Publications by authors named "Dong-Young Kim"

291 Publications

The CAGE-MiR-181b-5p-S1PR1 Axis Regulates Anticancer Drug Resistance and Autophagy in Gastric Cancer Cells.

Front Cell Dev Biol 2021 25;9:666387. Epub 2021 May 25.

Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, South Korea.

Cancer-associated gene (CAGE), a cancer/testis antigen, has been known to promote anticancer drug resistance. Since the underlying mechanisms of CAGE-promoted anticancer drug resistance are poorly understood, we established Anticancer drug-resistant gastric cancer cells (AGS ) to better elucidate possible mechanisms. AGS showed an increased expression level of CAGE and autophagic flux compared with anticancer drug-sensitive parental gastric cancer cells (AGS cells). AGS cells showed higher invasion potential, growth rate, tumor spheroid formation, and angiogenic potential than AGS cells. CAGE exerted effects on the response to anticancer drugs and autophagic flux. CAGE was shown to bind to Beclin1, a mediator of autophagy. Overexpression of CAGE increased autophagic flux and invasion potential but inhibited the cleavage of PARP in response to anticancer drugs in CAGE CRISPR-Cas9 cell lines. TargetScan analysis was utilized to predict the binding of miR-302b-5p to the promoter sequences of CAGE, and the results show that miR-302b-5p directly regulated CAGE expression as illustrated by luciferase activity. MiR-302b-5p regulated autophagic flux and the response to anticancer drugs. CAGE was shown to bind the promoter sequences of miR-302b-5p. The culture medium of AGS cells increased CAGE expression and autophagic flux in AGS cells. ImmunoEM showed CAGE was present in the exosomes of AGS cells; exosomes of AGS cells and human recombinant CAGE protein increased CAGE expression, autophagic flux, and resistance to anticancer drugs in AGS cells. MicroRNA array revealed miR-181b-5p as a potential negative regulator of CAGE. MiR-181b-5p inhibitor increased the expression of CAGE and autophagic flux in addition to preventing anticancer drugs from cleaving poly(ADP-ribose) polymerase (PARP) in AGS cells. TargetScan analysis predicted sphingosine 1-phosphate receptor 1 (SIPR1) as a potential target for miR-181b-5p. CAGE showed binding to the promoter sequences of S1PR1. The downregulation or inhibition of S1PR1 led to decreased autophagic flux but enhanced the sensitivity to anticancer drugs in AGS cells. This study presents a novel role of the CAGE-miR-181b-5p-S1PR1 axis in anticancer drug resistance and autophagy.
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http://dx.doi.org/10.3389/fcell.2021.666387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185229PMC
May 2021

A case of nontuberculous mycobacteria-associated thyroiditis mimicking subacute thyroiditis.

Acta Radiol Open 2021 May 31;10(5):20584601211021504. Epub 2021 May 31.

Department of Otolaryngology-Head & Neck Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.

We describe a case of nontuberculous mycobacteria infection in the thyroid gland in a 54-year-old woman who had painful thyroid enlargement. Ultrasonography showed ill-defined hypoechoic lesions without increased vascularity in both upper lobes of the thyroid gland. Fine needle aspiration biopsy was performed, and pathology showed granulomatous inflammation with necrotic debris that the pathologist suspected was subacute granulomatous thyroiditis or tuberculosis of the thyroid gland. Nontuberculous mycobacteria infection was confirmed after right hemithyroidectomy. Antimycobacterial therapy was initiated as the treatment of choice. Nontuberculous mycobacteria in the thyroid gland appear to be rare. In clinical practice, however, it should be considered as a differential diagnosis of a painful thyroid mass. For accurate diagnosis, clinical and radiological features plus histological examination are required.
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http://dx.doi.org/10.1177/20584601211021504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172948PMC
May 2021

CO doping of organic interlayers for perovskite solar cells.

Nature 2021 Jun 2;594(7861):51-56. Epub 2021 Jun 2.

Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, New York, NY, USA.

In perovskite solar cells, doped organic semiconductors are often used as charge-extraction interlayers situated between the photoactive layer and the electrodes. The π-conjugated small molecule 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer, and its electrical properties considerably affect the charge collection efficiencies of the solar cell. To enhance the electrical conductivity of spiro-OMeTAD, lithium bis(trifluoromethane)sulfonimide (LiTFSI) is typically used in a doping process, which is conventionally initiated by exposing spiro-OMeTAD:LiTFSI blend films to air and light for several hours. This process, in which oxygen acts as the p-type dopant, is time-intensive and largely depends on ambient conditions, and thus hinders the commercialization of perovskite solar cells. Here we report a fast and reproducible doping method that involves bubbling a spiro-OMeTAD:LiTFSI solution with CO under ultraviolet light. CO obtains electrons from photoexcited spiro-OMeTAD, rapidly promoting its p-type doping and resulting in the precipitation of carbonates. The CO-treated interlayer exhibits approximately 100 times higher conductivity than a pristine film while realizing stable, high-efficiency perovskite solar cells without any post-treatments. We also show that this method can be used to dope π-conjugated polymers.
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http://dx.doi.org/10.1038/s41586-021-03518-yDOI Listing
June 2021

Electrodiagnostic, Sonographic, and Clinical Features of Carpal Tunnel Syndrome with Bifid Median Nerve.

