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Article ; Online: Effective derivation of ventricular cardiomyocytes from hPSCs using ascorbic acid-containing maturation medium

Ji-eun Kim / Eun-Mi Kim / Hyang-Ae Lee / Ki-Suk Kim

Animal Cells and Systems, Vol 27, Iss 1, Pp 83-

2023 Volume 93

Abstract: ABSTRACTCardiomyocytes derived from human pluripotent stem cells (hPSCs) can be used in various applications including disease modeling, drug safety screening, and novel cell-based cardiac therapies. Here, we report an optimized selection and maturation ... ...

Abstract	ABSTRACTCardiomyocytes derived from human pluripotent stem cells (hPSCs) can be used in various applications including disease modeling, drug safety screening, and novel cell-based cardiac therapies. Here, we report an optimized selection and maturation method to induce maturation of cardiomyocytes into a specific subtype after differentiation driven by the regulation of Wnt signaling. The medium used to optimize selection and maturation was in a glucose starvation conditions, supplemented with either a nutrition complex or ascorbic acid. Following optimized selection and maturation, more cardiac Troponin T (cTnT)-positive cardiomyocytes were detected using albumin and ascorbic acid than B27. In addition, ascorbic acid enriched maturation of ventricular cardiomyocytes. We compared cardiomyocyte-specific gene expression patterns under different selection and maturation conditions by next-generation sequencing (NGS) analysis. Our optimized conditions will enable simple and efficient maturation and specification of the desired cardiomyocyte subtype, facilitating both biomedical research and clinical applications.
Keywords	Cardiomyocyte ; ascorbic acid ; albumin ; Wnt signaling ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Medicinal Plants Qua Glucagon-Like Peptide-1 Secretagogue via Intestinal Nutrient Sensors

Ki-Suk Kim / Hyeung-Jin Jang

Evidence-Based Complementary and Alternative Medicine, Vol

2015 Volume 2015

Abstract: Glucagon-like peptide-1 (GLP-1) participates in glucose homeostasis and feeding behavior. Because GLP-1 is rapidly inactivated by the enzymatic cleavage of dipeptidyl peptidase-4 (DPP4) long-acting GLP-1 analogues, for example, exenatide and DPP4 ... ...

Abstract	Glucagon-like peptide-1 (GLP-1) participates in glucose homeostasis and feeding behavior. Because GLP-1 is rapidly inactivated by the enzymatic cleavage of dipeptidyl peptidase-4 (DPP4) long-acting GLP-1 analogues, for example, exenatide and DPP4 inhibitors, for example, liraglutide, have been developed as therapeutics for type 2 diabetes mellitus (T2DM). However, the inefficient clinical performance and the incidence of side effects reported on the existing therapeutics for T2DM have led to the development of a novel therapeutic strategy to stimulate endogenous GLP-1 secretion from enteroendocrine L cells. Since the GLP-1 secretion of enteroendocrine L cells depends on the luminal nutrient constituents, the intestinal nutrient sensors involved in GLP-1 secretion have been investigated. In particular, nutrient sensors for tastants, cannabinoids, and bile acids are able to recognize the nonnutritional chemical compounds, which are abundant in medicinal plants. These GLP-1 secretagogues derived from medicinal plants are easy to find in our surroundings, and their effectiveness has been demonstrated through traditional remedies. The finding of GLP-1 secretagogues is directly linked to understanding of the role of intestinal nutrient sensors and their recognizable nutrients. Concurrently, this study demonstrates the possibility of developing novel therapeutics for metabolic disorders such as T2DM and obesity using nutrients that are readily accessible in our surroundings.
Keywords	Other systems of medicine ; RZ201-999
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Electrophysiological mechanisms of vandetanib-induced cardiotoxicity

Hyang-Ae Lee / Sung-Ae Hyun / Byungjin Byun / Jong-Hak Chae / Ki-Suk Kim

PLoS ONE, Vol 13, Iss 4, p e

Comparison of action potentials in rabbit Purkinje fibers and pluripotent stem cell-derived cardiomyocytes.

