Publications by authors named "Ji Hoon Jeong"

327 Publications

Heparin-Mimicking Polymer-Based In Vitro Platform Recapitulates In Vivo Muscle Atrophy Phenotypes.

Int J Mol Sci 2021 Mar 2;22(5). Epub 2021 Mar 2.

Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea.

The cell-cell/cell-matrix interactions between myoblasts and their extracellular microenvironment have been shown to play a crucial role in the regulation of in vitro myogenic differentiation and in vivo skeletal muscle regeneration. In this study, by harnessing the heparin-mimicking polymer, poly(sodium-4-styrenesulfonate) (PSS), which has a negatively charged surface, we engineered an in vitro cell culture platform for the purpose of recapitulating in vivo muscle atrophy-like phenotypes. Our initial findings showed that heparin-mimicking moieties inhibited the fusion of mononucleated myoblasts into multinucleated myotubes, as indicated by the decreased gene and protein expression levels of myogenic factors, myotube fusion-related markers, and focal adhesion kinase (FAK). We further elucidated the underlying molecular mechanism via transcriptome analyses, observing that the insulin/PI3K/mTOR and Wnt signaling pathways were significantly downregulated by heparin-mimicking moieties through the inhibition of FAK/Cav3. Taken together, the easy-to-adapt heparin-mimicking polymer-based in vitro cell culture platform could be an attractive platform for potential applications in drug screening, providing clear readouts of changes in insulin/PI3K/mTOR and Wnt signaling pathways.
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http://dx.doi.org/10.3390/ijms22052488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957884PMC
March 2021

Hyaluronic Acid Coating on Hydrophobic Tracheal Scaffold Enhances Mesenchymal Stem Cell Adhesion and Tracheal Regeneration.

Tissue Eng Regen Med 2021 Apr 25;18(2):225-233. Epub 2021 Mar 25.

Department of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu Seoul, 03080, Republic of Korea.

Background: Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model.

Methods: A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups.

Results: HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group.

Conclusion: HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.
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http://dx.doi.org/10.1007/s13770-021-00335-2DOI Listing
April 2021

Capmatinib attenuates lipogenesis in 3T3-L1 adipocytes through an adenosine monophosphate-activated protein kinase-dependent pathway.

Biochem Biophys Res Commun 2021 Mar 20;553:30-36. Epub 2021 Mar 20.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Recently, there is a rapid increase in the incidence of obesity, a condition for which there are no effective therapeutic agents. Capmatinib (CAP), a novel mesenchymal-to-epithelial transition inhibitor, is reported to attenuate pro-inflammatory mediators and oxidative stress. In this study, the effects of CAP on lipogenesis in the adipocytes were examined. Treatment with CAP dose-dependently suppressed lipid accumulation in, and differentiation of, and increased lipolysis in, 3T3-L1 adipocytes. Additionally, CAP treatment augmented adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression in the adipocytes. Transfection with si-AMPK or si-FNDC5 mitigated the CAP-induced suppression of lipogenesis and enhanced lipolysis. Furthermore, transfection with si-FNDC5 mitigated the CAP-induced phosphorylation of AMPK. These results suggest that the anti-obesity effect of CAP is mediated through the irisin/AMPK pathway and that CAP is a novel therapeutic agent for obesity.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.064DOI Listing
March 2021

Development of an analytical method for multi-residue quantification of 18 anthelmintics in various animal-based food products using liquid chromatography-tandem mass spectrometry.

J Pharm Anal 2021 Feb 21;11(1):68-76. Epub 2020 Mar 21.

Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, Seoul, 143-701, Republic of Korea.

In this study, we developed a simple screening procedure for the determination of 18 anthelmintics (including benzimidazoles, macrocyclic lactones, salicylanilides, substituted phenols, tetrahydropyrimidines, and imidazothiazoles) in five animal-derived food matrices (chicken muscle, pork, beef, milk, and egg) using liquid chromatography-tandem mass spectrometry. Analytes were extracted using acetonitrile/1% acetic acid (milk and egg) and acetonitrile/1% acetic acid with 0.5 mL of distilled water (chicken muscle, pork, and beef), and purified using saturated -hexane/acetonitrile. A reversed-phase analytical column and a mobile phase consisting of (A) 10 mM ammonium formate in distilled water and (B) methanol were used to achieve optimal chromatographic separation. Matrix-matched standard calibration curves ( ≥0.9752) were obtained for concentration equivalent to ×1/2, ×1, ×2, ×3, ×4, and ×5 fold the maximum residue limit (MRL) stipulated by the Korean Ministry of Food and Drug Safety. Recoveries of 61.2-118.4%, with relative standard deviations (RSDs) of ≤19.9% (intraday and interday), were obtained for each sample at three spiking concentrations (×1/2, ×1, and ×2 the MRL values). Limits of detection, limits of quantification, and matrix effects were 0.02-5.5 μg/kg, 0.06-10 μg/kg, and -98.8 to 13.9% (at 20 μg/kg), respectively. In five samples of each food matrix (chicken muscle, pork, beef, milk, and egg) purchased from large retailers in Seoul that were tested, none of the target analytes were detected. It has therefore been shown that this protocol is adaptable, accurate, and precise for the quantification of anthelmintic residues in foods of animal origin.
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http://dx.doi.org/10.1016/j.jpha.2020.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930640PMC
February 2021

Meteorin-like protein (METRNL)/IL-41 improves LPS-induced inflammatory responses via AMPK or PPARδ-mediated signaling pathways.

Adv Med Sci 2021 Feb 13;66(1):155-161. Epub 2021 Feb 13.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Purpose: Meteorin-like protein (METRNL) (also known as IL-41), recently identified as a myokine, is released in response to muscle contraction. It improves the skeletal muscle insulin sensitivity through exerting a beneficial anti-inflammatory effect. However, no independent studies have been published to verify the effects of METRNL on human umbilical vein endothelial cells (HUVECs) and THP-1 human monocytes.