J Pain Res 2021 18;14:1259-1269. Epub 2021 May 18.

Department of Neurosurgery, Spine and Joint Center, Pohang Stroke and Spine Hospital, Pohang, Republic of Korea.

Purpose: A bifid median nerve (BMN) is not a rare variant. This study aimed to investigate the features of carpal tunnel syndrome (CTS) accompanied by BMN.

Patients And Methods: In this retrospective study, we defined a BMN group as CTS with BMN and a non-bifid median nerve (NMN) group as CTS without BMN. All hands were assigned to four severity grades according to the findings of electrodiagnosis (EDx): very mild, mild, moderate, and severe. The cross-sectional area (CSA) of the median nerve, palmar bowing of the flexor retinaculum, and persistent median artery (PMA) were assessed by ultrasonography. Numerical pain rating scale (NRS) and symptom duration were assessed as clinical variables.

Results: Sixty-four hands (57 patients) and 442 hands (341 patients) were enrolled in the BMN and the NMN groups, respectively. BMN was prevalent in 12.6% of all CTS hands. The distribution of EDx severity grade was milder in the BMN group than in the NMN group (<0.001). The CSA of the BMN group was 16.2±4.1 mm, slightly larger than 15.1±4.2 mm in the NMN group (=0.056). The BMN group showed higher NRS than the NMN group (5.5±1.5 and 4.4±1.7, respectively; <0.001). In the subgroup analysis, NRS was significantly higher in the BMN group than in the NMN group at all EDx severity grades. In the BMN group, the PMA group showed greater EDx severity (=0.037) and higher NRS (6.0 and 5.0, respectively; =0.012) than the non-PMA group. The radial side branch's CSA was larger than that of the ulnar side branch (10.0 mm and 6.0 mm, respectively; 0.001).

Conclusion: CTS with BMN presented more severe symptoms and relatively milder EDx severity. When assessing the severity of CTS with BMN, the clinical symptoms should primarily be considered, as well as we should complementarily evaluate the EDx and ultrasonography.
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http://dx.doi.org/10.2147/JPR.S303142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140939PMC
May 2021

Identification of recombinant Fabs for structural and functional characterization of HIV-host factor complexes.

PLoS One 2021 13;16(5):e0250318. Epub 2021 May 13.

Department of Pharmaceutical Chemistry, University of California, San Francisco, California, United States of America.

Viral infection and pathogenesis is mediated by host protein-viral protein complexes that are important targets for therapeutic intervention as they are potentially less prone to development of drug resistance. We have identified human, recombinant antibodies (Fabs) from a phage display library that bind to three HIV-host complexes. We used these Fabs to 1) stabilize the complexes for structural studies; and 2) facilitate characterization of the function of these complexes. Specifically, we generated recombinant Fabs to Vif-CBF-β-ELOB-ELOC (VCBC); ESCRT-I complex and AP2-complex. For each complex we measured binding affinities with KD values of Fabs ranging from 12-419 nM and performed negative stain electron microscopy (nsEM) to obtain low-resolution structures of the HIV-Fab complexes. Select Fabs were converted to scFvs to allow them to fold intracellularly and perturb HIV-host protein complex assembly without affecting other pathways. To identify these recombinant Fabs, we developed a rapid screening pipeline that uses quantitative ELISAs and nsEM to establish whether the Fabs have overlapping or independent epitopes. This pipeline approach is generally applicable to other particularly challenging antigens that are refractory to immunization strategies for antibody generation including multi-protein complexes providing specific, reproducible, and renewable antibody reagents for research and clinical applications. The curated antibodies described here are available to the scientific community for further structural and functional studies on these critical HIV host-factor proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250318PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118348PMC
May 2021

DEP-induced ZEB2 promotes nasal polyp formation via epithelial-to-mesenchymal transition.

J Allergy Clin Immunol 2021 May 4. Epub 2021 May 4.

Obstructive Upper airway Research Laboratory, the Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address:

Background: Diesel exhaust particles (DEPs) are associated with the prevalence and exacerbation of allergic respiratory diseases, including allergic rhinitis and allergic asthma. However, DEP-induced mechanistic pathways promoting upper airway disease and their clinical implications remain unclear.

Objective: We sought to investigate the mechanisms by which DEP exposure contributes to nasal polyposis using human-derived epithelial cells and a murine nasal polyp (NP) model.

Methods: Gene set enrichment and weighted gene coexpression network analyses were performed. Cytotoxicity, epithelial-to-mesenchymal transition (EMT) markers, and nasal polyposis were assessed. Effects of DEP exposure on EMT were determined using epithelial cells from normal people or patients with chronic rhinosinusitis with or without NPs. BALB/c mice were exposed to DEP through either a nose-only exposure system or nasal instillation, with or without house dust mite, followed by zinc finger E-box-binding homeobox (ZEB)2 small hairpin RNA delivery.

