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51 results match your criteria: "CKD Research Institute[Affiliation]"
Metabolism
December 2024
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea; Biomedical Institute for Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea; Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:
Background: Diabetic retinopathy (DR), a major blindness cause in developed countries, is intricately linked to diabetes management and its duration. Here, we demonstrate that HDAC6 mediates NLRP3 inflammasome activation under diabetic conditions, leading to retinal inflammation and degeneration.
Methods: This study demonstrated the therapeutic effects of HDAC6 genetic ablation, pharmacological inhibition, and HDAC6-deficient bone marrow transplantation in a diabetes model induced by streptozotocin and a high-fat diet.
Arch Pharm Res
January 2024
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Korea.
Ocular diseases are a growing global concern and have a significant impact on the quality of life. Cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy are the most prevalent ocular diseases. Their prevalence and the global market size are also increasing.
View Article and Find Full Text PDFBrain
September 2023
Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan 49201, Korea.
The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A.
View Article and Find Full Text PDFBMB Rep
March 2023
Department of Biomedical Science, CHA University, Seongnam 13488; iPS Bio Inc., Seongnam 13488, Korea.
Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics.
View Article and Find Full Text PDFGut Liver
September 2023
Department of Internal Medicine and Institute of Gastroenterology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
Background/aims: The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function.
Methods: Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis.
Adv Biol (Weinh)
February 2022
Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Charcot-Marie-Tooth disease type 2D (CMT2D), is a hereditary peripheral neuropathy caused by mutations in the gene encoding glycyl-tRNA synthetase (GARS1). Here, human induced pluripotent stem cell (hiPSC)-based models of CMT2D bearing mutations in GARS1 and their use for the identification of predictive biomarkers amenable to therapeutic efficacy screening is described. Cultures containing spinal cord motor neurons generated from this line exhibit network activity marked by significant deficiencies in spontaneous action potential firing and burst fire behavior.
View Article and Find Full Text PDFCancer Gene Ther
July 2022
Laboratory of Toxicology, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Lung carcinoma is the main reason for cancer-associated deaths in the world. In a previous study, FCH domain only 1 (FCHo1) which is managed by protein kinase B (AKT), was shown to be activated in lung cancer. FCHo1 knockdown has previously been shown to cause cell death in lung cancer.
View Article and Find Full Text PDFSci Rep
July 2021
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood-brain barrier (BBB) integrity.
View Article and Find Full Text PDFArthritis Res Ther
July 2021
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Background: To investigate the effects of inhibiting histone deacetylase (HDAC) 6 on inflammatory responses and tissue-destructive functions of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).
Methods: FLS from RA patients were activated with interleukin (IL)-1β in the presence of increasing concentrations of M808, a novel specific HDAC6 inhibitor. Production of ILs, chemokines, and metalloproteinases (MMPs) was measured in ELISAs.
Br J Pharmacol
November 2020
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
Background And Purpose: Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. CMT type 1A (CMT1A) accounts for approximately 50% of CMT patients and is linked to PMP22 gene duplication. Histone deacetylase-6 (HDAC6) has pleiotropic effects, such as regulating lipid homeostasis and cellular stress.
View Article and Find Full Text PDFPharmacol Rep
February 2021
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea.
Background: Although tofacitinib has shown highly significant efficacy for rheumatoid arthritis (RA), there are still a considerable number of patients that are non-responders owing to its limited effectiveness and various adverse effects. Thus, alternative options with better efficacy and lower toxicity are desired. Here, M-134, a recently developed HDAC6 inhibitor, was examined for its therapeutic potential when combined with tofacitinib in a rat model of RA.
View Article and Find Full Text PDFPharmaceutics
November 2020
Department of Pharmaceutical Sciences, Woosuk University, Jeonbuk 55338, Korea.
Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively.
View Article and Find Full Text PDFArthritis Res Ther
July 2020
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
Objectives: Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA).
Methods: HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.