Materials And Methods: The levels of NFκB and IκB phosphorylation as well as the expression of adhesion molecules were assessed by Western blotting analysis. Cell adhesion assay demonstrated the interactions between HUVEC and THP-1 ​cells. We used enzyme-linked immunosorbent assay (ELISA) to measure the levels of TNFα and MCP-1 in culture medium.

Results: Treatment with METRNL suppressed the secretion of TNFα and MCP-1 as well as NFκB and IκB phosphorylation and inflammatory markers in lipopolysaccharide (LPS)-treated HUVECs and THP-1 ​cells. Furthermore, treatment with METRNL ameliorated LPS-induced attachment of THP-1 monocytes to HUVECs via inhibition of adhesion molecule expression and apoptosis. Treatment of HUVEC and THP-1 ​cells with METRNL enhanced AMPK phosphorylation and PPARδ expression in a dose-dependent manner. Small interference (si) RNA-mediated suppression of AMPK or PPARδ restored all these changes.

Conclusions: It has therefore been shown that METRNL ameliorates inflammatory responses through AMPK and PPARδ-dependent pathways in LPS-treated HUVEC. In sum, the current study may suggest the suppressive potential of METRNL against endothelial inflammation.
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http://dx.doi.org/10.1016/j.advms.2021.01.007DOI Listing
February 2021

Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters.

MAbs 2021 Jan-Dec;13(1):1868078

Department of Gastroenterology, Nancy University Hospital , Vandoeuvre-Les-Nancy, France.

The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as "biobetters" or "value-added medicines," are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.
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http://dx.doi.org/10.1080/19420862.2020.1868078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889098PMC
February 2021

Development of a Human-Display Interface with Vibrotactile Feedback for Real-World Assistive Applications.

Sensors (Basel) 2021 Jan 15;21(2). Epub 2021 Jan 15.

Department of Brain and Cognitive Engineering, Korea University, Seoul 02841, Korea.

It is important to operate devices with control panels and touch screens assisted by haptic feedback in mobile environments such as driving automobiles and electric power wheelchairs. A lot of consideration is needed to give accurate haptic feedback, especially, presenting clear touch feedback to the elderly and people with reduced sensation is a very critical issue from healthcare and safety perspectives. In this study, we aimed to identify the perceptual characteristics for the frequency and direction of haptic vibration on the touch screen with vehicle-driving vibration and to propose an efficient haptic system based on these characteristics. As a result, we demonstrated that the detection threshold shift decreased at frequencies above 210 Hz due to the contact pressure during active touch, but the detection threshold shift increased at below 210 Hz. We found that the detection thresholds were 0.30-0.45 gpeak with similar sensitivity in the 80-270 Hz range. The haptic system implemented by reflecting the experimental results achieved characteristics suitable for use scenarios in automobiles. Ultimately, it could provide practical guidelines for the development of touch screens to give accurate touch feedback in the real-world environment.
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http://dx.doi.org/10.3390/s21020592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830928PMC
January 2021

Glutathione peroxidase-1 and neuromodulation: Novel potentials of an old enzyme.

Food Chem Toxicol 2021 Feb 29;148:111945. Epub 2020 Dec 29.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

Glutathione peroxidase (GPx) acts in co-ordination with other signaling molecules to exert its own antioxidant role. We have demonstrated the protective effects of GPx,/GPx-1, a selenium-dependent enzyme, on various neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, cerebral ischemia, and convulsive disorders). In addition, we summarized the recent findings indicating that GPx-1 might play a role as a neuromodulator in neuropsychiatric conditions, such as, stress, bipolar disorder, schizophrenia, and drug intoxication. In this review, we attempted to highlight the mechanistic scenarios mediated by the GPx/GPx-1 gene in impacting these neurodegenerative and neuropsychiatric disorders, and hope to provide new insights on the therapeutic interventions against these disorders.
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http://dx.doi.org/10.1016/j.fct.2020.111945DOI Listing
February 2021

Endogenous metabolite, kynurenic acid, attenuates nonalcoholic fatty liver disease via AMPK/autophagy- and AMPK/ORP150-mediated signaling.

J Cell Physiol 2021 Jul 7;236(7):4902-4912. Epub 2020 Dec 7.

Department of Pharmacology, Chung-Ang University, Seoul, Republic of Korea.

Endoplasmic reticulum (ER) stress plays a causative role in the development of nonalcoholic fatty liver disease (NAFLD). Kynurenic acid (KA) is a tryptophan metabolite that has been shown to exert anti-inflammatory effects in macrophages and endothelial cells. However, the role of KA in ER stress-associated development of NAFLD has not been fully explored. In the current study, we observed decreased KA levels in the serum of obese subjects. Treated hepatocytes with KA attenuated palmitate-induced lipid accumulation and downregulated lipogenesis-associated genes as well as ER stress markers in a dose-dependent manner. Furthermore, KA augmented AMP-activated protein kinase (AMPK) phosphorylation, oxygen-regulated protein 150 (ORP150) expression, and autophagy markers. The small interfering RNA-mediated suppression of AMPK and ORP150, or 3-methyladenine also abrogated the effects of KA on ER stress and lipid accumulation in hepatocytes. In accordance with in vitro observations, KA administration to mice fed a high-fat diet ameliorated hepatic lipid accumulation and decreased the expression of lipogenic genes as well as ER stress. Moreover, KA treatment increased hepatic AMPK phosphorylation, ORP150 expression, and autophagy related markers in mouse livers. Knockdown of AMPK using in vivo transfection mitigated the effects of KA on hepatic steatosis and ER stress as well as autophagy and ORP150 expression. These results suggest that KA ameliorates hepatic steatosis via the AMPK/autophagy- and AMPK/ORP150-mediated suppression of ER stress. In sum, KA might be used as a promising therapeutic agent for treatment of NAFLD.
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http://dx.doi.org/10.1002/jcp.30199DOI Listing
July 2021

An adenoviral vector encoded with the GPx-1 gene attenuates memory impairments induced by β-amyloid (1-42) in GPx-1 KO mice via activation of M1 mAChR-mediated signalling.