2018 Volume 0195577

Abstract: Vandetanib, a multi-kinase inhibitor used for the treatment of various cancers, has been reported to induce several adverse cardiac effects. However, the underlying mechanisms of vandetanib-induced cardiotoxicity are unclear. This study aimed to ... ...

Abstract	Vandetanib, a multi-kinase inhibitor used for the treatment of various cancers, has been reported to induce several adverse cardiac effects. However, the underlying mechanisms of vandetanib-induced cardiotoxicity are unclear. This study aimed to investigate the mechanism of vandetanib-induced cardiotoxicity using intracellular electrophysiological recordings on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), rabbit Purkinje fibers, and HEK293 cells transiently expressing human ether-a-go-go-related gene (hERG; the rapidly activating delayed rectifier K+ channel, IKr), KCNQ1/KCNE1 (the slowly activating delayed rectifier K+ current, IKs), KCNJ2 (the inwardly rectifying K+ current, IK1) or SCN5A (the inward Na+ current, INa). Purkinje fiber assays and ion channel studies showed that vandetanib at concentrations of 1 and 3 μM inhibited the hERG currents and prolonged the action potential duration. Alanine scanning and in silico hERG docking studies demonstrated that Y652 and F656 in the hERG S6 domain play critical roles in vandetanib binding. In hiPSC-CMs, vandetanib markedly reduced the maximum rate of depolarization during the AP upstroke. Ion channel studies revealed that hiPSC-CMs were more sensitive to inhibition of the INa by vandetanib than in a heterogeneously expressed HEK293 cell model, consistent with the changes in the AP parameters of hiPSC-CMs. The subclasses of Class I antiarrhythmic drugs inhibited INa currents in a dose-dependent manner in hiPSC-CMs and SCN5A-encoded HEK293 cells. The inhibitory potency of vandetanib for INa was much higher in hiPSC-CMs (IC50: 2.72 μM) than in HEK293 cells (IC50: 36.63 μM). These data suggest that AP and INa assays using hiPSC-CMs are useful electrophysiological models for prediction of drug-induced cardiotoxicity.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cyclin-Dependent Kinase Inhibitor BMI-1026 Induces Apoptosis by Downregulating Mcl-1 (L) and c-FLIP (L) and Inactivating p-Akt in Human Renal Carcinoma Cells

Dong Eun Kim / Jinho Lee / Jong Wook Park / Hyunsu Kang / Yu Ri Nam / Taeg Kyu Kwon / Ki-Suk Kim / Shin Kim

International Journal of Molecular Sciences, Vol 22, Iss 4268, p

2021 Volume 4268

Abstract: Previous studies have investigated the inhibitory effect of BMI-1026 on cyclin-dependent kinase 1 in vitro. However, the molecular mechanisms by which BMI-1026 treatment leads to cancer cell death remain unclear. This study was conducted to investigate ... ...

