Suppression of miR-181a attenuates H ₂ O ₂ -induced death of mesenchymal stem cells by maintaining hexokinase II expression

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>

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial

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>

Association of urinary phthalate metabolites and phenolics with adipokines and insulin resistance related markers among women of reproductive age

Lee, Inae,Kim, Sunmi,Park, Suhyeon,Mok, Sori,Jeong, Yunsun,Moon, Hyo-Bang,Lee, Jangwoo,Kim, Sungkyoon,Kim, Hai-Joong,Choi, Gyuyeon,Choi, Sooran,Kim, Su Young,Lee, Aram,Park, Jeongim,Choi, Kyungho Elsevier BV 2019 Science of the Total Environment Vol.688 No.-

<P><B>Abstract</B></P> <P>Chemicals such as phthalates and phenolics have been associated with metabolic markers in humans. However, most studies have only looked at a limited number of chemicals, and little is known about their potential effects on adipokines in humans. In the present study, the associations between dozens of urinary chemicals, including phthalate metabolites and phenolics, and markers related to insulin resistance as well as major adipokines, were assessed among the women of reproductive age (<I>n</I> = 459, between 20 and 48 years of age) recruited from major cities in Korea between 2015 and 2016. Adipokines such as adiponectin and leptin, and insulin resistance related markers such as glucose and insulin, were analyzed in serum. Associations between urinary chemicals and the adipokines or insulin resistance related markers were assessed in two steps. First, ordinary least squares (OLS) regression was used to assess the association of each urinary chemical with the adipokines or insulin resistance related markers (single-pollutant model). Second, several chemicals were selected using elastic net regression and were subsequently analyzed with OLS regression model (multi-pollutant model), considering simultaneous exposure to multiple chemicals. In both single- and multi-pollutant models, several urinary chemicals consistently showed significant associations with adipokines or the insulin resistance related markers. The sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) and ethyl paraben (EtP) were associated with increased serum adiponectin levels. Urinary ΣDEHPm levels also showed positive associations with fasting glucose. Moreover, urinary mono-methyl phthalate (MMP), mono-isobutyl phthalate (MiBP), and bisphenol S (BPS) levels showed positive associations with the homeostasis model assessment for insulin resistance (HOMA-IR). Interestingly, urinary propyl paraben (PrP) levels showed a negative association with HOMA-IR, in both models. Our observations show that among many consumer chemicals, phthalates may affect serum adipokines, and thus glucose, and insulin resistance in adult females. Further confirmation is warranted in other populations.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Urinary chemicals and metabolism related markers were measured in women of reproductive age. </LI> <LI> Multiple chemicals were considered in statistical models for adipokines and insulin resistance. </LI> <LI> Sum of DEHP metabolites and EtP were positively associated with serum adiponectin levels. </LI> <LI> Sum of DEHP metabolites was significantly associated with increased fasting glucose. </LI> <LI> MiBP was significantly associated with for increased HOMA-IR. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Sandaracinobacter neustonicus sp. nov., isolated from the sea surface microlayer in the Southwestern Pacific Ocean, and emended description of the genus Sandaracinobacter

Lee, Inae,Lee, Yung Mi,Rhee, Tae Siek 극지연구소 2021 극지연구소 초록집 Vol.- No.-

Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway

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>

Pseudomonas neustonica sp. nov., isolated from the sea surface microlayer of the Ross Sea (Antarctica)

Lee, Inae,Hwang, Yeon Ju,Yun, Sukyoung,Lee, Won Sang 극지연구소 2021 극지연구소 초록집 Vol.- No.-

Urinary phthalate metabolites among children in Saudi Arabia: Occurrences, risks, and their association with oxidative stress markers

Lee, Inae,Alakeel, Raid,Kim, Sungmin,Al-Sheikh, Yazeed A.,Al-Mandeel, Hazem,Alyousef, Abdullah A.,Kho, Younglim,Choi, Kyungho Elsevier BV 2019 Science of the Total Environment Vol.654 No.-