Nat Commun
May 2020
Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
The Legionella pneumophila Dot/Icm type IVB secretion system (T4BSS) is extremely versatile, translocating ~300 effector proteins into host cells. This specialized secretion system employs the Dot/Icm type IVB coupling protein (T4CP) complex, which includes IcmS, IcmW and LvgA, that are known to selectively assist the export of a subclass of effectors. Herein, the crystal structure of a four-subunit T4CP subcomplex bound to the effector protein VpdB reveals an interaction between LvgA and a linear motif in the C-terminus of VpdB.
View Article and Find Full Text PDFIUCrJ
March 2020
Department of Biological Science, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
SMC complexes play a central role in chromosome organization in all domains of life. The bacterial Smc-ScpAB complex is a three-subunit complex composed of Smc, ScpA and ScpB. ScpA bridges the two ATPase domains of the Smc homodimer, while ScpB, which belongs to the kite family of proteins, interacts with ScpA.
View Article and Find Full Text PDFInflamm Bowel Dis
May 2020
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Background: Selective blocking of HDAC6 has become a promising strategy in treating inflammatory bowel disease. CKD-506 is a novel isoform-selective inhibitor of histone deacetylase 6. The present study was performed to evaluate the effect of CKD-506 on the NF-κB signaling pathway in intestinal epithelial cells (IECs) and macrophages and on murine models of acute and chronic colitis.
View Article and Find Full Text PDFAging Cell
January 2020
Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
Alzheimer's disease (AD) is an age-related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline.
View Article and Find Full Text PDFDiabetes Res Clin Pract
May 2019
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. Electronic address:
Aims: The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs.
Methods: INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone.
Prostaglandins Leukot Essent Fatty Acids
February 2019
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. Electronic address:
Identification of the characterization of cysteinyl leukotrienes receptor (CysLTRs) could facilitate our understanding of these receptors' role in asthma. We aimed to investigate the localization and interactions of CysLTRs using a mouse model of asthma. BALB/c mice were administered ovalbumin (OVA) to induce allergic asthma.
View Article and Find Full Text PDFJ Toxicol Sci
January 2019
College of Pharmacy, Dankook University, Korea.
Cisplatin (CP) is an anti-cancer drug used for treatment of solid tumors, but the major adverse effect is drug-induced nephrotoxicity. The current study aimed to determine biomarkers that might predict nephrotoxicity induced by CP using serum or urinary proton nuclear magnetic resonance (H NMR) spectral data in male Sprague-Dawley (S-D) rats. CP (0, 0.
View Article and Find Full Text PDFSci Rep
November 2018
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease with an unknown etiology. Recently, it has been elucidated that dysregulated histone deacetylase (HDAC) activity is related to the pathogenesis of inflammatory and autoimmune diseases. Broad-spectrum HDAC inhibitors are effective for the treatment of allergy, cancer, and autoimmune diseases, but they have several adverse side effects.
View Article and Find Full Text PDFBiomed Chromatogr
February 2019
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk, South Korea.
Int J Pharm
October 2018
College of Pharmacy, Dongguk University, Gyeonggi, Republic of Korea. Electronic address:
CKD-519, a potent cholesteryl ester transfer protein (CETP) inhibitor, is a clinical candidate being developed for the treatment of dyslipidemia. It is considered a Biopharmaceutical Classification System II compound with low solubility and high permeability. The objective of this study was to develop early formulations focusing on the dissolution rate of the compound to achieve dose-dependent exposure.
View Article and Find Full Text PDFXenobiotica
July 2019
e Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk , Republic of Korea.
The purpose of this study was to evaluate the acute effect of a small molecule inhibitor of DGAT-1 on triglycerides (TG) and cholesterol in polygenic type 2 diabetic TallyHo/JngJ (TH) mice. PF-04620110, a potent and selective DGAT-1 inhibitor, was used as a model compound in this study and which was administered to TH and ICR mice. The concentration of the model compound that produced 50% of maximum lowering of TG level (IC) in TH mice was not significantly different from that in ICR mice, when estimated using the model-based pharmacokinetic and pharmacodynamic assay, a two-compartmental model and an indirect response model.
View Article and Find Full Text PDFMolecules
June 2018
Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea.
Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC values of honokiol for the metabolism of phenacetin and diclofenac were 8.
View Article and Find Full Text PDF