Abstract	Previous studies have investigated the inhibitory effect of BMI-1026 on cyclin-dependent kinase 1 in vitro. However, the molecular mechanisms by which BMI-1026 treatment leads to cancer cell death remain unclear. This study was conducted to investigate the anticancer mechanisms of BMI-1026 on human renal carcinoma Caki cells. BMI-1026 induced apoptosis in association with the cleavage of poly(ADP-ribose) polymerase and pro-caspase-3 and the release of apoptosis-inducing factor and cytochrome c from mitochondria in Caki cells. BMI-1026-induced apoptosis was inhibited by the pan-caspase inhibitor z-VAD-fmk. Furthermore, BMI-1026 downregulated Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP) at the transcriptional level and Mcl-1 (L) and cellular FADD-like IL-1β-converting enzyme inhibitory protein (c-FLIP (L)) at the post-transcriptional level. Interestingly, Mcl-1 (L) and c-FLIP (L), but not Bcl-2 or XIAP, played important roles in BMI-1026-induced Caki cell apoptosis. Although the constitutively active form of Akt did not attenuate BMI-1026-induced apoptosis, blockade of the PI3K/Akt pathway using a subcytotoxic concentration of the PI3K/Akt inhibitor LY294002 enhanced Caki cell apoptosis induced by BMI-1026. Electrophysiological safety was confirmed by determining the cardiotoxicity of BMI-1026 via left ventricular pressure analysis. These results suggest that BMI-1026 is a potent multitarget anticancer agent with electrophysiological safety and should be further investigated.
Keywords	BMI-1026 ; apoptosis ; Mcl-1 ; cellular FADD-like IL-1β-converting enzyme inhibitory protein ; p-Akt ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modulation of M1/M2 polarization by capsaicin contributes to the survival of dopaminergic neurons in the lipopolysaccharide-lesioned substantia nigra in vivo

Eugene Bok / Young Cheul Chung / Ki-Suk Kim / Hyung Hwan Baik / Won-Ho Shin / Byung Kwan Jin

Experimental and Molecular Medicine, Vol 50, Iss 7, Pp 1-

2018 Volume 14

Abstract: Parkinson’s disease: Preventing neuron death A drug that activates a neuron-protecting protein in the brain may help treat Parkinson’s disease (PD). Scientists believe neurons die during PD because of an over-activation of proinflammatory markers within ... ...

Abstract	Parkinson’s disease: Preventing neuron death A drug that activates a neuron-protecting protein in the brain may help treat Parkinson’s disease (PD). Scientists believe neurons die during PD because of an over-activation of proinflammatory markers within immune cell populations, such as the microglia and macrophage cells found in the central nervous system and the brain. Now, Byung Kwan Jin at Kyung Hee University in Seoul and Won-Ho Shin at the Korea Institute of Toxicology in Daejeon and co-workers have demonstrated that a proinflammatory state can be reversed in rat PD models by administering capsaicin, an analgesic drug. Capsaicin activates a receptor protein that is highly expressed in neurons, microglia and astrocytes, and may play a role in neuronal function and motor control. The protein activation reversed the inflammatory state of the immune cells, providing a more protective environment for neurons.
Keywords	Medicine ; R ; Biochemistry ; QD415-436
Subject code	612
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Template-Assisted Electrochemical Synthesis of CdSe Quantum Dots—Polypyrrole Composite Nanorods

Won-Seok Kang / Taegon Oh / Gwang-Hyeon Nam / Hyo-Sop Kim / Ki-Suk Kim / Sun-Hyun Park / Jae-Ho Kim / Jae-Hyeok Lee

Applied Sciences, Vol 10, Iss 5966, p

2020 Volume 5966

Abstract: Luminescent nanoparticles have reached a high level of maturity in materials and spectral tunability for optics and optoelectronics. However, the lack of facile methodology for heterojunction formation of the nanoparticles provides many challenges for ... ...

Abstract	Luminescent nanoparticles have reached a high level of maturity in materials and spectral tunability for optics and optoelectronics. However, the lack of facile methodology for heterojunction formation of the nanoparticles provides many challenges for scalability. In this paper we demonstrate a simple procedure to synthesize a nanoparticle-embedded polymer nanorod hybrid structure via a template-based electrochemical method using anodic aluminum oxide membranes. This method enables the formation of interactive nanostructures wherein the interface area between the two components is maximized. As a proof of concept, semiconducting CdSe nanoparticles were embedded in polypyrrole nanorods with dimensions that can be finely tuned. We observed enhanced photoluminescence of the hybrid structures compared with bare polypyrrole nanorods.
Keywords	nanorod ; nanoparticles ; electrodeposition ; heterojunction ; optoelectronics ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	620
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats

Simon S. Evers / Ki-Suk Kim / Nadejda Bozadjieva / Alfor G. Lewis / Diana Farris / Matthew J. Sorensen / Youngsoo Kim / Steven E. Whitesall / Robert T. Kennedy / Daniel E. Michele / Randy J. Seeley / Darleen A. Sandoval

Molecular Metabolism, Vol 32, Iss , Pp 148-

2020 Volume 159

Abstract: Objective: Post–bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) ... ...