Free Radic Res 2020 Dec 10:1-15. Epub 2020 Dec 10.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea.

In the present study, we examined whether glutathione peroxidase-1 (GPx-1), a major HO scavenger in the brain, affects memory deficits induced by Aβ (1-42) in mice. Treatment with 400 pmol/5 μl Aβ (1-42) (i.c.v.) resulted in a reduction of GPx-1 expression in wild-type (WT) mice. An Aβ (1-42)-induced reduction in acetylcholine (ACh) level was observed in the hippocampus. Treatment with Aβ (1-42) consistently resulted in reduced expression and activity of choline acetyltransferase (ChAT) and in an increase in expression and activity of acetylcholinesterase (AChE). Upon examining each of the muscarinic acetylcholine receptors (mAChRs) and nicotinic AChRs, we noted that Aβ (1-42) treatment selectively reduced the levels of M1 mAChR. In addition, Aβ (1-42) induced a significant reduction in phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) expression. The cholinergic impairments induced by Aβ (1-42) were more pronounced in GPx-1 knockout mice than in WT mice. Importantly, an adenoviral vector encoded with the GPx-1 gene (Ad-GPx-1) significantly rescued Aβ (1-42)-induced cholinergic impairments in GPx-1 knockout mice. In addition, M1 mAChR antagonist dicyclomine significantly counteracted Ad-GPx-1-mediated increases in p-CREB and BDNF expression, as well as memory-enhancing effects in GPx-1 knockout mice, thus indicating that M1 mAChR might be a critical mediator for the rescue effects of Ad-GPx-1. Combined, our results suggest that GPx-1 gene protected against Aβ (1-42)-induced memory impairments activation of M1 mAChR-dependent CREB/BDNF signalling.
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http://dx.doi.org/10.1080/10715762.2020.1854455DOI Listing
December 2020

Glutathione Peroxidase-1 Knockout Facilitates Memory Impairment Induced by β-Amyloid (1-42) in Mice via Inhibition of PKC βII-Mediated ERK Signaling; Application with Glutathione Peroxidase-1 Gene-Encoded Adenovirus Vector.

Neurochem Res 2020 Dec 16;45(12):2991-3002. Epub 2020 Oct 16.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.

A growing body evidence suggests that selenium (Se) deficiency is associated with an increased risk of developing Alzheimer's disease (AD). Se-dependent glutathione peroxidase-1 (GPx-1) of a major antioxidant enzyme, and the most abundant isoform of GPx in the brain. In the present study, we investigated whether GPx-1 is protective against memory impairments induced by beta-amyloid (Aβ) (1-42) in mice. As the alteration of protein kinase C (PKC)-mediated ERK activation was recognized in the early stage of AD, we examined whether the GPx-1 gene modulates Aβ (1-42)-induced changes in PKC and ERK levels. We observed that Aβ (1-42) treatment (400 pmol, i.c.v.) significantly decreased PKC βII expression in the hippocampus of mice. Aβ (1-42)-induced neurotoxic changes [i.e., oxidative stress (i.e., reactive oxygen species, 4-hydroxy-2-noneal, and protein carbonyl), reduced PKC βII and phospho-ERK expressions, and memory impairment under Y-maze and passive avoidance test] were more pronounced in GPx-1 knockout than in wild type mice. Importantly, exposure to a GPx-1 gene-encoded adenovirus vector (Adv-GPx-1) significantly increased GPx-1 mRNA and GPx activity in the hippocampus of GPx-1 knockout mice. Adv-GPx-1 exposure also significantly blocked the neurotoxic changes induced by Aβ (1-42) in GPx-1 knockout mice. Treatment with ERK inhibitor U0126 did not significantly change Adv-GPx-1-mediated attenuation in PKC βII expression. In contrast, treatment with PKC inhibitor chelerythrine (CHE) reversed Adv-GPx-1-mediated attenuation in ERK phosphorylation, suggesting that PKC βII-mediated ERK signaling is important for Adv-GPx-1-mediated potentials against Aβ (1-42) insult. Our results suggest that treatment with the antioxidant gene GPx-1 rescues Aβ (1-42)-induced memory impairment via activating PKC βII-mediated ERK signaling.
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http://dx.doi.org/10.1007/s11064-020-03147-3DOI Listing
December 2020

Multimodal signal dataset for 11 intuitive movement tasks from single upper extremity during multiple recording sessions.

Gigascience 2020 10;9(10)

Department of Brain and Cognitive Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, South Korea.

Background: Non-invasive brain-computer interfaces (BCIs) have been developed for realizing natural bi-directional interaction between users and external robotic systems. However, the communication between users and BCI systems through artificial matching is a critical issue. Recently, BCIs have been developed to adopt intuitive decoding, which is the key to solving several problems such as a small number of classes and manually matching BCI commands with device control. Unfortunately, the advances in this area have been slow owing to the lack of large and uniform datasets. This study provides a large intuitive dataset for 11 different upper extremity movement tasks obtained during multiple recording sessions. The dataset includes 60-channel electroencephalography, 7-channel electromyography, and 4-channel electro-oculography of 25 healthy participants collected over 3-day sessions for a total of 82,500 trials across all the participants.

