Chan-Sik Kim’s research while affiliated with Korea University of Science and Technology and other places

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Publications (113)


Efficacy and Safety of Useul for Dry Eye Disease: Protocol for a Randomized, Double-Blind, Placebo-Controlled, Parallel, Phase 2 Clinical Trial
  • Article
  • Full-text available

November 2024

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11 Reads

Healthcare

Yee-Ran Lyu

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O-Jin Kwon

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Bongkyun Park

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[...]

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Chan-Sik Kim

Introduction: Dry eye disease (DED) is a very frequently encountered ocular disease, making it a growing public health burden. However, current treatments for DED present unmet medical needs owing to their side effects or ineffectiveness. Therefore, an effective and safe therapeutic agent to manage DED is needed. Method and Analysis: We planned a phase 2, dose-finding, double-blind, randomized placebo-controlled trial to evaluate the efficacy and safety of two different doses of USL (Useul), the extract of Achyranthis Radix, compared with placebo, for DED. USL has been found to protect against DED by inducing tear secretion and improving corneal irregularity via anti-inflammatory effects, which will provide new therapeutic options. One hundred and twenty participants will be enrolled, after assessing the inclusion/exclusion criteria, at Daejeon University Daejeon Korean Medicine Hospital. Enrolled participants will be allocated to standard-dose USL, high-dose USL, or placebo groups in a 1:1:1 ratio and will be required to administer the trial medication twice a day for 12 weeks and visit the clinic five times. For efficacy outcomes, objective endpoints of fluorescein corneal staining score, tear break-up time, Schirmer’s test, and meibomian test and subjective endpoints of Ocular Surface Disease Index, visual analog scale, Standard Patient Evaluation for Eye Dryness-II, and biomarkers will be assessed throughout the trial. Safety will be assessed based on adverse events, vital signs, laboratory tests, visual acuity, and intraocular pressure. Discussion: Our study results are expected to provide clinical evidence for the use of DED as an effective and safe agent for DED.

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Achyranthis radix Extract Enhances Antioxidant Effect of Placenta-Derived Mesenchymal Stem Cell on Injured Human Ocular Cells

July 2024

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37 Reads

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2 Citations

Cells

Age-related ocular diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy are major causes of irreversible vision impairment in the elderly. Conventional treatments focus on symptom relief and disease slowdown, often involving surgery, but fall short of providing a cure, leading to substantial vision loss. Regenerative medicine, particularly mesenchymal stem cells (MSCs), holds promise for ocular disease treatment. This study investigates the synergistic potential of combining placenta-derived MSCs (PD-MSCs) with Achyranthis radix extract (ARE) from Achyranthes japonica to enhance therapeutic outcomes. In a 24-h treatment, ARE significantly increased the proliferative capacity of PD-MSCs and delayed their senescence (* p < 0.05). ARE also enhanced antioxidant capabilities and increased the expression of regeneration-associated genes in an in vitro injured model using chemical damages on human retinal pigment epithelial cell line (ARPE-19) (* p < 0.05). These results suggest that ARE-primed PD-MSC have the capability to enhance the activation of genes associated with regeneration in the injured eye via increasing antioxidant properties. Taken together, these findings support the conclusion that ARE-primed PD-MSC may serve as an enhanced source for stem cell-based therapy in ocular diseases.





Gene expression profiling of nasal inflammation induced by diesel particles using an in vivo system

