• 한국균학회지
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• 제49권4호
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• pp.487-495
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• 2021

표고는 사극성의 교배계를 갖는 담자균의 일종으로, 표고의 교배형은 A와 B라 불리는 서로 독립된 두 유전자좌에 의해 결정된다. 이론적으로 하나의 이핵균주는 네 개의 서로 다른 교배형을 갖는 담자포자를 1:1:1:1의 비율로 만들 수 있다. 과거 연구 결과에 따르면, 표고 담자포자에서 교배형이 편향된 분리비로 나타남이 보고되었다. 하지만 이러한 결과들은 꺽쇠연결과 같은 형태학적 특성만을 기반으로 교배형을 결정했다는 한계가 있다. 이에 본 연구에서는 교배형의 편향된 분리비가 표고에서 일반적인 현상인지 보다 명확하게 알아보기 위해서 최근에 보고된 DNA 마커를 활용하여 세 가지 표고 품종들의 담자포자에 대한 교배형 분석을 수행하였다. 그 결과 교배형의 편향된 분리비가 과거 보고와 일치하게 균주 특이적인 특성임을 확인하였다. 분석한 세 품종 중 한 품종을 제외하고 나머지 두 품종에서 편향된 분리비가 관찰된 것이다. 다음으로는 각 담자포자 유래 단핵균사들의 생장 속도와 교배형의 상관관계를 분석하였다. 그 결과 표고 단핵균사의 생장 속도는 B 교배형과는 관계가 없고, A 교배형과 관계가 있음을 확인하였다. 따라서 A 교배형 유전자좌에 존재하는 호메오도메인 전사인자 혹은 A 교배형 유전자좌와 연관된 유전자들이 단핵균사의 생장에 영향을 줄 것으로 보인다. 버섯 신품종 육성에서 교배형의 중요성을 고려할 때, 본 연구는 효율적인 신품종 육성 전략을 세우거나 단핵균사 생장 기작을 이해하는 데 도움을 줄 것으로 기대된다.

• Composites Research
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• 제34권1호
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• pp.8-15
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• 2021

조선해양 산업에서 선박의 에너지 절감과 운항효율 향상을 위한 부품의 경량화 기술이 요구됨에 따라서, 고강도의 경량소재인 섬유강화 복합소재를 부품소재로 적용하는 방안이 검토될 수 있다. 본 연구에서는 LNGC 경량화를 위해 파이프 지지용 클램프의 섬유강화 복합소재 적용 가능성을 평가하였다. 탄소섬유 및 유리섬유를 강화섬유로 하여 섬유강화 복합소재를 제조하였으며, 컴퓨터 시뮬레이션 프로그램을 통해 복합소재의 강화재료와 기지재료의 물성을 역계산하여 섬유 적층 패턴별 물성 변화에 따른 성능 예측을 수행하였다. 또한, 유한요소해석 프로그램를 통해 복합소재 두께에 따른 클램프의 구조해석을 수행하였다. 연구결과 경량화를 위해 클램프의 섬유강화 복합소재의 적용시 두께 선정에 주의가 필요함을 확인할 수 있었다. 향후 보완 설계 시 구조물의 형상변경 및 경량화를 위한 구조변경에 용이할 것으로 판단된다.

• 대한족부족관절학회지
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• 제26권2호
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• pp.95-102
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• 2022

Purpose: This study was based on the Korean Foot and Ankle Society (KFAS) member survey and aimed to report the current trends in the management of syndesmotic injuries over the last few decades. Materials and Methods: A web-based questionnaire containing 36 questions was sent to all KFAS members in September 2021. The questions were mainly related to the preferred techniques and clinical experiences in the treatment of patients with syndesmotic injuries. Answers with a prevalence ≥50% of respondents were considered a tendency. Results: Seventy-six (13.8%) of the 550 members responded to the survey. The results showed that the most preferred method to diagnose a syndesmotic injury was magnetic resonance imaging (MRI). Intraoperatively, the external rotation stress test and the Cotton test were most frequently used to confirm syndesmotic diastasis. The reduction was usually done by a reduction clamp. One 3.5-mm screw was used most frequently over three cortices at 2~4 cm above the ankle joint. The preferred ankle position during fixation was 0° dorsiflexion. Removal of the syndesmotic screw was routinely done by most surgeons, mainly because of the limitation of movement and risk of screw breakage. Factors that affect suture button selection included non-rigid fixation which enables adequate fixation, early weight-bearing, and an infrequent need to remove the hardware. Inadequate reduction was considered the main factor that affects poor prognosis. Conclusion: This study proposes updated information about the current trends in the management of syndesmotic injuries in Korea. Consensuses in both the diagnostic and therapeutic approach to patients with syndesmotic injury were identified in this survey study. This study may raise the awareness of the various possible approaches toward the injury and should be used to further establish a standard protocol for the management of syndesmotic injuries.

