBP-1c, ACC, FAS, L-PK and SCD-1 mRNA expression under NG but inhibited HG-induced upregulation in HepG2 cells. The O-GlcNAc transferase inhibitor, alloxan, reduced lipid accumulation by HG or GlcN while the O-GlcNAcase inhibitor, PUGNAc, enhanced lipid accumulation in HepG2 cells and liver of zebrafish larvae. GlcN-induced lipid accumulation was inhibited by the AMPK activator, AICAR. Phosphorylation of AMPK (p-AMPK) was suppressed by GlcN under NG while increased by GlcN under HG. PUGNAc downregulated p-AMPK while alloxan restored GlcN- or HG-induced p-AMPK inhibition. Our results collectively suggest that GlcN regulates lipogenesis by sensing the glucose or energy states of normal and excess fuel through AMPK modulation.
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http://dx.doi.org/10.1016/j.bbalip.2020.158764DOI Listing
October 2020

Lemon Balm and Its Constituent, Rosmarinic Acid, Alleviate Liver Damage in an Animal Model of Nonalcoholic Steatohepatitis.

Nutrients 2020 Apr 22;12(4). Epub 2020 Apr 22.

Smart Farm Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Korea.

Nonalcoholic fatty liver disease (NAFLD) ranges in severity from hepatic steatosis to cirrhosis. Lemon balm and its major constituent, rosmarinic acid (RA), effectively improve the liver injury and obesity; however, their therapeutic effects on nonalcoholic steatohepatitis (NASH) are unknown. In this study, we investigated the effects of RA and a lemon balm extract (LBE) on NAFLD and liver fibrosis and elucidated their mechanisms. Palmitic acid (PA)-exposed HepG2 cells and db/db mice fed a methionine- and choline-deficient (MCD) diet were utilized to exhibit symptoms of human NASH. LBE and RA treatments alleviated the oxidative stress by increasing antioxidant enzymes and modulated lipid metabolism-related gene expression by the activation of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis and inflammation in vitro and in vivo. Together, LBE and RA could improve liver damage by non-alcoholic lipid accumulation and may be promising medications to treat NASH.
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http://dx.doi.org/10.3390/nu12041166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230626PMC
April 2020

A Comparison of U-blade Gamma3 and Gamma3 Nails Used for the Treatment of Intertrochanteric Fractures.

Hip Pelvis 2020 Mar 26;32(1):50-57. Epub 2020 Feb 26.

Department of Orthopedic Surgery, Seoul Medical Center, Seoul, Korea.

Purpose: To compare outcomes (i.e., clinical and radiological findings, postoperative complication) in the fixation of intertrochanteric fractures with U-blade Gamma3 and Gamma3 nails.

Materials And Methods: A review of 162 patients (both male and female) treated for intertrochanteric fractures between December 2012 and December 2018 was conducted. All patients were older than 65 years of age and treated with U-blade Gamma3 (n=90) or Gamma3 (n=72) nails. Evaluations included: (i) screw-head position, (ii) fracture-reduction status, (iii) time to union, (iv) cases of cut-out, (v) tip-apex distance, and (vi) lag screw sliding distance. Differences in pre- and postoperative ambulatory ability was also investigated.

Results: There were no significant differences in baseline demographics between the two groups. While the lag-screw sliding distance was significantly shorter in U-blade Gamma3 nail group (4.7 mm vs. 3.6 mm; =0.025), the mean time to union was similar between the groups (=0.053). Three and six cases of cut-out were noted in the U-blade Gamma3 and Gamma3 nail groups, respectively (=0.18), however no other postoperative complications were noted in either group. Lastly, there was no difference between the change from pre- to postoperative activity level between the groups (=0.753).

Conclusion: Of all the clinical and radiological outcomes assessed, the only significant improvement between those treated with U-Blade Gamma and Gamma3 nails was a shorter lag-screw sliding distance. These findings should benefit clinicians when deciding between the use of U-Blade Gamma or Gamma3 nails.
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http://dx.doi.org/10.5371/hp.2020.32.1.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054077PMC
March 2020

Lack of prognostic significance for major adverse cardiac events of soluble suppression of tumorigenicity 2 levels in patients with ST-segment elevation myocardial infarction.