Abstract	Objective: Post–bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication. Therefore, a model system to investigate the mechanism and treatment is required. Methods: We used CGM in a rat model of VSG and monitored the occurrence of glycemic variability and hypoglycemia in various meal conditions for 4 weeks after surgery. Another cohort of VSG rats with CGM was used to investigate whether the blockade of glucagon-like peptide-1 receptor (GLP-1R) signaling alleviates these symptoms. A mouse VSG model was used to investigate whether the impaired glucose counterregulatory system causes postprandial hypoglycemia. Results: Like in humans, rats have increased glycemic variability and hypoglycemia after VSG. Postprandial hypoglycemia was specifically detected after liquid versus solid meals. Further, the blockade of GLP-1R signaling raises the glucose nadir but does not affect glycemic variability. Conclusions: Rat bariatric surgery duplicates many features of human post–bariatric surgery hypoglycemia including postprandial hypoglycemia and glycemic variability, while blockade of GLP-1R signaling prevents hypoglycemia but not the variability. Keywords: Continuous glucose monitoring, Vertical sleeve gastrectomy, Post–bariatric surgery hypoglycemia, Glycemic variability, Exendin 9-39, Glucagon-like peptide-1 receptor
Keywords	Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Functional fusion proteins and prevention of electrode fouling for a sensitive electrochemical immunosensor

Kim, A-Ram / Tae Jung Park / Minseok S. Kim / In-Ho Kim / Ki-Suk Kim / Kwang Hoe Chung / Sungho Ko

Analytica chimica acta. 2017,

2017

Abstract: A highly sensitive electrochemical immunosensor was developed by preventing electrode fouling and using a novel fusion protein of silica binding polypeptides (SBP)-protein G (ProG) created by recombinant DNA technology as a functional crosslinker for ... ...

Abstract	A highly sensitive electrochemical immunosensor was developed by preventing electrode fouling and using a novel fusion protein of silica binding polypeptides (SBP)-protein G (ProG) created by recombinant DNA technology as a functional crosslinker for rapid and self-oriented immobilization of antibodies onto silica nanoparticles (SiNPs). Antibody immobilization onto the SiNPs by the SBP-ProG could rapidly be achieved without any chemical treatment. The immunosensor was fabricated through bonding of a partially gold-deposited cyclic olefin copolymer (COC) (top substrate) and gold patterned interdigitated array COC electrode (bottom substrate). To prevent electrode fouling, human immunoglobulin G (hIgG) was immobilized onto the ceiling inside the microchannel, instead of the bottom electrode. Alkaline phosphatase (AP)-labeled anti-hIgG was allowed to immunoreact with hIgG on the ceiling, followed by addition of an enzyme to generate an oxidative peak current. A three-fold increase in current was observed from the immunosensor without any electrode fouling compared with a control with the protein functionalized electrode. Also, the SiNPs facilely coated with AP-anti-hIgG via the SBP-ProG could increase the electrochemical signal up to 20% larger than that of the AP-anti-hIgG alone. Furthermore, this immunosensor was ultrasensitive with a detection limit of 0.68Â pg/mL of a biomarker associated with prostate cancer.
Keywords	alkaline phosphatase ; analytical chemistry ; antibodies ; biomarkers ; chemical treatment ; composite polymers ; electrochemistry ; electrodes ; fouling ; gold ; humans ; immunoglobulin G ; immunosensors ; nanoparticles ; olefin ; polypeptides ; prostatic neoplasms ; recombinant DNA ; silica
Language	English
Size	p. .
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2017.02.026
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice

Ki-Suk Kim / In-Seung Lee / Kang-Hoon Kim / Jiyoung Park / Yumi Kim / Jeong-Hee Choi / Jin-Sung Choi / Hyeung-Jin Jang

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 11

Abstract: Abstract Odorants are non-nutrients. However, they exist abundantly in foods, wines, and teas, and thus can be ingested along with the other nutrients during a meal. Here, we have focused on the chemical-recognition ability of these ORs and hypothesized ... ...