February 2023

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17 Reads

Ecotoxicology and Environmental Safety

Korean diesel particulate matter 20 (KDP20) is a pollutant comprising a complex mixture of carbon and chemical irritants. Although particulate matter and nasal inflammation are strongly associated, the underlying molecular mechanism based on systematic transcriptome analysis remains unknown. In this study, genome-wide gene expression profiles of mouse nasal tissues were determined following exposure to KDP20 for 5 and 10 days and compared with those of the control (n = 4/group). We identified 758 significant differentially expressed genes (DEGs) and classified them as 5-day-specific, 10-day-specific, and common among groups based on their expression patterns. The terms "regulation of alpha-beta T cell differentiation," "macrophage differentiation," and "cell adhesion mediated by integrin" were significantly enriched in each group. Receiver operating characteristic analysis revealed six genes as potential predictive biomarkers. The differential expression of these six genes was validated using quantitative RT-PCR (n = 3/group). Furthermore, a possible mechanism for nasal inflammation was suggested through the binding analysis between metal ions and genes. The genes identified in this study may play important roles in regulating the mechanism of nasal inflammation induced by diesel particles, especially immune cell regulation, and may function as markers for diesel particle-induced nasal inflammation.


Expression of human IL-4, IL-5, IL-8, IL-13, IL-33, and TSLP mRNA in the human nasal mucosa. mRNA gene expression was measured via real time-polymerase chain reaction and presented as relative fold-changes to visit 1 sample. Data are presented as the mean ± standard deviation (n = 30). ∗p<0.01∗∗∗p<0.001. IL-4, interleukin 4; TSLP, thymic stromal lymphopoietin.
Generation of a PM-induced animal model and drug administration. KDP20, Korea diesel particulate matter; BYG, Biyeom-go; Nasonex, positive control; I.N., intervention; CTL, control.
Effects of BYG and Nasonex treatment on expression of goblet cells and inflammatory factors in KDP20-induced mice. (a) Generation of a KDP-induced animal model and drug administration. (b) Representative images of goblet cells with PAS staining of nasal tissues in KDP20-treated mice. PAS-positive cells were distributed in the nasal epithelium. (c–g) mRNA expression of immune biomarkers. NOR, negative control; KDP20, Korea diesel particulate matter; BYG, Biyeom-go; Nasonex, positive control; PAS, periodic acid-Schiff; IL-33, interleukin 33; TSLP, thymic stromal lymphopoietin; TNF-α, tumor necrosis factor-alpha.
Particulate Matter Exposure and the Changes in Immune Biomarkers: Effects of Biyeom-Go on the Nasal Mucosa of Patients with Allergic Rhinitis and a Particulate Matter-Treated Mouse Model

March 2022

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23 Reads

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4 Citations

Evidence-based Complementary and Alternative Medicine

This study was to investigate the effects of Biyeom-go (BYG, an herbal formula) on immune biomarkers present in the nasal mucosa of patients with allergic rhinitis under exposure to particulate matter 2.5 (PM2.5), and on changes in goblet cells and immune biomarkers in mice under exposure to Korea diesel particulate matter (KDP20). Thirty patients showing characteristic allergic rhinitis symptoms were enrolled in Jeonju-si, Korea, and treated with BYG thrice a day for four weeks. Changes in the expression of immune biomarkers (interleukin 4 (IL-4), IL-5, IL-8, IL-13, IL-33, and thymic stromal lymphopoietin (TSLP) mRNA), total nasal symptom scores (TNSS), mini-rhinitis-specific quality of life questionnaire (RQLQ) results, and visual analog scale scores were evaluated after 4 weeks of treatment. Additionally, the difference in PM2.5 concentrations in the air in Jeonju-si, Korea (November, 2019 ∼ March, 2020), was analyzed to determine the change in TNSS. KDP20 (100 μg/mL) was exposed to C57BL/6 mice for 10 days; 0.05% Nasonex (a positive control, mometasone furoate), or BYG was administrated for 5 days twice a day. The expression of inflammatory factors was detected via qRT-PCR using nasopharynx tissue samples of mice. BYG treatment was found to be associated with significant improvement in total nasal symptoms, especially itching and sneezing ( p < 0.0001 ), and mini-RQLQ after 4 weeks. IL-8 ( p < 0.01 ), IL-33 ( p < 0.01 ), and TSLP ( p < 0.001 ) expression levels decreased after BYG treatment. In mice, administration of BYG reduced the number of goblet cells increased through KDP20 treatment. KDP20-induced immune biomarkers (IL-33, TSLP, tumor necrosis factor alpha, and IL-8) were also significantly downregulated in the nasopharynx tissue after BYG treatment. Therefore, BYG may show therapeutic effects against allergic rhinitis in humans, and it was confirmed that the expression of PM-induced inflammatory factors in mice was decreased via BYG treatment.