<P><B>Abstract</B></P> <P>Phthalates have been used as plasticizers in numerous consumer applications and therefore, their metabolites have been detected in human urine worldwide. Despite concerns regarding their potential adverse health effects, few exposure assessments have been conducted among young populations in Middle Eastern countries. In this study, children (n = 109, aged 3–9 years) were recruited from four elementary schools in Riyadh, Saudi Arabia, in 2017, and major phthalate metabolites were measured in their urine. Their parents were asked to complete a questionnaire on their behalf to assess potential exposure sources of phthalates. In addition to 18 phthalate metabolites, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured in urine samples by LC/MS/MS. Among the children of Saudi Arabia, urinary levels of monoisobutyl phthalate (MiBP) and monobutyl phthalate (MnBP) were higher than those reported previously in children worldwide. Monoethyl phthalate (MEP) was also detected at high levels. Several phthalate metabolites showed significant associations with the levels of MDA or 8-OHdG. Hazard quotients (HQs) derived for certain phthalates were greater than one. In particular, the HQs for di(2-ethylhexyl) phthalate (DEHP) were greater than one in 34% of the participating children. Levels of monocyclohexyl phthalate (MCHP), monoisodecyl phthalate (MiDP), mono(2-ethylhexyl) phthalate (MEHP), and mono[2-(carboxymethyl)hexyl] phthalate (MCMHP) in the urine samples were positively associated with the consumption frequency of certain foods. Very high levels of exposure to phthalates, along with positive associations with oxidative stress markers, outline the importance of follow-up investigations for identification of phthalate exposure sources and potential health implications among the young population of Saudi Arabia.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Eighteen phthalate metabolites were analyzed in urine samples from Saudi Arabian children. </LI> <LI> MiBP and MnBP were detected at higher levels than those reported in other countries. </LI> <LI> Approximately 34% of the children showed potential risks (HQ > 1) from DEHP exposure. </LI> <LI> Certain phthalate metabolites were associated with oxidative stress markers. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Sandaracinobacter neustonicus sp. nov., isolated from the sea surface microlayer in the Southwestern Pacific Ocean, and emended description of the genus Sandaracinobacter

Lee, Inae,Lee, Yung Mi,Rhee, Tae Siek 극지연구소 2021 극지연구소 초록집 Vol.- No.-

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.

Bisphenol A exposure through receipt handling and its association with insulin resistance among female cashiers

Lee, Inae,Kim, Sunmi,Kim, Ki-Tae,Kim, Sungkyoon,Park, Suhyun,Lee, Hyojin,Jeong, Yunsun,Lim, Jae-Eun,Moon, Hyo-Bang,Choi, Kyungho Elsevier 2018 Environment international Vol.117 No.-

<P><B>Abstract</B></P> <P>Bisphenol A (BPA) is one of the most widely used chemicals in various consumer products. In thermal papers such as receipts and tickets, BPA is used as a heat-activated developer. Cashiers are therefore suspected to be a vulnerable group of exposure to BPA, but neither contribution of receipt handling to the total body burden of BPA among cashiers, nor related health effects are well characterized. Female cashiers (n = 54) were recruited from seven retail shops of a major supermarket chain in Korea, and urinary levels of BPA and metabolic syndrome (MetS) related biomarkers were measured. In order to estimate the contribution of receipt handling to the body burden of BPA, an intervention was designed on the use of gloves: the subjects were asked not to wear gloves during the work for one week, and in the following week, to wear gloves. Urine samples were collected at pre-shift and post-shift for the first two consecutive days in each week, and urinary BPA concentrations were measured. In cashiers without gloves, about a two-fold increase in urinary BPA concentrations was observed after work-shift. When the cashiers wore gloves, however, urinary BPA levels showed no changes. Higher urinary BPA concentrations were associated with greater levels of fasting insulin and insulin resistance. Our observation shows that receipt handling among the cashiers could double the BPA exposure levels at post-shift compared to those at pre-shift, and use of simple protective equipment such as gloves could effectively reduce the BPA exposure levels.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Contribution of receipt handling to body burden of BPA was determined in cashiers. </LI> <LI> Without gloves, urinary BPA levels increased by two folds following work-shift. </LI> <LI> Use of gloves could efficiently prevent occupational exposure to BPA. </LI> <LI> Urinary BPA levels were associated with increased insulin levels and resistance. </LI> </UL> </P>