Results: Bioinformatics analyses revealed that DEP exposure triggered EMT features in airway epithelial cells. Similarly, DEP-exposed human nasal epithelial cells exhibited EMT characteristics, which were dependent on ZEB2 expression. Human nasal epithelial cells derived from patients with chronic rhinosinusitis presented more prominent EMT features after DEP treatment, when compared with those from control subjects and patients with NPs. Coexposure to DEP and house dust mite synergistically increased the number of NPs, epithelial disruptions, and ZEB2 expression. Most importantly, ZEB2 inhibition prevented DEP-induced EMT, thereby alleviating NP formation in mice.

Conclusions: Our data show that DEP facilitated NP formation, possibly via the promotion of ZEB2-induced EMT. ZEB2 may be a therapeutic target for DEP-induced epithelial damage and related airway diseases, including NPs.
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http://dx.doi.org/10.1016/j.jaci.2021.04.024DOI Listing
May 2021

Adenotonsillectomy may increase the risk of alopecia areata in childhood: A nationwide population-based cohort study.

J Am Acad Dermatol 2021 Apr 18. Epub 2021 Apr 18.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea; Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.04.025DOI Listing
April 2021

Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists.

J Korean Med Sci 2021 Apr 19;36(15):e97. Epub 2021 Apr 19.

Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

Background: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy.

Methods: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA).

Results: The median age and median follow-up period were 31 (16-73) years and 139.1 (12.2-319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality.

Conclusion: TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.
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http://dx.doi.org/10.3346/jkms.2021.36.e97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055511PMC
April 2021

Microbiome profiling of uncinate tissue and nasal polyps in patients with chronic rhinosinusitis using swab and tissue biopsy.

PLoS One 2021 8;16(4):e0249688. Epub 2021 Apr 8.

Interdisciplinary Program in Precision Public Health, Korea University, Seoul, Republic of Korea.

Chronic rhinosinusitis (CRS) is characterized according to the presence or absence of nasal polyps (NPs) and displays nasal microbiota dysbiosis. However, optimal sampling methods of the nasal microbiome in CRS have not been identified. We aimed to assess the microbial composition in patients with CRS, comparing different sampling methods (swab and tissue biopsy), tissue types (uncinate tissue and NP), and disease subtypes. Samples were obtained by swabbing the middle meatus and taking a biopsy of uncinate tissue (UT) in patients with CRS with (CRSwNP, N = 8) or without NP (CRSsNP, N = 6) and controls (N = 8). NPs were also harvested in CRSwNP. DNAs were extracted from fifty-two samples and analyzed by 16S rRNA gene amplicon sequencing. As a result, a great interpersonal variance was observed in nasal swabs, while UT samples presented distinct microbiome with low inter-personal differences. Moreover, the UT microbiomes were further differentiated into three clusters which are associated with disease status (control, CRSsNP, and CRSwNP). Compared to UT, NP revealed a unique microbiome profile with significantly less bacterial diversity. Prevotella was the genus whose abundance was negatively correlated with disease severity in NP. In conclusion, tissue samples are better specimens than nasal swabs for assessing the microbiomes of CRS patients. Several bacteria in UT and NP tissues revealed an association with clinical severity of CRSwNP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249688PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031401PMC
April 2021

Crystal structure of the DNA-binding domain of Bacillus subtilis CssR.

Biochem Biophys Res Commun 2021 May 31;555:26-31. Epub 2021 Mar 31.

College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea. Electronic address:

Bacteria utilize two-component systems to regulate gene expression in response to changes in environmental stimuli. CssS/CssR, a two-component system in Bacillus subtilis, is responsible for overcoming envelope stresses caused by heat shock and secretion overload. During stress, the sensor component CssS is auto-phosphorylated and transfers the phosphoryl group to the response regulator CssR. Phosphorylated CssR then directly regulates the transcription of genes required to counteract the stress. Here, the crystal structure of the DNA-binding domain of CssR, determined at 1.07 Å resolution, is reported. The structure shows that the DNA-binding domain of CssR harbors a winged helix-turn-helix motif that is conserved in the OmpR/PhoB subfamily of response regulators. Based on the crystal structure, the dimeric architecture of the full-length CssR and its DNA-binding mode were suggested.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.101DOI Listing
May 2021

The complete mitochondrial genome information of (Amphibia, Anura, Ranidae) and the phylogenetic implication.

Mitochondrial DNA B Resour 2021 Mar 1;6(2):689-690. Epub 2021 Mar 1.

Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.

We determined the complete mitochondrial genome of (Anura: Ranidae) for the first time. The whole sequences were 17,370 bp and included 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. The gene arrangement was completely identical to those observed from other Ranidae species. We used 11 protein-coding genes to examine the phylogenetic placement of this species in the genus . was the closest sister species to . The clade of and formed a cluster with , which had a sister relationship with the group of , , and .
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http://dx.doi.org/10.1080/23802359.2021.1882896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928165PMC
March 2021

Water Adsorption Behavior on a Highly Dense Single-Walled Carbon Nanotube Film with an Enhanced Interstitial Space.