Findings: We validated our dataset via neurophysiological analysis. We observed clear sensorimotor de-/activation and spatial distribution related to real-movement and motor imagery, respectively. Furthermore, we demonstrated the consistency of the dataset by evaluating the classification performance of each session using a baseline machine learning method.

Conclusions: The dataset includes the data of multiple recording sessions, various classes within the single upper extremity, and multimodal signals. This work can be used to (i) compare the brain activities associated with real movement and imagination, (ii) improve the decoding performance, and (iii) analyze the differences among recording sessions. Hence, this study, as a Data Note, has focused on collecting data required for further advances in the BCI technology.
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http://dx.doi.org/10.1093/gigascience/giaa098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539536PMC
October 2020

Decoding of Grasp Motions from EEG Signals Based on a Novel Data Augmentation Strategy.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3015-3018

Electroencephalogram (EEG) based braincomputer interface (BCI) systems are useful tools for clinical purposes like neural prostheses. In this study, we collected EEG signals related to grasp motions. Five healthy subjects participated in this experiment. They executed and imagined five sustained-grasp actions. We proposed a novel data augmentation method that increases the amount of training data using labels obtained from electromyogram (EMG) signals analysis. For implementation, we recorded EEG and EMG simultaneously. The data augmentation over the original EEG data concluded higher classification accuracy than other competitors. As a result, we obtained the average classification accuracy of 52.49(±8.74)% for motor execution (ME) and 40.36(±3.39)% for motor imagery (MI). These are 9.30% and 6.19% higher, respectively than the result of the comparable methods. Moreover, the proposed method could minimize the need for the calibration session, which reduces the practicality of most BCIs. This result is encouraging, and the proposed method could potentially be used in future applications such as a BCI-driven robot control for handling various daily use objects.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175784DOI Listing
July 2020

Clinically confirmed DEL-1 as a myokine attenuates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes via AMPK/HO-1- pathway.

Adipocyte 2020 12;9(1):576-586

Department of Pharmacology, College of Medicine, Chung-Ang University , Seoul, Republic of Korea.

Regular exercise is the first line of therapy for treating obesity-mediated metabolic disorders, including insulin resistance. It has been reported that developmental endothelial locus-1 (DEL-1) enhances macrophage efferocytosis, resulting in inflammation clearance as well as improves insulin resistance in skeletal muscle. However, the relationship between exercise and DEL-1, and the effects of DEL-1 on insulin signalling in adipocytes have not been fully elucidated to date. Protein expression levels were determined by Western blot analysis. Cells were transfected with small interfering (si) RNA to suppress gene expression. Lipid accumulation levels were detected using Oil red-O staining. Proinflammatory cytokine secretion levels were measured using ELISA. DEL-1 expression levels were induced in the skeletal muscle of people who exercised using microarray analysis. Recombinant DEL-1 augmented AMP-activated protein kinase (AMPK) phosphorylation and haem oxygenase (HO)-1 expression to alleviating inflammation and impairment of insulin signalling in 3T3-L1 adipocytes treated with palmitate. siRNA of AMPK or HO-1 also mitigated the effects of DEL-1 on inflammation and insulin resistance. DEL-1 ameliorates inflammation and insulin resistance in differentiated 3T3-L1 cells via AMPK/HO-1 signalling, suggesting that DEL-1 may be the exercise-mediated therapeutic target for treating insulin resistance and type 2 diabetes.
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http://dx.doi.org/10.1080/21623945.2020.1823140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714434PMC
December 2020

1,2-Dilinoleoyl-sn-glycero-3-phosphocholine increases insulin sensitivity in palmitate-treated myotubes and induces lipolysis in adipocytes.

Biochem Biophys Res Commun 2020 11 14;533(1):162-167. Epub 2020 Sep 14.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drug, the Graduate School of Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Obesity causes the development of insulin resistance and type 2 diabetes. Phosphatidylcholine (PPC) has been reported to increase hepatic insulin sensitivity and lipolysis in adipose tissue to resolve local obesity. In this study, we proposed 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), the main active species of PPC, as an effective substance for the treatment of obesity-mediated disorders such as impaired fat metabolism and insulin resistance. Therefore, we investigated the potential lipolytic effects of DLPC on adipocytes and insulin signaling in muscle cells. In this study, DLPC-treated 3T3-L1 adipocytes showed enhanced tumor necrosis factor α (TNF-α) release. Suppression of TNF-α by short interfering RNA (siRNA) mitigated DLPC-induced lipolysis and apoptosis. DLPC treatment increased peroxisome proliferator-activated receptor α (PPARα) expression levels in C2C12 myocytes. siRNA-mediated suppression of PPARα abrogated the suppressive effects of DLPC on palmitate-induced inflammation and insulin resistance. In conclusion, DLPC enhanced lipolysis and apoptosis via a TNFα-dependent pathway in adipocytes and attenuated palmitate-induced insulin resistance through PPARα-mediated suppression of inflammation in myocytes.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.019DOI Listing
November 2020

Glutathione peroxidase-1 knockout potentiates behavioral sensitization induced by cocaine in mice via σ-1 receptor-mediated ERK signaling: A comparison with the case of glutathione peroxidase-1 overexpressing transgenic mice.

Brain Res Bull 2020 11 18;164:107-120. Epub 2020 Aug 18.

Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

We demonstrated that the gene of glutathione peroxidase-1 (GPx-1), a major antioxidant enzyme, is a potential protectant against the neurotoxicity and conditioned place preference induced by cocaine. Because the sigma (σ)-1 receptor is implicated in cocaine-induced drug dependence, we investigated whether the GPx-1 gene modulates the σ-1 receptor in the behavioral sensitization induced by cocaine. Cocaine-induced behavioral sensitization was more pronounced in GPx-1 knockout (KO) than wild-type (WT) mice and was less pronounced in GPx-1 overexpressing transgenic (GPx-1 TG) than non-TG mice. Cocaine treatment significantly enhanced the oxidative burden and reduced the GSH levels in the striatum of WT, GPx-1 KO, and non-TG mice but not in that of GPx-1 TG mice. In addition, cocaine significantly increased the nuclear translocation, its DNA binding activity of nuclear factor erythroid-2-related factor 2 (Nrf2) as well as the mRNA expression of γ-glutamylcysteine (GCL). The genetic depletion of GPx-1 inhibited the Nrf2-related glutathione system, whereas the genetic overexpression of GPx-1 activated this system against behavioral sensitization. BD1047, a σ-1 receptor antagonist, and U0126, an ERK inhibitor significantly induced the Nrf2-related antioxidant potential against behavioral sensitization. Unlike BD1047, U0126 did not affect the cocaine-induced σ-1 receptor immunoreactivity, suggesting that the σ-1 receptor is an upstream molecule for ERK signaling. Importantly, BD1047 and U0126 failed to affect the σ-1 receptor immunoreactivity and ERK phosphorylation induced by cocaine in GPx-1 TG mice. Our results suggest that GPx-1 is a critical mediator for the attenuation of cocaine-induced behavioral sensitization via modulating σ-1 receptor-mediated ERK activation by the induction of the Nrf2-related system.
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http://dx.doi.org/10.1016/j.brainresbull.2020.08.011DOI Listing
November 2020

Enhanced Cancer DNA Vaccine Direct Transfection to Host Dendritic Cells Recruited in Injectable Scaffolds.

ACS Nano 2020 09 24;14(9):11623-11636. Epub 2020 Aug 24.

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.

Deoxyribonucleic acid (DNA) vaccines are a promising cancer immunotherapy approach. However, effective delivery of DNA to antigen-presenting cells (.., dendritic cells (DCs)) for the induction of an adaptive immune response is limited. Conventional DNA delivery intramuscular, intradermal, and subcutaneous injection by hypodermal needles shows a low potency and immunogenicity. Here, we propose the enhanced cancer DNA vaccine by direct transfection to the high number of DCs recruited into the chemoattractant-loaded injectable mesoporous silica microrods (MSRs). Subcutaneous administration of the MSRs mixed with tumor-antigen coding DNA polyplexes resulted in DC recruitment in the macroporous space of the scaffold formed by the spontaneous assembly of high-aspect-ratio MSRs, thereby allowing for enhanced cellular uptake of antigen-coded DNA by host DCs. The MSR scaffolds delivering the DNA vaccine trigger a more robust DC activation, antigen-specific CD8 T cell response, and Th1 immune response compared to the bolus DNA vaccine. Additionally, the immunological memory can be induced with a single administration of the vaccine. The combination of the vaccination and antiprogrammed cell death-1 antibody significantly eliminates established lung metastasis. These results indicate that MSRs serve as a powerful platform for DNA vaccine delivery to DCs for effective cancer immunotherapy.
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http://dx.doi.org/10.1021/acsnano.0c04188DOI Listing
September 2020

The Suppressive Effect of Leucine-Rich Glioma Inactivated 3 (LGI3) Peptide on Impaired Skin Barrier Function in a Murine Model Atopic Dermatitis.

Pharmaceutics 2020 Aug 10;12(8). Epub 2020 Aug 10.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 06974, Korea.

This study aimed to restore the skin barrier function from atopic dermatitis (AD) via treatment with leucine-rich glioma inactivated 3 (LGI3) peptide. Male NC/Nga mice (7 weeks, 20 g) were randomly allocated into three groups (control, AD, and LGI3 group). After induction of AD skin lesions with ointment, mice were treated with LGI3. The clinical score of AD was the highest and the dorsal skin thickness was the thickest in the AD group. In contrast, LGI3 treatment improved the clinical score and the dorsal skin thickness compared to the AD model. LGI3 treatment suppressed histopathological thickness of the epithelial cell layer of the dorsal skin. LGI3 treatment could indirectly reduce mast cell infiltration through restoring the barrier function of the skin. Additionally, the filaggrin expression was increased in immunohistochemical evaluation. In conclusion, the ameliorating effect and maintaining skin barrier homeostasis in the AD murine model treated with LGI3 could be attributed to complete re-epithelialization of keratinocytes. Hence, LGI3 might be considered as a new potential therapeutic target for restoring skin barrier function in AD.
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http://dx.doi.org/10.3390/pharmaceutics12080750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463480PMC
August 2020

Administration of kynurenic acid reduces hyperlipidemia-induced inflammation and insulin resistance in skeletal muscle and adipocytes.

Mol Cell Endocrinol 2020 12 21;518:110928. Epub 2020 Jul 21.

Department of Pharmacology, College of Medicine, Chung-Ang University, 221, Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Republic of Korea. Electronic address:

Kynurenic acid (KA), an endogenous product of L-tryptophan metabolism in the kynurenine pathway, regulates adipose tissue energy homeostasis and inflammation. However, its role in palmitate-induced insulin resistance and detailed underlying mechanisms in skeletal muscles and adipose tissues are unclear. Herein, we report that KA ameliorated palmitate-induced inflammation and insulin resistance in differentiated C2C12 and 3T3-L1 cell lines as well as soleus skeletal muscle and subcutaneous adipose tissues in mice. Palmitate-induced inflammatory markers, such as nuclear factor κB translocation, inhibitory κBα phosphorylation, pro-inflammatory cytokine expression, and impaired insulin signaling, were markedly attenuated by KA both in vitro and in vivo. KA significantly increased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 6 (SIRT6) expressions in C2C12 myocytes and 3T3-L1 adipocytes and skeletal muscle and adipose tissues of mice. siRNA-mediated AMPK or SIRT6 inhibition significantly mitigated the suppressive effects of KA on palmitate-induced inflammation and insulin resistance. KA significantly stimulated expression of genes involved in fatty acid oxidation in C2C12 myocytes and skeletal muscle of mice. Moreover, KA inhibits lipogenesis in 3T3-L1 adipocytes. AMPK or SIRT6 siRNA markedly reversed these changes. The siRNA targeting Gpr35 abrogated the effects of KA on AMPK phosphorylation in C2C12 myocytes and 3T3-L1 adipocytes, except SIRT6 expression. It has therefore been shown that KA could potentially alleviate inflammation and insulin resistance in skeletal muscle and adipose tissues through Gpr35/AMPK and SIRT6-mediated pathways.
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http://dx.doi.org/10.1016/j.mce.2020.110928DOI Listing
December 2020

