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Prof. Dr. Kyung-Min Lim
College of Pharmacy, Ewha Womans University, Seoul, Korea

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0 Anti-aging
0 Atopic Dermatitis
0 Cosmetics
0 Skin
0 Whitening

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Skin
irritation
Atopic Dermatitis
Cosmetics
Whitening
Alternative to animal test methods
Anti-aging

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Journal article
Published: 30 July 2021 in Journal of Toxicology and Environmental Health, Part A
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As an alternative to in vivo Draize rabbit eye irritation test, this study aimed to construct an in silico model to predict the complete United Nations (UN) Globally Harmonized System (GHS) for classification and labeling of chemicals for eye irritation category [eye damage (Category 1), irritating to eye (Category 2) and nonirritating (No category)] of liquid chemicals with Integrated approaches to testing and assessment (IATA)-like two-stage random forest approach. Liquid chemicals (n = 219) with 34 physicochemical descriptors and quality in vivo data were collected with no missing values. Seven machine learning algorithms (Naive Bayes, Logistic Regression, First Large Margin, Neural Net, Random Forest (RF), Gradient Boosted Tree, and Support Vector Machine) were examined for the ternary categorization of eye irritation potential at a single run through 10-fold cross-validation. RF, which performed best, was further improved by applying the ‘Bottom-up approach’ concept of IATA, namely, separating No category first, and discriminating Category 1 from 2, thereafter. The best performing training dataset achieved an overall accuracy of 73% and the correct prediction for Category 1, 2, and No category was 80%, 50%, and 77%, respectively for the test dataset. This prediction model was further validated with an external dataset of 28 chemicals, for which an overall accuracy of 71% was achieved.

ACS Style

Yeonsoo Kang; Boram Jeong; Doo-Hyeon Lim; Donghwan Lee; Kyung-Min Lim. In silico prediction of the full United Nations Globally Harmonized System eye irritation categories of liquid chemicals by IATA-like bottom-up approach of random forest method. Journal of Toxicology and Environmental Health, Part A 2021, 1 -13.

AMA Style

Yeonsoo Kang, Boram Jeong, Doo-Hyeon Lim, Donghwan Lee, Kyung-Min Lim. In silico prediction of the full United Nations Globally Harmonized System eye irritation categories of liquid chemicals by IATA-like bottom-up approach of random forest method. Journal of Toxicology and Environmental Health, Part A. 2021; ():1-13.

Chicago/Turabian Style

Yeonsoo Kang; Boram Jeong; Doo-Hyeon Lim; Donghwan Lee; Kyung-Min Lim. 2021. "In silico prediction of the full United Nations Globally Harmonized System eye irritation categories of liquid chemicals by IATA-like bottom-up approach of random forest method." Journal of Toxicology and Environmental Health, Part A , no. : 1-13.

Review
Published: 08 June 2021 in International Journal of Molecular Sciences
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Hyper-activated melanocytes are the major cause of skin hyper-pigmentary disorders, such as freckles and melasma. Increasing efforts have been made to search for materials with depigmenting activity to develop functional cosmetics. As a result, numerous materials have been reported to have depigmenting activity but some of them are known to cause unwanted side effects. Consequently, anti-pigmentary natural compounds without concern of toxicity are in great demand. Virtually all sorts of natural sources have been investigated to find anti-pigmentary natural compounds. This review summarizes recently reported anti-pigmentary natural compounds and their mode of action from the ocean, plants, and bacteria.

ACS Style

Kyuri Kim; Yoonjung Huh; Kyung-Min Lim. Anti-Pigmentary Natural Compounds and Their Mode of Action. International Journal of Molecular Sciences 2021, 22, 6206 .

AMA Style

Kyuri Kim, Yoonjung Huh, Kyung-Min Lim. Anti-Pigmentary Natural Compounds and Their Mode of Action. International Journal of Molecular Sciences. 2021; 22 (12):6206.

Chicago/Turabian Style

Kyuri Kim; Yoonjung Huh; Kyung-Min Lim. 2021. "Anti-Pigmentary Natural Compounds and Their Mode of Action." International Journal of Molecular Sciences 22, no. 12: 6206.

