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Lee, Seahyoung,Yun, Ina,Ham, Onju,Lee, Se-Yeon,Lee, Chang Yeon,Park, Jun-Hee,Lee, Jiyun,Seo, Hyang-Hee,Choi, Eunhyun,Hwang, Ki-Chul BioMed Central 2015 BIOLOGICAL RESEARCH Vol.48 No.1
<P><B>Background</B></P><P>Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H<SUB>2</SUB>O<SUB>2</SUB>. The expression of HKII in MSCs exposed to H<SUB>2</SUB>O<SUB>2</SUB> was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H<SUB>2</SUB>O<SUB>2</SUB> on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H<SUB>2</SUB>O<SUB>2</SUB>-induced apoptosis of MSC was evaluated.</P><P><B>Results</B></P><P>H<SUB>2</SUB>O<SUB>2</SUB> (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H<SUB>2</SUB>O<SUB>2</SUB> increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H<SUB>2</SUB>O<SUB>2</SUB>-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H<SUB>2</SUB>O<SUB>2</SUB>.</P><P><B>Conclusions</B></P><P>These findings suggest that H<SUB>2</SUB>O<SUB>2</SUB>-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.</P>
Lee, Jung-Kyu,Lee, Ji Yeon,Kim, Deog Kyeom,Yoon, Ho Il,Jeong, Ina,Heo, Eun Young,Park, Young Sik,Jo, Yong Suk,Lee, Jae Ho,Park, Sung Soo,Park, Jong Sun,Kim, Junghyun,Lee, Sang-Min,Joh, Joon-Sung,Lee, Elsevier 2019 LANCET INFECTIOUS DISEASES Vol.19 No.1
<P><B>Summary</B></P> <P><B>Background</B></P> <P>Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis.</P> <P><B>Methods</B></P> <P>We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460.</P> <P><B>Findings</B></P> <P>Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient.</P> <P><B>Interpretation</B></P> <P>Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis.</P> <P><B>Funding</B></P> <P>Ministry of Health and Welfare, South Korea.</P>
Lee, Minji,Kim, Jong Hyun,Yoon, Ina,Lee, Chulho,Fallahi Sichani, Mohammad,Kang, Jong Soon,Kang, Jeonghyun,Guo, Min,Lee, Kang Young,Han, Gyoonhee,Kim, Sunghoon,Han, Jung Min National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.23
<P>A protein synthesis enzyme, leucyl-tRNA synthetase (LRS), serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which is a central effector for protein synthesis, metabolism, autophagy, and cell growth. However, its significance in mTORC1 signaling and cancer growth and its functional relationship with other suggested leucine signal mediators are not well-understood. Here we show the kinetics of the Rag GTPase cycle during leucine signaling and that LRS serves as an initiating 'ON' switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an 'OFF' switch by controlling GTP hydrolysis of RagB in the Rag GTPase-mTORC1 axis. The LRS-RagD axis showed a positive correlation with mTORC1 activity in cancer tissues and cells. The GTP-GDP cycle of the RagD-RagB pair, rather than the RagC-RagA pair, is critical for leucine-induced mTORC1 activation. The active RagD-RagB pair can overcome the absence of the RagC-RagA pair, but the opposite is not the case. This work suggests that the GTPase cycle of RagD-RagB coordinated by LRS and Sestrin2 is critical for controlling mTORC1 activation, and thus will extend the current understanding of the amino acidsensing mechanism.</P>
Two new species of the tribe Hymenaphorurini Pomorski, 1996 (Collembola: Onychiuridae) from Korea
Lee Inae,박경화 한국응용곤충학회 2021 Journal of Asia-Pacific Entomology Vol.24 No.1
Two new species, Heteraphorura koreana sp. nov. and Psyllaphorura jirisana sp. nov., of the tribe Hymena phorurini are described and illustrated based on materials from South Korea. Heteraphorura koreana sp. nov. belongs to the oriental species-group of the genus Heteraphorura, because of compound vesicles in the post antennal organ. This new species shares the same number of PAO with Heteraphorura pseudoseolagensis (Mar tynova, 1981) from Russia, but differs in pso dorsal formula and lateral teeth of claw. Psyllaphorura jirisana sp. nov. is similar to Psyllaphorura sensillifera.
Lee, Inae,Park, Chan Woo,Yoon, Seung Soo,Yang, Hee-Man Elsevier 2019 CHEMOSPHERE - Vol.224 No.-
<P><B>Abstract</B></P> <P>A simple one-step approach for fabricating copper ferrocyanide-embedded magnetic hydrogel beads (CuFC-MHBs) was designed, and the beads were applied to the effective removal of cesium (Cs) and then magnetically separated from water. The polyvinyl alcohol (PVA)-coated CuFC (PVA-CuFC) was first synthesized using PVA as a stabilizer and subsequently embedded in magnetic hydrogel beads made of a cross-linked network between the PVA and magnetic iron oxide nanoparticles that was prepared through the simple dropwise addition of a mixed solution of PVA-CuFC, PVA and iron salt into an ammonium hydroxide solution. The synthesis and chemical immobilization of the PVA-CuFC in the magnetic beads were simple, facile and achieved in one pot, and the process is scalable and convenient for the large-scale treatment of Cs-contaminated water. The resulting CuFC-MHBs showed effective Cs removal performance with a high K<SUB>d</SUB> value of 66,780 mL/g and excellent structural stability without the release of CuFC for at least 1 month and could be effectively separated from water by an external magnet. Moreover, the CuFC-MHBs selectively adsorbed Cs with high K<SUB>d</SUB> values in the presence of various competing ions, such as in simulated groundwater (24,500 mL/g) and seawater (8290 mL/g), and maintained their Cs absorption ability in a wide pH range from 3 to 11. The convenient fabrication method and effective removal of Cs from various aqueous media demonstrated that the CuFC-MHBs have great potential for practical application in the decontamination of Cs-contaminated water sources caused by nuclear accidents and radioactive liquid waste in various nuclear industry fields.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A facile one-pot synthesis of copper-ferrocyanide-embedded magnetic hydrogel beads was developed. </LI> <LI> CuFC-MHBs can be fabricated in a large quantity, which is crucial for their practical applications. </LI> <LI> The beads can remove Cs in a wide pH range from 3 to 11 with excellent structural stability for up to 1 month. </LI> <LI> The beads exhibit excellent selectivity for Cs, even in the presence of competing ions such as in groundwater conditions. </LI> </UL> </P>