Polycyclic aromatic hydrocarbons (PAHs) contents of KDP20 by gas chromatography mass spectrometry (GC-MS) analysis at a detection limit of 0.2 mg/kg
List of primers for qRT-PCR. Sequences are given from 5 to 3 . Normalized gene (beta-actin). PAHs exposure related gene (AHR2 and CYP1A). Oxidation related gene (CAT). Olfactory sensory neurons related gene (OMP and S100).
Damage to Olfactory Organs of Adult Zebrafish Induced by Diesel Particulate Matter

December 2021

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65 Reads

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6 Citations

International Journal of Molecular Sciences

Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes (AHR2 and CYP1A) were upregulated. Reactive oxidation stress (ROS) (CAT) and inflammation (IL-1B) related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes (OMP and S100) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.


Extract of Moutan radicis cortex and Cinnamomi ramulus ameliorates laser-induced choroidal neovascularization in Brown-Norway rats

October 2021

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24 Reads

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4 Citations

Phytomedicine

A B S T R A C T Background: Moutan radicis cortex (MRC) and Cinnamomi ramulus (CR) are commonly used in eastern Asian traditional medicine to treat various diseases including cerebrovascular and cardiovascular, and have wide spectrum of pharmacological activities. However, the effect against laser-induced choroidal neovascularization (CNV) of extract of MRC and CR (1:1) (MRCCR) has not yet been studied. Purpose: Our aim was to investigate the inhibitory effect of MRCCR on pathological CNV in laser-treated Brown-Norway (BN) rats. Methods: MRCCR (60, 90 mg/kg) was orally administered twice per day for 15 days from the day of CNV formation in laser-treated BN rats. Effects of MRCCR or its constituents on cell migration, tube formation, hyperpermeability and phosphorylation of FAK/p38 MAPK were confirmed in humane retinal microvascular endothelial cells or human retinal pigment epithelial cells. Results: MRCCR significantly reduced the CNV lesions areas and the extent of fluorescein leakage. MRCCR and its constituents such as ellagic acid, paeonol or gallic acid decreased cell migration, tube formation or hyperpermeability. MRCCR inhibited the phosphorylation of FAK and p38 MAPK. Conclusion: Combining the oral MRCCR and intravitreal injection of anti-VEGF medicine may result in a more potent therapeutic effect and consequently bring the reduction in eye injection numbers for patients with wet AMD.


Evaluation of oral toxicity and genotoxicity of Achyranthis Radix extract

March 2021

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19 Reads

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10 Citations

Journal of Ethnopharmacology

Ethnopharmacological relevance The root of Achyranthes bidentata Blume, Achyranthis Radix (AR), is used as a traditional medicine ingredient in East Asia. It has anti-inflammatory, anti-oxidative, and anti-diabetic activities. Aim of the study In the present study, we aimed to evaluate the oral toxicity and genotoxicity of single-dose and 4-week repeated-doses of AR hot water extract (ARE), under the good laboratory practice principles. Materials and methods For oral toxicity studies, SD rats (n = 5 per sex and group) were administered ARE at concentrations of 500, 1000, and 2000 mg/kg/day once (single dose) or once per day for 4 weeks (repeated dose). The non-clinical genotoxicity study consisted of bacterial reverse mutation using Escherichia coli (WP2 uvrA) and Salmonella typhimurium (TA98, TA100, TA1535, and TA1537), in vitro chromosomal aberration test with Chinese hamster lung cells (CHL/IU), and in vivo mouse bone marrow micronucleus test using bone marrow cells collected from male ICR mice (n = 5) that were orally administered ARE. Results In the single-dose oral toxicity study, mortality and treatment-related changes in body weight were not observed throughout the study, and the lethal dose was estimated to be >2000 mg/kg in rats. In the 4-week repeated-dose oral toxicity study, ARE did not induce significant changes in body weight, organ weight, food intake, or hematological and serum biochemical parameters in any group. In the bacterial reverse mutation test, ARE did not induce gene mutations in any tested strain. In the chromosomal aberration test, ARE did not cause chromosomal aberrations. The micronucleus test showed no significant increase in the number of micronucleated polychromatic erythrocytes or the mean ratio of polychromatic to total erythrocytes. Conclusions These results showed that ARE does not induce oral toxicity and genotoxicity in the in vivo and in vitro test systems.


