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Jeongmin Lee,Sangwook Lee,Wooram Jung,Guk Bae Kim,Taehun Kim,Jiwon Seong,장혜민,Young Noh,Na Kyung Lee,Boo Rak Lee,Jung-Il Lee,Soo Jin Choi,Wonil Oh,Namkug Kim,Seunghoon Lee,Duk L. Na 대한의학회 2022 Journal of Korean medical science Vol.37 No.31
Background: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. Methods: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. Results: We compared the planned vs. insertion trajectory of IBI to the hippocampus. With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. Conclusion: Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.
Beneficial effects of melatonin on stroke-induced muscle atrophy in focal cerebral ischemic rats
Seunghoon Lee,Jinhee Shin,Yunkyung Hong,Minkyung Lee,Koo Kim,Sang-Rae Lee,Kyu-Tae Chang,Yonggeun Hong 한국실험동물학회 2012 Laboratory Animal Research Vol.28 No.1
Muscle atrophy is the result of two opposing conditions that can be found in pathological or diseased muscles: an imbalance in protein synthesis and degradation mechanisms. Thus, we investigated whether exogenous melatonin could regulate muscle components in stroke-induced muscle atrophy in rats. Comparing muscle phenotypes, we found that long-term melatonin administration could influence muscle mass. Muscle atrophy-related genes, including muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1) were significantly down-regulated in melatonin-administered rats in the gastrocnemius. However, only MAFbx at the mRNA level was attenuated in the soleus of melatonin-administered rats. Insulin-like growth factor-1 receptor (IGF-1R) was significantly over-expressed in melatonin-administered rats in both the gastrocnemius and soleus muscles. Comparing myosin heavy chain (MHC) components, in the gastrocnemius, expression of both slow- and fast-type isoforms were significantly enhanced in melatoninadministered rats. These results suggest that long-term exogenous melatonin administration may have a prophylactic effect on muscle atrophy through the MuRF1/MAFbx signaling pathway, as well as a potential therapeutic effect on muscle atrophy through the IGF-1-mediated hypertrophic signaling pathway in a stroke animal model.
Lee, Youngjeon,Lee, Seunghoon,Lee, Sang-Rae,Park, Kanghui,Hong, Yunkyung,Lee, Minkyung,Park, Sookyoung,Jin, Yunho,Chang, Kyu-Tae,Hong, Yonggeun Molecular Diversity Preservation International (MD 2014 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.15 No.2
<P>Endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI). We have previously shown that melatonin (MT) plus exercise (Ex) had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups. These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.</P>
GzSNF1 Is Required for Normal Sexual and Asexual Development in the Ascomycete Gibberella zeae
Lee, Seung-Ho,Lee, Jungkwan,Lee, Seunghoon,Park, Eun-Hee,Kim, Ki-Woo,Kim, Myoung-Dong,Yun, Sung-Hwan,Lee, Yin-Won American Society for Microbiology 2009 EUKARYOTIC CELL Vol.8 No.1
<B>ABSTRACT</B><P>The sucrose nonfermenting 1 (<I>SNF1</I>) protein kinase of yeast plays a central role in the transcription of glucose-repressible genes in response to glucose starvation. In this study, we deleted an ortholog of <I>SNF1</I> from <I>Gibberella zeae</I> to characterize its functions by using a gene replacement strategy. The mycelial growth of deletion mutants (ΔGz<I>SNF1</I>) was reduced by 21 to 74% on diverse carbon sources. The virulence of ΔGz<I>SNF1</I> mutants on barley decreased, and the expression of genes encoding cell-wall-degrading enzymes was reduced. The most distinct phenotypic changes were in sexual and asexual development. ΔGz<I>SNF1</I> mutants produced 30% fewer perithecia, which matured more slowly, and asci that contained one to eight abnormally shaped ascospores. Mutants in which only the Gz<I>SNF1</I> catalytic domain was deleted had the same phenotype changes as the ΔGz<I>SNF1</I> strains, but the phenotype was less extreme in the mutants with the regulatory domain deleted. In outcrosses between the ΔGz<I>SNF1</I> mutants, each perithecium contained ∼70% of the abnormal ascospores, and ∼50% of the asci showed unexpected segregation patterns in a single locus tested. The asexual spores of the ΔGz<I>SNF1</I> mutants were shorter and had fewer septa than those of the wild-type strain. The germination and nucleation of both ascospores and conidia were delayed in ΔGz<I>SNF1</I> mutants in comparison with those of the wild-type strain. GzSNF1 expression and localization depended on the developmental stage of the fungus. These results suggest that Gz<I>SNF1</I> is critical for normal sexual and asexual development in addition to virulence and the utilization of alternative carbon sources.</P>