Journal article
Published: 12 May 2021 in International Journal of Molecular Sciences
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With the rapid growth of the wireless communication industry, humans are extensively exposed to electromagnetic fields (EMF) comprised of radiofrequency (RF). The skin is considered the primary target of EMFs given its outermost location. Recent evidence suggests that extremely low frequency (ELF)-EMF can improve the efficacy of DNA repair in human cell-lines. However, the effects of EMF-RF on DNA damage remain unknown. Here, we investigated the impact of EMF-long term evolution (LTE, 1.762 GHz, 8 W/kg) irradiation on DNA double-strand break (DSB) using the murine melanoma cell line B16 and the human keratinocyte cell line HaCaT. EMF-LTE exposure alone did not affect cell viability or induce apoptosis or necrosis. In addition, DNA DSB damage, as determined by the neutral comet assay, was not induced by EMF-LTE irradiation. Of note, EMF-LTE exposure can attenuate the DNA DSB damage induced by physical and chemical DNA damaging agents (such as ionizing radiation (IR, 10 Gy) in HaCaT and B16 cells and bleomycin (BLM, 3 μM) in HaCaT cells and a human melanoma cell line MNT-1), suggesting that EMF-LTE promotes the repair of DNA DSB damage. The protective effect of EMF-LTE against DNA damage was further confirmed by attenuation of the DNA damage marker γ-H2AX after exposure to EMF-LTE in HaCaT and B16 cells. Most importantly, irradiation of EMF-LTE (1.76 GHz, 6 W/kg, 8 h/day) on mice in vivo for 4 weeks reduced the γ-H2AX level in the skin tissue, further supporting the protective effects of EMF-LTE against DNA DSB damage. Furthermore, p53, the master tumor-suppressor gene, was commonly upregulated by EMF-LTE irradiation in B16 and HaCaT cells. This finding suggests that p53 plays a role in the protective effect of EMF-LTE against DNA DSBs. Collectively, these results demonstrated that EMF-LTE might have a protective effect against DNA DSB damage in the skin, although further studies are necessary to understand its impact on human health.

ACS Style

Hee Jin; Kyuri Kim; Ga-Young Park; Minjeong Kim; Hae-June Lee; Sangbong Jeon; Ju Kim; Hak Kim; Kyung-Min Lim; Yun-Sil Lee. The Protective Effects of EMF-LTE against DNA Double-Strand Break Damage In Vitro and In Vivo. International Journal of Molecular Sciences 2021, 22, 5134 .

AMA Style

Hee Jin, Kyuri Kim, Ga-Young Park, Minjeong Kim, Hae-June Lee, Sangbong Jeon, Ju Kim, Hak Kim, Kyung-Min Lim, Yun-Sil Lee. The Protective Effects of EMF-LTE against DNA Double-Strand Break Damage In Vitro and In Vivo. International Journal of Molecular Sciences. 2021; 22 (10):5134.

Chicago/Turabian Style

Hee Jin; Kyuri Kim; Ga-Young Park; Minjeong Kim; Hae-June Lee; Sangbong Jeon; Ju Kim; Hak Kim; Kyung-Min Lim; Yun-Sil Lee. 2021. "The Protective Effects of EMF-LTE against DNA Double-Strand Break Damage In Vitro and In Vivo." International Journal of Molecular Sciences 22, no. 10: 5134.