• 대한한의학방제학회지
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• 제30권2호
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• pp.37-44
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• 2022

Objectives : The purpose of this study was to examine the effects of Alisma canaliculatum Extract (ACE) on pacemaker potentials of small and large intestinal interstitial Cells of Cajal (ICC) in mice. Methods : We used enzymatic digestions to dissociate the ICC in the small and large intestine in mice. The whole-cell patch-clamp method was used to record pacemaker potentials in ICC. Results : 1. The ICC generated the pacemaker potentials in small intestine in mice. ACE (0.1-1mg/ml) induced membrane depolarization and decreased frequency with concentration-dependent manners. 2. Pretreatment with a Ca²⁺ free solution, Na⁺ 5 mM solution or 2-APB, a nonselective cation channel blocker, stopped the small intestinal ICC pacemaker potentials. In the case of Ca²⁺-free solution, Na⁺ 5 mM solution or 2-APB, ACE had no effects on the membrane depolarizations in small intestinal ICC. 3. The ICC generated the pacemaker potentials in large intestine in mice. Membrane depolarization appears regularly in the small intestine, but irregularly in the large intestine. ACE induced membrane depolarization (0.1-1mg/ml) and increased frequency (0.1-0.5mg/ml). 4. Pretreatment with a Ca²⁺ free solution, Na⁺ 5 mM solution or 2-APB, stopped the large intestinal ICC pacemaker potentials. In the case of Ca²⁺-free solution, Na⁺ 5 mM solution or 2-APB, ACE depolarized the membrane depolarizations in large intestinal ICC. 5. In mice, intestinal transit rate (ITR) values were dose-dependently decreased by the intragastric administration of ACE. Conclusions : These results suggest that ACE can regulate the pacemaker activity of ICC and the reaction by ACE is different from the small and large intestinal ICC, and the control of the intestinal motion by ACE may be caused by many complex processes.

• The Korean Journal of Physiology and Pharmacology
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• 제26권5호
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• pp.313-323
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• 2022

Atrial fibrillation (AF) is the most common supraventricular arrhythmia, and it corresponds highly with exercise intensity. Here, we induced AF in mice using acetylcholine (ACh)-CaCl₂ for 7 days and aimed to determine the appropriate exercise intensity (no, low, moderate, high) to protect against AF by running the mice at different intensities for 4 weeks before the AF induction by ACh-CaCl₂. We examined the AF-induced atrial remodeling using electrocardiogram, patch-clamp, and immunohistochemistry. After the AF induction, heart rate, % increase of heart rate, and heart weight/body weight ratio were significantly higher in all the four AF groups than in the normal control; highest in the high-ex AF and lowest in the low-ex (lower than the no-ex AF), which indicates that low-ex treated the AF. Consistent with these changes, G protein-gated inwardly rectifying K⁺ currents, which were induced by ACh, increased in an exercise intensity-dependent manner and were lower in the low-ex AF than the no-ex AF. The peak level of Ca²⁺ current (at 0 mV) increased also in an exercise intensity-dependent manner and the inactivation time constants were shorter in all AF groups except for the low-ex AF group, in which the time constant was similar to that of the control. Finally, action potential duration was shorter in all the four AF groups than in the normal control; shortest in the high-ex AF and longest in the low-ex AF. Taken together, we conclude that low-intensity exercise protects the heart from AF, whereas high-intensity exercise might exacerbate AF.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.267-275
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• 2023

Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of I_Kr and I_Na currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of I_Kr and I_Ca currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of I_Ca currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

• The Korean Journal of Physiology and Pharmacology
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• 제27권6호
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• 생명과학회지
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• 제34권1호
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• pp.1-8
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• 2024

Brain-type natriuretic peptide (BNP)은 뇌나트륨이뇨펩티드로, 좌심실의 심근세포에서 분비되는 호르몬으로, 심장과 신장에 작용하여 혈관 확장과 나트륨 이뇨 작용 등을 하는 것으로 알려져 있으나, 최근에는 다양한 조직에서 대사 작용을 조절하는 것으로 보고된다. 본 연구에서는 간 조직에서 BNP의 영향을 알기 위해 BNP가 고지방식이에 의해 유도되는 인슐린 저항성을 개선하는지를 조사하였다. BNP을 주입한 쥐와 control로서 saline을 주입한 쥐들 간에는 몸무게, 체지방양(fat mass), 제지방량(lean body mass)의 변화는 없었다. 고인슐린혈증 정상혈당 글루코스 클램프(Hyperinsulinemic Euglycemic Glucose Clam) 동안, BNP를 주입한 고지방 식이 쥐들은 saline을 주입한 고지방식이 쥐에 비해 혈당(blood glucose)은 감소하였으며, 포도당 주입 속도(glucose infusion rate)는 증가하였다. 또한 BNP은 포도당 신생 및 중성지방 합성 관련 유전자들의 발현을 감소시켜, 간에서 포도당 생성과 중성지방의 양을 감소시켰다. BNP는 saline을 주입한 쥐에 비해 간 조직에서 Akt와 AMP-activated protein kinase (AMPK)의 인산화를 증가시켰는데, 이는 BNP을 처리한 AML12 간세포에서도 BNP는Akt와 AMPK 인산화를 증가시켰다. 이상의 결과는 BNP가 간에서 인슐린 저항성을 개선하여 포도당 생성과 중성 지방 생성을 억제함을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.313-322
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• 2024

Mutations within the SCN5A gene, which encodes the α-subunit 5 (Na_V1.5) of the voltage-gated Na⁺ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the Na_V1.5 current (I_Na) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of I_Na was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the co-expression of SCN1B with p.A385T/R504T revealed significant reduction of I_Na and slower recovery from inactivation, consistent with the loss-of-function in Na⁺ channels. The SCN1B dependent reduction of I_Na was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of Na_V1.5, respectively.

• International Journal of Stem Cells
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• 제15권3호
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• pp.247-257
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• 2022

Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions: Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our understanding of the importance of RA signaling in the differentiation of hiPSC-CMs.