ACS Omega 2021 Mar 2;6(10):7015-7022. Epub 2021 Mar 2.

Carbon Materials Application Research Group, Korea Institute of Industrial Technology (KITECH), 222 Palbok-ro, Deokjin-gu, Jeonju 54853, Korea.

In this study, we describe the adsorption behavior of water (HO) in the interstitial space of single-walled carbon nanotubes (SWCNTs). A highly dense SWCNT (HD-SWCNT) film with a remarkably enhanced interstitial space was fabricated through mild HNO/HSO treatment. The N, CO, and H adsorption isotherm results indicated remarkably developed micropore volumes (from 0.10 to 0.40 mL g) and narrower micropore widths (from 1.5 to 0.9 nm) following mild HNO/HSO treatment, suggesting that the interstitial space was increased from the initial densely-packed network assembly structure of the SWCNTs. The HO adsorption isotherm of the HD-SWCNT film at 303 K showed an increase in HO adsorption (i.e., by ∼170%), which increased rapidly from the critical value of relative pressure (i.e., 0.3). Despite the remarkably enhanced adsorption capacity of HO, the rates of HO adsorption and desorption in the interstitial space did not change. This result shows an adsorption behavior different from that of the fast transport of HO molecules in the internal space of the SWCNTs. In addition, the adsorption capacities of N, CO, H, and HO molecules in the interstitial space of the HD-SWCNT film showed a linear relationship with the kinetic diameter, indicating an adsorption behavior that is highly dependent on the kinetic diameter.
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http://dx.doi.org/10.1021/acsomega.0c06302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970577PMC
March 2021

Posterior interosseous nerve syndrome caused by a ganglion cyst and its surgical release with intraoperative neurophysiological monitoring: A case report.

Medicine (Baltimore) 2021 Feb;100(8):e24702

Department of Orthopedic Surgery, Daegu Catholic University Hospital, Daegu, Republic of Korea.

Rationale: Intraoperative neurophysiological monitoring (IONM) has been utilized not only for the rapid detection of neural insults during surgeries, but also to verify the neurophysiological integrity of nerve lesions in the surgical field.

Patient Concerns: A 32-year-old woman presented with a wrist and finger drop that had lasted about 3 months.

Diagnoses: The result of the initial electrodiagnostic test was consistent with posterior interosseous nerve (PIN) syndrome. Ultrasonography and magnetic resonance imaging of the proximal forearm showed a cystic mass at the anterolateral aspect of the radial head, which was diagnosed as a ganglion cyst.

Interventions: Surgical release of the ganglion cyst with IONM was performed. During the surgery, we induced nerve action potentials and compound motor action potentials across the ganglion cyst, which demonstrated neural continuity.

Outcomes: Three months after the surgery, the patient showed partial recovery of wrist and finger extensor muscle power. An electrodiagnostic test conducted 3 months after the surgery showed reinnervation potentials in PIN-innervated muscles.

Lessons: IONM during peripheral nerve surgeries can support surgical decisions and confirm the location and degree of nerve damage.
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http://dx.doi.org/10.1097/MD.0000000000024702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909167PMC
February 2021

The Research Trends of Pharmacopuncture Therapy on Cervical Pain Caused by Traffic Accidents.

J Pharmacopuncture 2020 Dec;23(4):201-211

Kyunghee Dongju Korean Medicine Clinic, Seoul, Republic of Korea.

Objectives: The purpose of this study is to comprehensively review Korean domestic studies and investigate the research trends of pharmacopuncture therapy on cervical pain caused by traffic accidents.

Methods: Domestic studies between February 1999 and May 2020 from four Korean databases were searched with combinations of keywords 'cervical pain', 'traffic accident', 'whiplash injury', and 'pharmacopuncture'.

Results: 17 studies were selected for review, including 7 randomized controlled trials, 5 retrospective observational studies, 3 case reports, and 2 non-randomized controlled trials. Each study was reviewed by published year, study type, types of pharmacopuncture solutions, selected acupuncture points, dosage of pharmacopuncture solutions, frequency of treatment, concurrent treatments, outcome measurements, and the effectiveness of pharmacopuncture therapy. The results are as follows (1) It showed that the total number of published studies had increased slightly in the last 10 years compared to the previous decade. (2) The pharmacopuncture solutions used in the studies were in the following order Bee-Venom (), Jungsongouhyul (), Hwangryunhaedoktang () and Soyeom (). Frequently used acupuncture points were GB20, GV21, A-shi point, GV16, EX-B2, and SI15 in order. (3) The most commonly used total injection dosage was 1.0 cc at a time, and the frequency of treatment was twice a week. (4) Concurrent treatments such as acupuncture, herbal medication, physical therapy and Chuna manual therapy were performed in all 17 studies. (5) Pharmacopuncture therapy showed positive effects on cervical pain caused by traffic accidents in all 17 studies reviewed.

Conclusion: Pharmacopuncture therapy was effective in cervical pain caused by traffic accidents in all 17 studies selected. Further studies will be needed using more larger scales and more objective data to confirm the effectiveness of pharmacopuncture therapy and to generalize its application.
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http://dx.doi.org/10.3831/KPI.2020.23.4.201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772081PMC
December 2020

Flexible Carbon Nanotube/Polydimethylsiloxane Composite for the De-Icing of Airplane Wings.