Functional Analyses of Two Acetyl Coenzyme A Synthetases in the Ascomycete Gibberella zeae
Lee, Seunghoon,Son, Hokyoung,Lee, Jungkwan,Min, Kyunghun,Choi, Gyung Ja,Kim, Jin-Cheol,Lee, Yin-Won American Society for Microbiology 2011 EUKARYOTIC CELL Vol.10 No.8
<B>ABSTRACT</B><P> Acetyl coenzyme A (acetyl-CoA) is a crucial metabolite for energy metabolism and biosynthetic pathways and is produced in various cellular compartments with spatial and temporal precision. Our previous study on ATP citrate lyase (ACL) in Gibberella zeae revealed that ACL-dependent acetyl-CoA production is important for histone acetylation, especially in sexual development, but is not involved in lipid synthesis. In this study, we deleted additional acetyl-CoA synthetic genes, the acetyl-CoA synthetases ( <I>ACS</I> genes <I>ACS1</I> and <I>ACS2</I> ), to identify alternative acetyl-CoA production mechanisms for ACL. The <I>ACS1</I> deletion resulted in a defect in sexual development that was mainly due to a reduction in 1-palmitoyl-2-oleoyl-3-linoleoyl-rac-glycerol production, which is required for perithecium development and maturation. Another ACS coding gene, <I>ACS2</I> , has accessorial functions for <I>ACS1</I> and has compensatory functions for <I>ACL</I> as a nuclear acetyl-CoA producer. This study showed that acetate is readily generated during the entire life cycle of G. zeae and has a pivotal role in fungal metabolism. Because ACSs are components of the pyruvate-acetaldehyde-acetate pathway, this fermentation process might have crucial roles in various physiological processes for filamentous fungi. </P>
Numerical modeling of wind turbine aerodynamic noise in the time domain
Lee, Seunghoon,Lee, Seungmin,Lee, Soogab Acoustical Society of America 2013 JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA - Vol.133 No.2
<P>Aerodynamic noise from a wind turbine is numerically modeled in the time domain. An analytic trailing edge noise model is used to determine the unsteady pressure on the blade surface. The far-field noise due to the unsteady pressure is calculated using the acoustic analogy theory. By using a strip theory approach, the two-dimensional noise model is applied to rotating wind turbine blades. The numerical results indicate that, although the operating and atmospheric conditions are identical, the acoustical characteristics of wind turbine noise can be quite different with respect to the distance and direction from the wind turbine.</P>
Lee, Seunghoon,Lee, Hyeonhoon,Cho, Yeeun,Kim, Jihye,Kang, Jung Won,Seo, Byung-Kwan,Baek, Yong-Hyeon,Lee, Jae-Dong Wolters Kluwer Health 2018 Medicine Vol.97 No.38
<P><B>Abstract</B></P><P><B>Background:</B></P><P>This study aims to evaluate the efficacy, safety, and appropriate dose of Hanslim, a Korean traditional herbal medicine, for obese patients, when compared to a placebo.</P><P><B>Methods/design:</B></P><P>This study is a randomized, double-blinded, multicenter, multidose, placebo-controlled, phase IIb clinical trial. A total of 165 obese patients with a body mass index (BMI) of more than 30 kg/m<SUP>2</SUP> or obese patients with a BMI of 27 to 29.9 kg/m<SUP>2</SUP> and one or more risk factors such as hypertension, diabetes, or hyperlipidemia will be enrolled. Participants will be randomly assigned to 1 of 3 groups (high-dose, low-dose, or placebo) with a 1:1:1 allocation ratio and will have 4 scheduled visits during the 12-week treatment period. The participants will be administered 2 tablets of Hanslim or placebo, 2 times per day. The difference in the proportion of participants who lost weight by more than 5% from their baseline at 12 weeks compared to the placebo group will be examined as the primary efficacy outcome. Secondary efficacy outcomes include differences in body weight, BMI, body-fat percentage, fat mass, skeletal-muscle mass, edema index, waist circumference, hip circumference, waist-hip ratio, serum lipid, blood glucose, C-reactive protein, and total score of Korean version of obesity-related quality of life after 12 weeks of treatment. Adverse events, laboratory test results, vital sings, and electrocardiography will be recorded to evaluate safety.</P><P><B>Discussion:</B></P><P>This is the first prospective clinical trial to explore the efficacy and safety of Hanslim for obese patients. If the results provide the appropriate dosage of Hanslim, this study would contribute to the confirmatory evidence for the use of Hanslim as a treatment for obesity needed to conduct a large-scale, phase III clinical trial. The results will be published in a peer-reviewed journal.</P><P>Trial registration: Clinical Research Information Service, ID: KCT0002193. Registered on January 6, 2017. https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7468</P>