A New TGF-β1 Inhibitor, CTI-82, Antagonizes Epithelial-Mesenchymal Transition through Inhibition of Phospho-SMAD2/3 and Phospho-ERK.

Biology (Basel) 2020 Jun 28;9(7). Epub 2020 Jun 28.

Department of Biomedical Sciences, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea.

Transforming growth factor-β1 (TGF-β1) is highly expressed in the tumor microenvironment and known to play a multifunctional role in cancer progression. In addition, TGF-β1 promotes metastasis by inducing epithelial-mesenchymal transition (EMT) in a variety of tumors. Thus, inhibition of TGF-β1 is considered an important strategy in the treatment of cancer. In most tumors, TGF-β1 signal transduction exhibits modified or non-functional characteristics, and TGF-β1 inhibitors have various inhibitory effects on cancer cells. Currently, many studies are being conducted to develop TGF-β1 inhibitors from non-toxic natural compounds. We aimed to develop a new TGF-β1 inhibitor to suppress EMT in cancer cells. As a result, improved chalcone-like chain CTI-82 was identified, and its effect was confirmed in vitro. We showed that CTI-82 blocked TGF-β1-induced EMT by inhibiting the cell migration and metastasis of A549 lung cancer cells. In addition, CTI-82 reduced the TGF-β1-induced phosphorylation of SMAD2/3 and inhibited the expression of various EMT markers. Our results suggest that CTI-82 inhibits tumor growth, migration, and metastasis.
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http://dx.doi.org/10.3390/biology9070143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408591PMC
June 2020

HDAC3-ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway.

Cells 2020 05 21;9(5). Epub 2020 May 21.

Department of Biomedical Sciences, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Korea.

Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3-ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3-ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3-ERα complex and substitution of the occupancy on the promoter by the p53-p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3-ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies.
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http://dx.doi.org/10.3390/cells9051280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290399PMC
May 2020

5-HT receptor-mediated PKCδ phosphorylation is critical for serotonergic impairments induced by p-chloroamphetamine in mice.

Food Chem Toxicol 2020 Jul 11;141:111395. Epub 2020 May 11.

Neuropsychopharmacology and Toxicology Program, BK21 PLUS Project, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea. Electronic address:

p-Chloroamphetamine (PCA), an amphetamine derivative, has been shown to induce serotonergic toxicity. However, the precise mechanism of serotonergic toxicity induced by PCA remains unclear. In this study, PCA treatment (20 mg/kg, i.p.) did not significantly change 5-HT receptor gene expression, but significantly increased 5-HT receptor gene expression. Furthermore, 5-HT receptor antagonist MDL11939, but not 5-HT receptor antagonist WAY100635, significantly attenuated PCA-induced serotonergic impairments. We investigated whether PCA activated a specific isoform of protein kinase C (PKC), since previous evidence indicated the involvement of PKC in neurotoxicity induced by amphetamines. We observed that PCA treatment significantly increased the expression levels of PKCδ among all PKC isoforms. MDL11939 treatment significantly attenuated PCA-induced phosphorylation of PKCδ. However, PCA-induced increase in 5-HT receptor gene expression was not altered by rottlerin (a pharmacological inhibitor of PKCδ) in mice, suggesting that 5-HT receptor is an upstream molecule for the activation of PKCδ. Rottlerin or PKCδ knockout significantly attenuated serotonergic behaviors. However, MDL11939 did not show any additional effects against the attenuation caused by PKCδ knockout in mice, suggesting that PKCδ gene is a molecular target for 5-HT receptor-mediated serotonergic effects. Our results suggest that 5-HT receptor mediates PCA-induced serotonergic impairments via activation of PKC.δ.
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http://dx.doi.org/10.1016/j.fct.2020.111395DOI Listing
July 2020

Ginsenoside Rb2 Ameliorates LPS-Induced Inflammation and ER Stress in HUVECs and THP-1 Cells via the AMPK-Mediated Pathway.

Am J Chin Med 2020 20;48(4):967-985. Epub 2020 May 20.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

Inflammation and endoplasmic reticulum (ER) stress have been documented to contribute to the development of atherosclerosis. Ginsenoside Rb2 has been reported to exhibit antidiabetic effects. However, the effects of Rb2 on atherosclerotic responses such as inflammation and ER stress in endothelial cells and monocytes remain unclear. In this study, the expression of inflammation and ER stress markers was determined using a Western blotting method. Concentrations of tumor necrosis factor alpha (TNF[Formula: see text]) and monocyte chemoattractant protein-1 (MCP-1) in culture media were assessed by enzyme-linked immunosorbent assay (ELISA) and apoptosis was evaluated by a cell viability assay and a caspase-3 activity measurement kit. We found that exposure of HUVECs and THP-1 monocytes to Rb2 attenuated inflammation and ER stress, resulting in amelioration of apoptosis and THP-1 cell adhesion to HUVECs under lipopolysaccharide (LPS) condition. Increased AMPK phosphorylation and heme oxygenase (HO)-1 expression, including GPR120 expression were observed in Rb2-treated HUVECs and THP-1 monocytes. Downregulation of both, AMPK phosphorylation and HO-1expression rescued these observed changes. Furthermore, GPR120 siRNA mitigated Rb2-induced AMPK phosphorylation. These results suggest that Rb2 inhibits LPS-mediated apoptosis and THP-1 cell adhesion to HUVECs by GPR120/AMPK/HO-1-associated attenuating inflammation and ER stress. Therefore, Rb2 can be used as a potential therapeutic molecule for treatment of atherosclerosis.
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http://dx.doi.org/10.1142/S0192415X20500469DOI Listing
September 2020

Messenger RNA/polymeric carrier nanoparticles for delivery of heme oxygenase-1 gene in the post-ischemic brain.