J Nanosci Nanotechnol 2021 Mar;21(3):1779-1783

Department of Mechanical Engineering, Soongsil University, 369 Sangdo-ro, Donjak-gu, Seoul 156-743, Korea.

In the aviation industry, the process of de-icing is critical for stable flying because of the occurrence of airplane icing. To solve the icing problem, an electrical heating system is applied for airplane de-icing. Among the materials used in the electrical heating system, carbon-nanotube polymer composites are appropriate for an ice-prevention system owing to their rapid heating properties and flexibility. In this study, we fabricated a flexible carbon-nanotube/polydimethylsiloxane composite with a high content of carbon nanotube (20 wt%) for airplane de-icing. The high-load carbon nanotube composite was fabricated using a three-roll milling method, resulting in uniform dispersion of carbon nanotubes in the polymer matrix. The carbon nanotube/polydimethylsiloxane composites exhibited uniform and stable heating performance (from room temperature to 100 °C for 25 s without thermal aggregation). In addition, the carbon nanotube/polydimethylsiloxane composite is suitable for application to the curved surface of airfoils. For the de-icing experiments, a small airplane wing consisting of carbon nanotube/polydimethylsiloxane composite as a heating unit was fabricated with a scale ratio of 15:1. We conducted electrical heating and de-icing experiments using the developed airplane-wing system for actual anti-icing/de-icing applications.
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http://dx.doi.org/10.1166/jnn.2021.18933DOI Listing
March 2021

Voice outcomes after laryngeal microsurgery with adjunctive steroid injection for Reinke's edema.

Clin Exp Otorhinolaryngol 2020 Nov 27. Epub 2020 Nov 27.

Department of Otolaryngology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of Korea.

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http://dx.doi.org/10.21053/ceo.2020.01746DOI Listing
November 2020

Endogenous DEL-1 restrains melanoma lung metastasis by limiting myeloid cell-associated lung inflammation.

Sci Adv 2020 Nov 6;6(45). Epub 2020 Nov 6.

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

Distant metastasis represents the primary cause of cancer-associated death. Pulmonary metastasis is most frequently seen in many cancers, largely driven by lung inflammation. Components from primary tumor or recruited leukocytes are known to facilitate metastasis formation. However, contribution of target site-specific host factor to metastasis is poorly understood. Here, we show that developmental endothelial locus-1 (DEL-1), an anti-inflammatory factor abundant in the lung and down-regulated by inflammatory insults, protects from melanoma lung metastasis independently of primary tumor development and systemic immunosurveillance. DEL-1 deficiency is associated with gene profiles that favor metastatic progression with inflammation and defective immunosurveillance. Mechanistically, DEL-1 deficiency primarily influences Ly6G neutrophil accumulation in lung metastatic niche, leading to IL-17A up-regulation from γδ T cells and reduced antimetastatic NK cells. In support, neutrophil depletion or recombinant DEL-1 treatment profoundly reverses these effects. Thus, our results identify DEL-1 as a previously unrecognized link between tumor-induced inflammation and pulmonary metastasis.
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http://dx.doi.org/10.1126/sciadv.abc4882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673713PMC
November 2020

Correlation of site of obstruction between two dynamic evaluation modalities in obstructive sleep apnea patients: drug-induced sleep endoscopy and sleep videofluoroscopy.

Sleep Breath 2020 Oct 22. Epub 2020 Oct 22.

Department of Otorhinolaryngology-HNS, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Purpose: Drug-induced sleep endoscopy (DISE) and sleep videofluoroscopy (SVF) are two dynamic modalities for evaluating the upper airway in patients with obstructive sleep apnea (OSA). We evaluated the correlation of obstructive sites determined by DISE and SVF in OSA patients and elucidate findings that can improve the accuracy of upper airway assessment.

Methods: A consecutive series of 63 patients with OSA who underwent DISE and SVF were the subjects of this study. The DISE and SVF findings were divided according to the anatomical structure responsible for the collapse, including the soft palate (SP), oropharyngeal lateral walls (LW), tongue base (TB), and larynx (LX). The obstruction was graded on the three-point scale: 0, no obstruction; 1, partial obstruction; or 2, complete obstruction. Additionally, grade 1.5 TB obstruction was designated when the posterior displacement of the anterior tongue was detected during simultaneous retropalatal obstruction. The agreement rate and Cohen's kappa test between the two modalities were also assessed.

Results: The agreement rate between the two modalities was highest in LX (88.9%) followed by SP (85.7%), TB (76.1%), and LW (74.6%) (Cohen's kappa value = 0.757 in LX, 0.642 in SP, 0.637 in TB, 0.612 in LW, respectively). When grade 1.5 and 2 TB obstructions were combined, the agreement rate increased to 88.9% (Cohen's kappa value = 0.757).