Cardiol J 2021 27;28(2):244-254. Epub 2020 Feb 27.

Chungbuk Regional Cardiovascular Center, Chungbuk National University Hospital, Cheongju, Korea, Republic Of.

Background: Elevation of soluble suppression of tumorigenicity 2 (sST2) is associated with cardiac fibrosis and hypertrophy. Under investigation herein, was whether sST2 level is associated with major adverse cardiac events (MACE) and left ventricular (LV) remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods: In total, this study included 184 patients who underwent successful primary PCI. A subsequent guideline-based medical follow-up was included (61.4 ± 11.8 years old, 85% male, 21% with Killip class ≥ I). sST2 concentration correlations with echocardiographic, angiographic, laboratory parameters, and clinical outcomes in STEMI patients were evaluated.

Results: The median sST2 level was 60.3 ng/mL; 6 (3.2%) deaths occurred within 1 year. The sST2 level correlated with LV ejection fraction (LVEF) changes from baseline to 6 months (r= -0.273; p = 0.006) after adjustment for echocardiographic parameters including wall motions score index (WMSI). Recovery of LVEF at 6 months was highest in the tertile 1 group (Δ6 months - baseline LVEF; tertile 1, p = 0.001; tertile 2, p = 0.319; tertile 3, p = 0.205). The decrease in WMSI at 6 months was greater in the tertiles 1 and 2 groups than in the tertile 3 group (Δ6 months - baseline WMSI; tertile 1, p = 0.001; tertile 2, p = 0.013; tertile 3, p = 0.055). There was no association between sST2 levels and short-term (log rank p = 0.598) and long-term (p = 0.596) MACE.

Conclusions: sST2 concentration have predictive value for LV remodeling on echocardiography in patients with STEMI who underwent primary PCI. However, sST2 concentration was not associated with short-term and long-term MACE.
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http://dx.doi.org/10.5603/CJ.a2020.0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078943PMC
September 2021

Sweet potato viromes in eight different geographical regions in Korea and two different cultivars.

Sci Rep 2020 02 13;10(1):2588. Epub 2020 Feb 13.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

The sweet potato in the family Convolvulaceae is a dicotyledonous perennial plant. Here, we conducted a comprehensive sweet potato virome study using 10 different libraries from eight regions in Korea and two different sweet potato cultivars by RNA-Sequencing. Comprehensive bioinformatics analyses revealed 10 different virus species infecting sweet potato. Moreover, we identified two novel viruses infecting sweet potato referred to as Sweet potato virus E (SPVE) in the genus Potyvirus and Sweet potato virus F (SPVF) in the genus Carlavirus. Of the identified viruses, Sweet potato feathery mottle virus (SPFMV) was the dominant virus followed by Sweet potato virus C (SPVC) and SPVE in Korea. We obtained a total of 30 viral genomes for eight viruses. Our phylogenetic analyses showed many potyvirus isolates are highly correlated with geographical regions. However, two isolates of SPFMV and a single isolate of Sweet potato virus G (SPVG) were genetically distant from other known isolates. The mutation rate was the highest in SPFMV followed by SPVC and SPVG. Two different sweet potato cultivars, Beni Haruka and Hogammi, were infected by seven and five viruses, respectively. Taken together, we provide a complete list of viruses infecting sweet potato in Korea and diagnostic methods.
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http://dx.doi.org/10.1038/s41598-020-59518-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018812PMC
February 2020

Estimation of spatially continuous daytime particulate matter concentrations under all sky conditions through the synergistic use of satellite-based AOD and numerical models.

Sci Total Environ 2020 Apr 8;713:136516. Epub 2020 Jan 8.

Department of Environmental Resources Engineering, State University of New York, College of Environmental Science and Forestry, Syracuse, NY 13210, USA.