Biomater Sci 2020 Jun 29;8(11):3063-3071. Epub 2020 Apr 29.

Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 04763, Korea.

Ischemic stroke is a cerebrovascular disease caused by narrowed cerebral arteries. Thrombolytic agents such as tissue-plasminogen activators have been used for recanalization of the blood supply into the ischemic region. However, ischemia-reperfusion damage continues to increase the infarction volume. In this study, heme oxygenase-1 (HO1)-mRNA was delivered into the brain, using a non-viral carrier. Various non-viral carriers such as polyethylenimine (25 kDa, PEI25k), lipofectamine, dexamethasone-conjugated PEI2k (Dexa-PEI2k), deoxycholic acid-conjugated PEI2k (DA-PEI2k), and R3V6 peptides were evaluated as carriers of mRNA into the brain. Gene delivery assays showed that DA-PEI2k and lipofectamine had a higher mRNA delivery efficiency than the other carriers in Neuro2A cells in vitro and a rat brain in vivo. Cytotoxicity assays showed that lipofectamine had higher toxicity than DA-PEI2k. Therefore, DA-PEI2k was used for delivery of HO1-mRNA. Unlike plasmid DNA (pDNA), mRNA is expressed in the cytosol without nuclear translocation. This suggests that mRNA may have higher gene expression than pDNA, since the nuclear location of pDNA is an inefficient step. Indeed, in in vitro transfection assays, HO1-mRNA/DA-PEI2k had higher gene expression than HO1-pDNA/DA-PEI2k without induction of a pro-inflammatory cytokine. The therapeutic effects of HO1-mRNA delivery using DA-PEI2k were evaluated in the middle cerebral artery occlusion animal model after local injection. HO1-mRNA delivery had higher gene expression than HO1-pDNA delivery 24 h after the local injection. In addition, HO1-mRNA delivery reduced the infarct size more efficiently than HO1-pDNA delivery. The results suggest that the delivery of mRNA using DA-PEI2k may be useful for gene therapy of ischemic stroke.
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http://dx.doi.org/10.1039/d0bm00076kDOI Listing
June 2020

Protective Potential of Ginkgo biloba Against an ADHD-like Condition.

Curr Mol Pharmacol 2021 ;14(2):200-209

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 24341, Korea.

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder commonly found in children, which is recognized by hyperactivity and aggressive behavior. It is known that the pathophysiology of ADHD is associated with neurobiological dysfunction. Although psychostimulants are recognized as the therapeutic drugs of choice for ADHD patients, the side effects might be of great concern. Ginkgo biloba is a promising herbal, complementary supplement that may modulate the neuronal system in an ADHD-like condition. The beneficial effect of Ginkgo biloba on ADHD-like symptoms may be related to the modulation of the system by novel molecular mechanisms. Ginkgo biloba is known to modulate dopamine, serotonin, and norepinephrine signaling. Flavonoid glycosides and terpene trilactones are the two major phytochemical components present in the Ginkgo biloba preparations, which can exhibit antioxidant and neuroprotective activities. The pharmacological mechanisms of the phytochemical components may also contribute to the neuroprotective activity of Ginkgo biloba. In this review, we have summarized recent findings on the potential of various Ginkgo biloba preparations to treat ADHD-like symptoms. In addition, we have discussed the pharmacological mechanisms mediated by Ginkgo biloba against an ADHD-like condition.
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http://dx.doi.org/10.2174/1874467213666200424152454DOI Listing
January 2021

Aspirin Improves Nonalcoholic Fatty Liver Disease and Atherosclerosis through Regulation of the PPAR-AMPK-PGC-1 Pathway in Dyslipidemic Conditions.

Biomed Res Int 2020 19;2020:7806860. Epub 2020 Mar 19.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.

This study is aimed at elucidating how aspirin could systemically and simultaneously normalize nonalcoholic fatty liver disease (NAFLD) and atherosclerosis through both and studies in hyperlipidemic conditions. We evaluated the effects and mechanism of aspirin on the levels of various biomarkers related to NAFLD, atherosclerosis, and oxidative phosphorylation in cells and animals of hyperlipidemic conditions. The protein levels of biomarkers (PPAR, AMPK, and PGC-1) involved in oxidative phosphorylation in both the vascular endothelial and liver cells were elevated by the aspirin in hyperlipidemic condition. Also in the stimulation pathway of oxidative phosphorylation by aspirin, PPAR was a superior regulator than AMPK and PGC-1 in HepG2 cells. In the vascular endothelial cells, the phosphorylated endothelial nitric oxide synthase level was increased by the treatment. The protein levels of biomarkers related to lipid synthesis were decreased by the treatment in the liver cells. In rabbits administered with cholesterol diet, the levels of triglyceride, HDL-cholesterol, and alanine amino transferase in serums were ameliorated by the aspirin treatment, the levels of ATP and TNF were increased or decreased, respectively, by the aspirin in liver and aorta tissues, and mannose receptor and C-C chemokine receptor type 2 levels were increased or decreased by the aspirin in spleen, respectively. The elevated levels of macrophage antigen, angiotensin II type1 receptor, and lipid accumulation were decreased in both the liver and aorta tissues in the aspirin-treated group. In conclusion, aspirin can systemically and simultaneously ameliorate NAFLD and atherosclerosis by inhibiting lipid biosynthesis and inflammation and by elevating catabolic metabolism through the activation of the PPAR-AMPK-PGC-1 pathway. Furthermore, aspirin may normalize atherosclerosis and NAFLD by modulating the mannose receptor and CCR2 in macrophages.
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http://dx.doi.org/10.1155/2020/7806860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106881PMC
December 2020

Humanin attenuates palmitate-induced hepatic lipid accumulation and insulin resistance via AMPK-mediated suppression of the mTOR pathway.