Conclusions: We found a good overall agreement between the two dynamic airway evaluation modalities during drug-induced sleep, and this correlation may be improved if the posterior displacement of the anterior tongue during DISE is used as a sign of TB obstruction.
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http://dx.doi.org/10.1007/s11325-020-02225-8DOI Listing
October 2020

Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds.

Pharmaceutics 2020 Sep 28;12(10). Epub 2020 Sep 28.

College of Pharmacy, Pusan National University, Busan 46241, Korea.

Nitric oxide (NO), a highly reactive and lipophilic molecule, is one of the molecules present in the wound environment and implicated as an important regulator in all phases of wound healing. Here, we developed an NO-releasing thermoresponsive hydrogel (GSNO-PL/AL) composed of S-nitrosoglutathione (GSNO), pluronic F127 (PL), and alginate (AL) for the treatment of infected wounds. The GSNO was incorporated into the thermoresponsive PL/AL hydrogel, and differential scanning calorimetry techniques were used for the hydrogel characterization. The hydrogel was assessed by in vitro NO release, antibacterial activity, cytotoxicity, and wound-healing activity. The GSNO-PL/AL hydrogel demonstrated thermal responsiveness and biocompatibility, and it showed sustained NO release for 7 days. It also exhibited potent bactericidal activity against Gram-positive methicillin-resistant and Gram-negative multidrug-resistant (MRPA). Moreover, the GSNO-PL/AL treatment of MRPA-infected wounds accelerated healing with a reduced bacterial burden in the wounds. The GSNO-PL/AL hydrogel would be a promising option for the treatment of infected wounds.
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http://dx.doi.org/10.3390/pharmaceutics12100926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600256PMC
September 2020

Angiotensin AT receptor antagonism by losartan stimulates adipocyte browning via induction of apelin.

J Biol Chem 2020 10 24;295(44):14878-14892. Epub 2020 Aug 24.

Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, Republic of Korea; Department of Pharmacology, College of Medicine, Gachon University, Incheon, Republic of Korea. Electronic address:

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT receptor) signaling. Here, we report that losartan, a selective AT receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.
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http://dx.doi.org/10.1074/jbc.RA120.013834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606681PMC
October 2020

Double-Blind Placebo-Controlled Trial of Bepotastine Salicylate in Patients With Allergic Rhinitis.

Laryngoscope 2021 03 31;131(3):E702-E709. Epub 2020 Jul 31.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.

Objectives/hypothesis: To evaluate the efficacy and safety of a slow-release form of bepotastine salicylate (HL151, Belion CR) in patients with perennial allergic rhinitis (PAR).

Study Design: Double-blind, placebo-controlled multicenter comparative study.

Methods: Two hundred seventy-two PAR patients (aged 19-65 years) were studied to determine the efficacy and safety of HL151 (20 mg once daily administration) relative to those of a placebo in terms of improvements in total and nasal symptom scores. The subjects were randomized to the placebo (n = 138) or HL151 group (n = 134, 20 mg orally once daily for 4 weeks), and reflective and instantaneous total nasal symptom scores (TNSS) were measured daily in comparison with baseline. Among 272 subjects, 229 subjects (119 in the placebo group, 110 in the HL151 group) who completed the study were included for efficacy analysis.

Results: Instantaneous and reflective TNSS and nasal symptoms such as rhinorrhea, nasal itching, and sneezing at 2 and 4 weeks showed that HL151 was superior to the placebo (all P < .05). There were no significant differences in terms of adverse events and adverse drug reactions between the two groups. Regarding serious adverse events, there was only one case of acute hepatitis B, which was reported not to be associated with HL151.

Conclusions: This multicenter trial showed that once-daily use of HL151 is efficacious and safe in adult patients with PAR and could improve compliance due to its convenience.

Level Of Evidence: 1b Laryngoscope, 131:E702-E709, 2021.
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http://dx.doi.org/10.1002/lary.28906DOI Listing
March 2021

Structural insights into the regulation of SigB activity by RsbV and RsbW.

IUCrJ 2020 Jul 24;7(Pt 4):737-747. Epub 2020 Jun 24.

College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.

SigB is an alternative sigma factor that initiates the transcription of stress-responsive genes. The anti-sigma factor RsbW tightly binds SigB to suppress its activity under normal growth conditions and releases it when nonphosphorylated RsbV binds to RsbW in response to stress signals. To understand the regulation of SigB activity by RsbV and RsbW based on structural features, crystal structures and a small-angle X-ray scattering (SAXS) envelope structure of the RsbV-RsbW complex were determined. The crystal structures showed that RsbV and RsbW form a heterotetramer in a similar manner to a SpoIIAA-SpoIIAB tetramer. Multi-angle light scattering and SAXS revealed that the RsbV-RsbW complex is an octamer in solution. Superimposition of the crystal structure on the SAXS envelope structure showed that the unique dimeric interface of RsbW mediates the formation of an RsbV-RsbW octamer and does not prevent RsbV and SigB from binding to RsbW. These results provide structural insights into the molecular assembly of the RsbV-RsbW complex and the regulation of SigB activity.
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http://dx.doi.org/10.1107/S2052252520007617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340262PMC
July 2020

Selective interactions between mimivirus uracil-DNA glycosylase and inhibitory proteins determined by a single amino acid.