Abstract	Abstract Odorants are non-nutrients. However, they exist abundantly in foods, wines, and teas, and thus can be ingested along with the other nutrients during a meal. Here, we have focused on the chemical-recognition ability of these ORs and hypothesized that the odorants ingested during a meal may play a physiological role by activating the gut-expressed ORs. Using a human-derived enteroendocrine L cell line, we discovered the geraniol- and citronellal-mediated stimulation of glucagon-like peptide-1 (GLP-1) secretion and elucidated the corresponding cellular downstream signaling pathways. The geraniol-stimulated GLP-1 secretion event in the enteroendocrine cell line was mediated by the olfactory-type G protein, the activation of adenylyl cyclase, increased intracellular cAMP levels, and extracellular calcium influx. TaqMan qPCR demonstrated that two ORs corresponding to geraniol and citronellal were expressed in the human enteroendocrine cell line and in mouse intestinal specimen. In a type 2 diabetes mellitus mouse model (db/db), oral administration of geraniol improved glucose homeostasis by increasing plasma GLP-1 and insulin levels. This insulinotropic action of geraniol was GLP-1 receptor-mediated, and also was glucose-dependent. This study demonstrates that odor compounds can be recognized by gut-expressed ORs during meal ingestion and therefore, participate in the glucose homeostasis by inducing the secretion of gut-peptides.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of BMP-2 Delivery Mode on Osteogenic Differentiation of Stem Cells

Taekhee Jung / John Hwan Lee / Soonjung Park / Yong-Jin Kim / Joseph Seo / Hye-Eun Shim / Ki-Suk Kim / Hyon-Seok Jang / Hyung-Min Chung / Seong-Geun Oh / Sung-Hwan Moon / Sun-Woong Kang

Stem Cells International, Vol

2017 Volume 2017

Abstract: Differentiation of stem cells is an important strategy for regeneration of defective tissue in stem cell therapy. Bone morphogenetic protein-2 (BMP-2) is a well-known osteogenic differentiation factor that stimulates stem cell signaling pathways by ... ...

Abstract	Differentiation of stem cells is an important strategy for regeneration of defective tissue in stem cell therapy. Bone morphogenetic protein-2 (BMP-2) is a well-known osteogenic differentiation factor that stimulates stem cell signaling pathways by activating transmembrane type I and type II receptors. However, BMPs have a very short half-life and may rapidly lose their bioactivity. Thus, a BMP delivery system is required to take advantage of an osteoinductive effect for osteogenic differentiation. Previously, BMP delivery has been designed and evaluated for osteogenic differentiation, focusing on carriers and sustained release system for delivery of BMPs. The effect of the delivery mode in cell culture plate on osteogenic differentiation potential was not evaluated. Herein, to investigate the effect of delivery mode on osteogenic differentiation of BM-MSCs in this study, we fabricated bottom-up release and top-down release systems for culture plate delivery of BMP-2. And also, we selected Arg-Gly-Asp- (RGD-) conjugated alginate hydrogel for BMP-2 delivery because alginate is able to release BMP-2 in a sustained manner and it is a biocompatible material. After 7 days of culture, the bottom-up release system in culture plate significantly stimulated alkaline phosphate activity of human bone marrow-mesenchymal stem cells. The present study highlights the potential value of the tool in stem cell therapy.
Keywords	Internal medicine ; RC31-1245
Subject code	571
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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