Journal article
Published: 18 April 2021 in Toxics
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Flavoring agents are added to cigarettes to improve taste. There are mostly permitted food additives, but some of them are restricted for use in food, cosmetics, and toys, since they can cause allergic reactions. Previous studies have investigated the levels of flavoring agents in tobacco but none has focused on their content in filter tips and capsules. Moreover, no studies have assessed the risk of adding allergenic flavoring agents in cigarettes. Here, we developed and validated a simultaneous analysis method for 25 allergenic flavoring agents and menthol with gas chromatography–tandem mass spectrometry to determine levels of flavoring agents in the tobacco, filter tips, and capsules of 54 commercial cigarettes in Korea. All cigarettes contained at least one allergenic flavoring agent regardless of the inclusion of flavoring capsules. Importantly, the filter tips and the capsules contained higher levels of flavoring agents than tobacco, highlighting the importance of the quantification of flavoring agents in these parts of cigarettes. Nevertheless, the risk assessment based on their levels in cigarettes suggested that their exposure was maintained at a safe level. However, the risk assessed from maximum menthol, linalool, and cinnamaldehyde exceeded one-tenth of derived no-effect levels, suggesting the need for further studies on their risk to human health.

ACS Style

Dae Jang; Hyung Kim; Eun Pack; Ye Koo; Kyung Lim; Dal Choi. Development of a Method for Simultaneous Analysis of Allergenic Flavoring Agents in Cigarettes and Quantitative Risk Assessment for Consumer Safety. Toxics 2021, 9, 87 .

AMA Style

Dae Jang, Hyung Kim, Eun Pack, Ye Koo, Kyung Lim, Dal Choi. Development of a Method for Simultaneous Analysis of Allergenic Flavoring Agents in Cigarettes and Quantitative Risk Assessment for Consumer Safety. Toxics. 2021; 9 (4):87.

Chicago/Turabian Style

Dae Jang; Hyung Kim; Eun Pack; Ye Koo; Kyung Lim; Dal Choi. 2021. "Development of a Method for Simultaneous Analysis of Allergenic Flavoring Agents in Cigarettes and Quantitative Risk Assessment for Consumer Safety." Toxics 9, no. 4: 87.

Journal article
Published: 29 March 2021 in Science of The Total Environment
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Preservatives are essential additives in dishwashing detergents and wet wipes. Ensuring the safe use of preservatives in products is important for public health, as some preservatives are associated with health issues. In this study, the content of 12 preservatives in 105 dishwashing detergents and 105 wet wipes was determined, where these compounds are commonly found, among consumer products. A realistic exposure estimation was considered by using Korean consumer-specific exposure parameters for adults and babies. A probabilistic risk assessment was conducted by applying the Monte Carlo simulation method. Benzoic acid (41%) and cetylpyridinium chloride (30%) were the most commonly used preservatives in dishwashing detergents and wet wipes, respectively, although their content in different products (benzoic acid: 0.28–19.4 mg/g in dishwashing detergents; cetylpyridinium chloride: 0.003–0.64 mg/g in wet wipes) varied widely. The calculated median and upper-limit margin of safety (MOS) values related to systemic health effects and skin sensitization from exposure to preservatives largely exceeded the target MOS, which confirmed the safety of the products. Exposure to preservatives from wet wipes was several times higher in babies than in adults. Sensitivity analysis revealed that the amount of the product used, frequency of use, and weight fraction of the preservative were the major contributors to the exposure to preservatives from dishwashing detergents and wet wipes.

ACS Style

Eun Chul Pack; Ho Geon Lee; Dae Yong Jang; Hui Sun Sin; Tae Yong Kim; Hyung Soo Kim; Kyung Min Lim; Dal Woong Choi. Probabilistic risk assessment of preservatives in dishwashing detergents and wet wipes for Korean consumers. Science of The Total Environment 2021, 782, 146829 .

AMA Style

Eun Chul Pack, Ho Geon Lee, Dae Yong Jang, Hui Sun Sin, Tae Yong Kim, Hyung Soo Kim, Kyung Min Lim, Dal Woong Choi. Probabilistic risk assessment of preservatives in dishwashing detergents and wet wipes for Korean consumers. Science of The Total Environment. 2021; 782 ():146829.

Chicago/Turabian Style

Eun Chul Pack; Ho Geon Lee; Dae Yong Jang; Hui Sun Sin; Tae Yong Kim; Hyung Soo Kim; Kyung Min Lim; Dal Woong Choi. 2021. "Probabilistic risk assessment of preservatives in dishwashing detergents and wet wipes for Korean consumers." Science of The Total Environment 782, no. : 146829.