J Struct Biol 2020 09 19;211(3):107552. Epub 2020 Jun 19.

College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, South Korea. Electronic address:

Uracil-N-glycosylase (UNG) is found in most organisms as well as in large DNA viruses. Its inhibitory proteins, including uracil glycosylase inhibitor (UGI) and p56, tightly bind to the active site of UNG by mimicking the DNA substrates. As the binding motifs are conserved in UNG family proteins, the inhibitory proteins bind to various UNG proteins across species. However, the intercalation residue that penetrates the DNA minor groove during uracil excision is not conserved among UNG proteins. To understand the role of the intercalation residue in their binding to the inhibitory proteins, we prepared mutants of mimivirus UNG, measured the binding affinity between the UNG mutants and inhibitory proteins, and analyzed the interactions based on the crystal structures of mimivirus UNG mutants complexed with UGI. The results show that mimivirus UNG, which harbors Tyr as an intercalation residue, did not interact with the inhibitory proteins intrinsically, whereas mutations of the intercalation residue to Phe or Leu resulted in tight interactions with UGI and p56; mutation to Met resulted in tight interactions only with p56. The crystal structures revealed that Phe and Leu stabilize the interactions by fitting into the hydrophobic pocket of UGI. These results show that differences in size and hydrophobicity of the intercalation residues determine the interactions between UNG family proteins and the inhibitory proteins, UGI and p56.
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http://dx.doi.org/10.1016/j.jsb.2020.107552DOI Listing
September 2020

House Dust Mite Sublingual Immunotherapy in Children Versus Adults With Allergic Rhinitis.

Am J Rhinol Allergy 2021 Jan 13;35(1):9-16. Epub 2020 Jun 13.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.

Background: There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL).

Objective: To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events.

Methods: Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26).

Results: The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups (, both); however, changes in TNSS from baseline did not significantly differ between the two groups (). More patients in adult group were satisfied with SLIT than those in child group (), and changes in RQLQ score from baseline tended to be larger in adult group (). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different.

Conclusion: Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.
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http://dx.doi.org/10.1177/1945892420931713DOI Listing
January 2021

CU06-1004 (endothelial dysfunction blocker) ameliorates astrocyte end-feet swelling by stabilizing endothelial cell junctions in cerebral ischemia/reperfusion injury.

J Mol Med (Berl) 2020 06 16;98(6):875-886. Epub 2020 May 16.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Cerebral ischemia, or stroke, is widespread leading cause of death and disability. Surgical and pharmacological interventions that recover blood flow are the most effective treatment strategies for stroke patients. However, restoring the blood supply is accompanied by severe reperfusion injury, with edema and astrocyte end-feet disruption. Here, we report that the oral administration of CU06-1004 (previously Sac-1004), immediately after onset of ischemia/reperfusion (I/R), ameliorated cerebral damage. CU06-1004 stabilized blood‑brain barrier by inhibiting the disruption of the tight junction-related protein zona occludens-1 and the cortical actin ring in endothelial cells (ECs) after I/R. Interestingly, CU06-1004 significantly suppressed astrocyte end-feet swelling following I/R, by reducing aquaporin 4 and connexin 43 levels, which mediates swelling. Furthermore, the degradation of β1-integrin and β-dystroglycan, which anchors to the cortical actin ring in ECs, was inhibited by CU06-1004 administration after I/R. Consistently, CU06-1004 administration following I/R also suppressed the loss of laminin and collagen type IV, which bind to the cortical actin ring anchoring proteins. Unlike the protective effects of CU06-1004 in ECs, astrocyte viability and proliferation were not directly affected. Taken together, our observations suggest that CU06-1004 inhibits I/R-induced cerebral edema and astrocyte end-feet swelling by maintaining EC junction stability. KEY MESSAGES: • CU06-1004 ameliorates I/R-induced cerebral injury. • EC junction integrity was stabilized by CU06-1004 treatment after I/R. • CU06-1004 reduces astrocyte end-feet swelling following I/R. • EC junction stability affects astrocyte end-feet structure maintenance after I/R.
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http://dx.doi.org/10.1007/s00109-020-01920-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297708PMC
June 2020

Characteristics of Obstructive Sleep Apnea Patients With a Low Body Mass Index: Emphasis on the Obstruction Site Determined by Drug-Induced Sleep Endoscopy.

Clin Exp Otorhinolaryngol 2020 Nov 29;13(4):415-421. Epub 2020 Apr 29.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Objectives: This study aimed to elucidate the patterns of upper airway collapse in obstructive sleep apnea (OSA) patients with a low body mass index (BMI).

Methods: We designed and conducted a retrospective cohort study. Consecutive patients diagnosed with OSA who underwent drug-induced sleep endoscopy (DISE) were included. Patients were classified into four groups according to their BMI. Age, sex, and polysomnography data were investigated. The patterns of upper airway collapse were characterized by the structures involved (soft palate, tongue base, lateral pharyngeal wall, and epiglottis). We compared the patterns of upper airway collapse in the supine and lateral decubitus position among the four BMI groups using the chi-square test and multivariate binary logistic regression analysis.