Biochem Biophys Res Commun 2020 May 31;526(2):539-545. Epub 2020 Mar 31.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains unclear. Humanin (HN), a cytoprotective polypeptide, reportedly exhibits neuroprotective effects via suppression of inflammation and improvement of insulin resistance in neurons. This study aim was to investigate effects of HN on lipid accumulation in the hepatocytes and insulin signaling, and explore the underlying mechanisms. Protein expression levels were analyzed by Western blotting. Hepatic lipid accumulation was confirmed by Oil red-O staining. We found that HN-treatment ameliorated palmitate-induced lipid accumulation, expression of lipogenesis-associated genes (processed SREBP1, FAS, and SCD1), cell death, and caspase 3 activity in hepatocytes in a dose-dependent manner. Additionally, HN attenuated palmitate-induced impairment of insulin signaling. HN enhanced AMPK phosphorylation, whereas it suppressed palmitate-induced phosphorylation of mTOR. AMPK knockdown by siRNA neutralized the effects of HN on palmitic acid-treated hepatocytes. Collectively, HN prevents palmitate-induced hepatic lipid accumulation, apoptosis, and insulin resistance via AMPK-mediated suppression of the mTOR/SREBP1 pathway, suggesting that it may serve as a potential therapeutic agent in NAFLD treatment.
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http://dx.doi.org/10.1016/j.bbrc.2020.03.128DOI Listing
May 2020

Development of microRNA-21 mimic nanocarriers for the treatment of cutaneous wounds.

Theranostics 2020 10;10(7):3240-3253. Epub 2020 Feb 10.

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.

: Of the regulatory microRNAs expressed in the wounded skin, microRNA-21 (miR21) plays a pivotal role in wound repair by stimulating re-epithelialization, an essential feature to facilitate healing and reduce scar formation. Despite their crucial roles in wound healing, synthetic exogenous microRNAs have limited applications owing to the lack of an appropriate delivery system. Herein, we designed an miR21 mimic nanocarrier system using facial amphipathic bile acid-conjugated polyethyleneimines (BA-PEI) for the intracellular and transdermal delivery of synthetic miR21 molecules to accelerate wound repair. : To design miR21 mimic nanocarriers, BA-conjugated PEIs prepared from three different types of BA at molar feed ratios of 1 and 3 were synthesized. The intracellular uptake efficiency of synthetic miR21 mimics was studied using confocal laser scanning microscopy and flow cytometry analysis. The optimized miR21/BA nanocarrier system was used to evaluate the wound healing effects induced by miR21 mimics in human HaCaT keratinocytes and a murine excisional acute wound model . : The cell uptake efficiency of miR21 complexed with BA-conjugated PEI was dramatically higher than that of miR21 complexed with PEI alone. Deoxycholic acid (DA)-modified PEI at a molar feed ratio of 3:1 (DA3-PEI) showed the highest transfection efficiency for miR21 without any increase in toxicity. After effective transdermal and intracellular delivery of miR21/DA3 nanocarriers, miR21 mimics promoted cell migration and proliferation through the post-transcriptional regulation of programmed cell death protein 4 (PDCD4) and matrix metalloproteinases. Thus, miR21 mimic nanocarriers improved both the rate and quality of wound healing, as evident from enhanced collagen synthesis and accelerated wound re-epithelialization. : Our miRNA nanocarrier systems developed using DA3-PEI conjugates may be potentially useful for the delivery of synthetic exogenous miRNAs in various fields.
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http://dx.doi.org/10.7150/thno.39870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053209PMC
February 2020

Brain-Controlled Robotic Arm System Based on Multi-Directional CNN-BiLSTM Network Using EEG Signals.

IEEE Trans Neural Syst Rehabil Eng 2020 05 18;28(5):1226-1238. Epub 2020 Mar 18.

Brain-machine interfaces (BMIs) can be used to decode brain activity into commands to control external devices. This paper presents the decoding of intuitive upper extremity imagery for multi-directional arm reaching tasks in three-dimensional (3D) environments. We designed and implemented an experimental environment in which electroencephalogram (EEG) signals can be acquired for movement execution and imagery. Fifteen subjects participated in our experiments. We proposed a multi-directional convolution neural network-bidirectional long short-term memory network (MDCBN)-based deep learning framework. The decoding performances for six directions in 3D space were measured by the correlation coefficient (CC) and the normalized root mean square error (NRMSE) between predicted and baseline velocity profiles. The grand-averaged CCs of multi-direction were 0.47 and 0.45 for the execution and imagery sessions, respectively, across all subjects. The NRMSE values were below 0.2 for both sessions. Furthermore, in this study, the proposed MDCBN was evaluated by two online experiments for real-time robotic arm control, and the grand-averaged success rates were approximately 0.60 (±0.14) and 0.43 (±0.09), respectively. Hence, we demonstrate the feasibility of intuitive robotic arm control based on EEG signals for real-world environments.
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http://dx.doi.org/10.1109/TNSRE.2020.2981659DOI Listing
May 2020