Editorial
Published: 16 March 2021 in International Journal of Molecular Sciences
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The skin epidermis is the outermost epithelial tissue that protects the body from the external environment

ACS Style

Kyung-Min Lim. Skin Epidermis and Barrier Function. International Journal of Molecular Sciences 2021, 22, 3035 .

AMA Style

Kyung-Min Lim. Skin Epidermis and Barrier Function. International Journal of Molecular Sciences. 2021; 22 (6):3035.

Chicago/Turabian Style

Kyung-Min Lim. 2021. "Skin Epidermis and Barrier Function." International Journal of Molecular Sciences 22, no. 6: 3035.

Journal article
Published: 04 March 2021 in International Journal of Molecular Sciences
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Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood–brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.

ACS Style

Donghyun Kim; Eun-Hye Kim; Sungbin Choi; Kyung-Min Lim; Lu Tie; Arshad Majid; Ok-Nam Bae. A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood–Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage. International Journal of Molecular Sciences 2021, 22, 2563 .

AMA Style

Donghyun Kim, Eun-Hye Kim, Sungbin Choi, Kyung-Min Lim, Lu Tie, Arshad Majid, Ok-Nam Bae. A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood–Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage. International Journal of Molecular Sciences. 2021; 22 (5):2563.

Chicago/Turabian Style

Donghyun Kim; Eun-Hye Kim; Sungbin Choi; Kyung-Min Lim; Lu Tie; Arshad Majid; Ok-Nam Bae. 2021. "A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood–Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage." International Journal of Molecular Sciences 22, no. 5: 2563.

Journal article
Published: 01 March 2021 in Biomolecules & Therapeutics
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Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

ACS Style

Minjeong Kim; Eugenia Jin Lee; Kyung-Min Lim. Ibuprofen Increases the Hepatotoxicity of Ethanol through Potentiating Oxidative Stress. Biomolecules & Therapeutics 2021, 29, 205 -210.

AMA Style

Minjeong Kim, Eugenia Jin Lee, Kyung-Min Lim. Ibuprofen Increases the Hepatotoxicity of Ethanol through Potentiating Oxidative Stress. Biomolecules & Therapeutics. 2021; 29 (2):205-210.

Chicago/Turabian Style

Minjeong Kim; Eugenia Jin Lee; Kyung-Min Lim. 2021. "Ibuprofen Increases the Hepatotoxicity of Ethanol through Potentiating Oxidative Stress." Biomolecules & Therapeutics 29, no. 2: 205-210.

Journal article
Published: 18 February 2021 in Food Control
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Ultraviolet (UV) sterilization of kitchenware is considered environmentally friendly and economical. However, there are many cases of extended UV irradiation, which raises concerns about the release of hazardous substances. Here, we investigated the migration of monomers, plastic additives, and non-intentionally added substances (NIAS) from food utensils made of melamine–formaldehyde resin into food simulants after UV irradiation for up to 7 d. The migration of monomers (melamine and formaldehyde) was analyzed using a high-performance liquid chromatograph with a diode array detector. When irradiated with a UV lamp for 7 d, the release of melamine from food utensils made of melamine–formaldehyde resins increased by up to 85-fold compared with that from the unexposed samples. Formaldehyde release increased up to 4-fold after UV exposure. UV exposure led to a sustained increase in melamine migration in a time-dependent manner. Formaldehyde release also increased on the first day, but plateaued after seven days of exposure. Safety assessment demonstrated that there is a low risk of melamine and formaldehyde exposure of up to 11.78% and 7.95%, respectively, compared with the tolerable daily intake. Non-target screening analysis of plastic additives and NIAS from melamine–formaldehyde resin and other synthetic resins was performed using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Exposure of melamine–formaldehyde resin to UV for 7 d drastically increased the release of plastic additives and NIAS. In contrast, for other synthetic resins (polypropylene, polyamide, polyethylene, polyethylene terephthalate, and silicone), the peaks of these compounds disappeared or decreased after UV exposure, indicating that the melamine–formaldehyde resin is less resistant to UV degradation than other synthetic resins.