Results: A total of 627 patients (male, 517; mean age, 47.6±12.8 years) were included, consisting of 45, 79, 151, and 352 patients who were underweight or lower normal-weight (defined as the low BMI group), upper normal-weight, overweight, and obese, respectively. Severity indicators of OSA, such as the overall apnea-hypopnea index and duration of SaO2 below 90%, were significantly lower in patients with a low BMI than in obese patients, while their average oxygen saturation was significantly higher. The most common obstruction site in the supine position was the tongue base in patients with a low BMI (100%), whereas this obstruction site was significantly less common in obese patients (54.8%). Tongue base obstruction was mostly relieved in the lateral position, with no discernible obstruction in 86.7% of the low BMI patients.

Conclusion: Airway obstruction in OSA patients with a low BMI is mostly due to tongue base obstruction, which improves in the lateral position. These characteristics should be kept in mind when considering treatment options for this subgroup of OSA patients.
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http://dx.doi.org/10.21053/ceo.2019.00794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669311PMC
November 2020

Wnt-PLC-IP-Connexin-Ca axis maintains ependymal motile cilia in zebrafish spinal cord.

Nat Commun 2020 04 20;11(1):1860. Epub 2020 Apr 20.

Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea.

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.
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http://dx.doi.org/10.1038/s41467-020-15248-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170879PMC
April 2020

Time-gated iterative phase conjugation for efficient light energy delivery in scattering media.

Opt Express 2020 Mar;28(5):7382-7391

Light waves propagating through complex biological tissues are spatially spread by multiple light scattering, and this spread limits the working depth in optical bioimaging, phototherapy, and optogenetics. Here, we propose the iterative phase conjugation of time-gated backscattered waves for enhancing the light energy delivered to a target object embedded in a scattering medium. We demonstrate the enhancement of light energy delivered to a target object hidden behind a 200-µm-thick mouse skull by more than ten times in comparison with the initial random input. The maximum enhancement was reached in only 10 iterations, more than a hundred times smaller than existing methods based on either a time-gated reflection matrix or iterative feedback optimization of the time-gated reflection intensity. Consequently, the proposed method is less sensitive to sample perturbations. Furthermore, the number of images required for optimization remained almost unchanged with an increase in the illumination area, unlike existing methods, where the convergence time scales with the illumination area. The proposed method provides high operation speed over a wide illumination area, which can facilitate the use of wavefront shaping in practical applications.
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http://dx.doi.org/10.1364/OE.385557DOI Listing
March 2020

Osteogenesis imperfecta and combined orthodontics and orthognathic surgery: a case report on two siblings.

J Korean Assoc Oral Maxillofac Surg 2020 Feb 26;46(1):70-77. Epub 2020 Feb 26.

Department of Oral and Maxillofacial Surgery, Asan Medical Center, Seoul, Korea.

Osteogenesis imperfecta is a heterogeneous group of connective tissue diseases that is predominantly characterized by bone fragility and skeletal deformity. Two siblings with undiagnosed type I osteogenesis imperfecta underwent orthognathic surgery for the treatment of facial asymmetry and mandibular prognathism. The authors report two cases of combined orthodontics and orthognathic surgery in patients with type I osteogenesis imperfecta, mandibular prognathism, and facial asymmetry.
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http://dx.doi.org/10.5125/jkaoms.2020.46.1.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049766PMC
February 2020

Relationship between Sleep Duration, Sun Exposure, and Serum 25-Hydroxyvitamin D Status: A Cross-sectional Study.

Sci Rep 2020 03 6;10(1):4168. Epub 2020 Mar 6.

Department of Otolaryngology, Ajou University School of Medicine, Suwon, Republic of Korea.

Normal-range sleep duration is an important factor for general health and metabolism, and insufficient or excessive sleep is associated with chronic metabolic disease. Among the many factors that affect sleep duration, sun exposure plays an important role in maintaining regular circadian rhythm and is also involved in the production and activation of 25-hydroxyvitamin D [25(OH)D], which regulates various functions in the body. However, 25(OH)D is available through food and various nutritional supplements without sun exposure, so it is important to find out the complex relationship among sun exposure, vitamin D status, and sleep duration. The relationship between sun exposure, vitamin D status, and sleep duration was analyzed in the nationwide survey and examination of 25,534 study populations, after adjusting for demographic characteristics, physical characteristics, lifestyle status, and socio-demographic variables. Vitamin D status alone did not show the relationship with sleep duration, although there were statistical relationships in the various factors including sun exposure with sleep duration. There was a statistical difference in 25(OH)D according to sleep duration, only in low sun exposure group. Subjects with low sun exposure and excessive sleep duration comparatively lower 25(OH)D than those with normal-range sleep, even after adjustment for potentially confounding factors. Individuals with limited exposure to sunlight should maintain adequate vitamin D status to have an appropriate sleep duration for health.
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http://dx.doi.org/10.1038/s41598-020-61061-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060268PMC
March 2020