Citations (86)


... It is used in Korea's traditional medicine to treat hypertension, rheumatism, osteoarthritis, and as an analgesic and diuretic. Moreover, both in vitro and in vivo experiments have demonstrated that the A. japonica extract has various physiological properties, including anti-allergic, anti-inflammatory, antioxidant, arthritis alleviation, hepatoprotective, anti-osteoporosis and anti-cancer (Jung et al., 2007;Kim & Park, 2010;Bang et al., 2012;Jang et al., 2012;Lee et al., 2020Lee et al., , 2024Eun et al., 2021). ...

Reference:

Shoot organogenesis and plant regeneration of Achyranthes japonica
Achyranthis radix Extract Enhances Antioxidant Effect of Placenta-Derived Mesenchymal Stem Cell on Injured Human Ocular Cells

Cells

... Topology analysis of the PPI network indicated the signifcant involvement of the NF-κB signaling pathway and TLR signaling pathway in the efects of IN. NF-κB signaling pathway and the TLR signaling pathways are interrelated and play signifcant roles in infammatory responses [53]. TLR4 upregulated the expression of various cytokines and chemokines, facilitating the recruitment and proliferation of infammatory cells. ...

Isobavachin, a main bioavailable compound in Psoralea corylifolia, alleviates lipopolysaccharide-induced inflammatory responses in macrophages and zebrafish by suppressing the MAPK and NF-κB signaling pathways
  • Citing Article
  • November 2023

Journal of Ethnopharmacology

... GO enrichment analysis was used to explore the distribution of the overall proteins and grasp the correlation between proteins and biological function in a whole [28][29][30]. In this study, GO enrichment analysis was applied to classify cellular components, biological process, molecular function, and KEGG pathway of the common protein targets between SQYG and AD. e results indicated that the common protein targets have multiple biological functions, including lipid localization, response to the metal ion of biological process, synapse part, neuronal cell body, GABA receptor complex of biological process, transmitter-gated ion channel activity, peptide binding, and acetylcholine binding of molecular function. ...

Particulate Matter Exposure and the Changes in Immune Biomarkers: Effects of Biyeom-Go on the Nasal Mucosa of Patients with Allergic Rhinitis and a Particulate Matter-Treated Mouse Model

Evidence-based Complementary and Alternative Medicine

... The DCFH-DA assay showed an increase in ROS production already from 100 mg L -1 exposure concentration after 72 and 120 h of exposure. Song et al. (2022) investigated the adverse effects induced by diesel dust rich in PAHs (especially fluoranthene, phenanthrene, and pyrene) and PTE (especially Fe, Zn, Mg, Al, Cu, Ni, Ti, and Hg) on D. rerio. The model organism was exposed in laboratory conditions to 300 mg L -1 of diesel dust, and oxidative stress was evaluated after 1, 2, 3, 7, and 10 days of exposure by quantifying CAT enzyme expression. ...

Damage to Olfactory Organs of Adult Zebrafish Induced by Diesel Particulate Matter

International Journal of Molecular Sciences

... MCE exerts anti-inflammatory effects by inhibiting the expression of iNOS and COX-2 through inactivation of the nuclear factor kappa B (NF-κB) pathway (Chun et al., 2007). In addition, MC can significantly reduce the area of laser-induced choroidal neovascularization lesions and the degree of fluorescein leakage, and components of MC (e.g., ellagic acid, paeonol, or gallic acid) reduce cell migration, tube formation, and hyperpermeability of retinal microvascular endothelial cells (Lee et al., 2022). Furthermore, MC has anticancer effects to inhibit the proliferation and invasion of bladder cancer cells and reduce size of bladder tumor without altering blood biochemical parameters in vivo (Lin et al., 2013). ...