Satellite-derived aerosol optical depth (AOD) products are one of main predictors to estimate ground-level particulate matter (PM and PM) concentrations. Since AOD products, however, are only provided under high-quality conditions, missing values usually exist in areas such as clouds, cloud shadows, and bright surfaces. In this study, spatially continuous AOD and subsequent PM and PM concentrations were estimated over East Asia using satellite- and model-based data and auxiliary data in a Random Forest (RF) approach. Data collected from the Geostationary Ocean Color Imager (GOCI; 8 times per day) in 2016 were used to develop AOD and PM models. Three schemes (i.e. G1, A1, and A2) were proposed for AOD modeling according to target AOD data (GOCI AOD and AERONET AOD) and the existence of satellite-derived AOD. The A2 scheme showed the best performance (validation R of 0.74 and prediction R of 0.73 when GOCI AOD did not exist) and the resultant AOD was used to estimate spatially continuous PM concentrations. The PM models with location information produced successful estimation results with R of 0.88 and 0.90, and rRMSE of 26.9 and 27.2% for PM and PM, respectively. The spatial distribution maps of PM well captured the seasonal and spatial characteristics of PM reported in the literature, which implies the proposed approaches can be adopted for an operational estimation of spatially continuous AOD and PMs under all sky conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.136516DOI Listing
April 2020

Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling.

Cells 2020 01 6;9(1). Epub 2020 Jan 6.

Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

The interleukin-22 (IL-22) signaling pathway is well known to be involved in the progression of various cancer types but its role in bone metastatic breast cancer remains unclear. We demonstrate using human GEO profiling that bone metastatic breast cancer displays elevated interleukin-22 receptor 1 (IL-22R1) and sphingosine-1-phosphate receptor 1 (S1PR1) expression. Importantly, IL-22 stimuli promoted the expression of IL-22R1 and S1PR1 in aggressive MDA-MB-231 breast cancer cells. IL-22 treatment also increased sphingosine-1-phosphate production in mesenchymal stem cells (MSCs) and induced the sphingosine-1-phosphate (S1P)-mediated chemotactic migration of MDA-MB-231 cells. This effect was inhibited by an S1P antagonist. In addition to the S1PR1 axis, IL-22 stimulated the expression of matrix metalloproteinase-9 (MMP-9), thereby promoting breast cancer cell invasion. Moreover, IL-22 induced IL22R1 and S1PR1 expression in macrophages, myeloid cell, and MCP1 expression in MSCs to facilitate macrophage infiltration. Immunohistochemistry indicated that IL-22R1 and S1PR1 are overexpressed in invasive malignant breast cancers and that this correlates with the MMP-9 levels. Collectively, our present results indicate a potential role of IL-22 in driving the metastasis of breast cancers into the bone microenvironment through the IL22R1-S1PR1 axis.
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http://dx.doi.org/10.3390/cells9010131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017200PMC
January 2020

Sleep deprivation impairs learning and memory by decreasing protein O-GlcNAcylation in the brain of adult zebrafish.

FASEB J 2020 01 27;34(1):853-864. Epub 2019 Nov 27.

Department of Physiology and Biophysics, College of Medicine, Inha University, Incheon, Korea.

Sleep is an evolutionarily conserved physiological process implicated in the consolidation of learning and memory (L/M). Here, we report that sleep deprivation (SD)-induced cognitive deficits in zebrafish are mediated through reduction in O-GlcNAcylation of brain. Microarray-based gene expression profiling of zebrafish brain demonstrated significant changes in genes involved in metabolism by SD or fear conditioning (FC), compared to the control group. In particular, it was observed that a marked decrease in the number of genes involved in carboxylic acid and organic acid metabolic processes in the brains of SD group compared to control group. SD downregulated O-GlcNAc transferase (OGT) and O-GlcNAcylation, while the expression of O-GlcNAcase was upregulated. FC activated protein kinase A (PKA) and phosphorylated cAMP response element binding protein (p-CREB), an effect that was greatly inhibited by SD. Moreover, FC upregulated expressions of OGT and increased O-GlcNAcylation in the brains of normal but not SD zebrafish. Intriguingly, upregulation of O-GlcNAcylation by glucosamine restored defects in L/M functions and PKA/p-CREB activity in SD group. Our findings highlight the O-GlcNAcylation changes in the brain during the L/M process and further provide a foundation for future studies seeking the molecular and biochemical mechanisms by which HBP of glucose metabolism affects cognitive function.
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http://dx.doi.org/10.1096/fj.201901399RRDOI Listing
January 2020
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