Extract of Moutan radicis cortex and Cinnamomi ramulus ameliorates laser-induced choroidal neovascularization in Brown-Norway rats
  • Citing Article
  • October 2021

Phytomedicine

... Both drugs were manufactured as round and brown tablets. The dosage was determined based on the results of a previous experimental study that reported a lack of toxicity and genotoxicity of USL and the experimental study results, and USL was found to have no toxicity and genotoxicity in a previous study [29]. The standard-dose USL group will be administered one tablet of USL and one tablet of the placebo twice daily for 12 weeks; the high-dose USL group will be administered two tablets of USL twice daily for 12 weeks; and the control group will be administered two tablets of the placebo twice daily for 12 weeks. ...

Evaluation of oral toxicity and genotoxicity of Achyranthis Radix extract
  • Citing Article
  • March 2021

Journal of Ethnopharmacology

... Aster koraiensis Nakai (Synonym: Gymnaster koraiensis, Compositae), a native Korean plant primarily cultivated for ornamental use, has shown various pharmacological properties, such as anti-oxidant, anti-cancer, anti-inflammation, and hepatoprotective effects [14][15][16][17]. This plant also exhibits acyl CoA:cholesterol acyltransferase (ACAT) inhibition and affects the nuclear factor of activated T cell (NFAT) transcription factors [18,19]. ...

Antioxidant and α-Glucosidase Inhibitory Activities of the Extracts of Aster koraiensis Leaves
  • Citing Article
  • October 2018

Korean Journal of Medicinal Crop Science

... Both leucine-rich domains are critical for the peptide bonding sites, while the cysteine-rich domains are pivotal in the activation of EGFR. Therefore, EGFR has been well-known as one of the most targeted proteins in the early evaluation of anticancer agents [16]. Choe et al. [17] reported that EGFR protein has also been employed in the clinical trials of Tarceva® and Iressa® on non-small cell lung cancer patients. ...

Method for the Rapid Screening of Drug Candidates Using Single‐Protein Tracking in a Living Cell
  • Citing Article
  • December 2020

Bulletin of the Korean Chemical Society

... [Polygonaceae,Polygoni Cuspidati Rhizoma et Radix] (Named Huzhang in Traditional Chinese Medicine), another Chinese botanical drug, exhibits various pharmacological activities such as anti-inflammatory, antioxidant, metabolic modulation, microcirculation improvement, hepatoprotection, and immunity enhancement [9]. In recent years, a large number of studies [10][11][12] have demonstrated that the active metabolites of Reynoutria japonica Houtt. can exert therapeutic effects on NAFLD by improving insulin resistance, reducing oxidative stress, regulating lipid metabolism, improving endoplasmic reticulum stress, and reducing inflammatory infiltration. ...

POCU1b, the n-Butanol Soluble Fraction of Polygoni Cuspidati Rhizoma et Radix, Attenuates Obesity, Non-Alcoholic Fatty Liver, and Insulin Resistance via Inhibitions of Pancreatic Lipase, cAMP-Dependent PDE Activity, AMPK Activation, and SOCS-3 Suppression

... The application of biochars on an experimental basis to urban agriculture sites has been limited, with previous studies highlighting mixed results (Barrow, 2012;Werner et al, 2019). The potential role of biochar within urban farming practices highlights a smaller scale, and very targeted application of biochars (Song et al, 2020); many urban agriculture sites consist of small pockets of land, and diverse history and pollution legacy (Dennis et al, 2020). Here, biochar presents an opportunity to produce a soil amendment in situ and at the point of usage. ...

New application for assessment of dry eye syndrome induced by particulate matter exposure

Ecotoxicology and Environmental Safety