ACS Style

Hyung Soo Kim; Ye Jin Lee; Ye Ji Koo; Eun Chul Pack; Kyung Min Lim; Dal Woong Choi. Migration of monomers, plastic additives, and non-intentionally added substances from food utensils made of melamine–formaldehyde resin following ultraviolet sterilization. Food Control 2021, 125, 107981 .

AMA Style

Hyung Soo Kim, Ye Jin Lee, Ye Ji Koo, Eun Chul Pack, Kyung Min Lim, Dal Woong Choi. Migration of monomers, plastic additives, and non-intentionally added substances from food utensils made of melamine–formaldehyde resin following ultraviolet sterilization. Food Control. 2021; 125 ():107981.

Chicago/Turabian Style

Hyung Soo Kim; Ye Jin Lee; Ye Ji Koo; Eun Chul Pack; Kyung Min Lim; Dal Woong Choi. 2021. "Migration of monomers, plastic additives, and non-intentionally added substances from food utensils made of melamine–formaldehyde resin following ultraviolet sterilization." Food Control 125, no. : 107981.

Journal article
Published: 15 February 2021 in Food and Chemical Toxicology
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Biocides are widely used in household products. Humans are exposed to biocides through dermal, inhalational, and oral routes. However, information on the dermal and inhalational toxicity of biocides is limited. We evaluated the effects of biocides on the skin and airways using the reconstructed human epidermis model KeraSkin™ and the airway model SoluAirway™. We determined the irritancy of 11 commonly used biocides (1,2-benzisothiazol-3(2H)-one [BIT], 2-phenoxyethanol [PE], zinc pyrithione, 2-bromo-2-nitropropane-1,3-diol, 3-iodoprop-2-ynyl N-butylcarbamate [IPBC], 2-octyl-1,2-thiazol-3-one, 2,2-dibromo-2-cyanoacetamide, 4-chloro-3-methylphenol [CC], 2-phenylphenol, deltamethrin, and 4,5-dichloro-2-octyl-1,2-thiazol-3-one) in the KeraSkin™ and SoluAirway™ by viability and histological examinations. BIT and CC were found to cause skin irritation at the approved concentrations or at the concentration close to approved limit while the others were non-irritants within the approved concentration. These results were confirmed via histology, wherein skin irritants induced erosion, vacuolation, and necrosis of the tissue. In the SoluAirway™, most of the biocides decreased cell viability even within the approved limits, except for PE, IPBC, and deltamethrin, suggesting that the airway may be more vulnerable to biocides than the skin. Taken together, our result indicates that some biocides can induce toxicity in skin and airway. Further studies on the dermal and inhalational toxicity of biocides are warranted.

ACS Style

Jee-Hyun Hwang; Haengdueng Jeong; Ye-On Jung; Ki Taek Nam; Kyung-Min Lim. Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models. Food and Chemical Toxicology 2021, 150, 112064 .

AMA Style

Jee-Hyun Hwang, Haengdueng Jeong, Ye-On Jung, Ki Taek Nam, Kyung-Min Lim. Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models. Food and Chemical Toxicology. 2021; 150 ():112064.

Chicago/Turabian Style

Jee-Hyun Hwang; Haengdueng Jeong; Ye-On Jung; Ki Taek Nam; Kyung-Min Lim. 2021. "Skin irritation and inhalation toxicity of biocides evaluated with reconstructed human epidermis and airway models." Food and Chemical Toxicology 150, no. : 112064.

Journal article
Published: 03 February 2021 in Toxics
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Biocides are commonly used as spray- or trigger-type formulations, thus dermal and respiratory exposure to biocide aerosol is unavoidable. However, little is known about the impact of aerosolization on the local toxicity of biocides on the skin or the airway. We compared the local toxicity of biocides after direct or aerosol exposure on reconstructed human skin epidermis and upper airway models. Three biocides, 1,2-benzisothiazol-3(2H)-one (BIT), 2-phenoxyethanol (PE), and 2-phenylphenol (OPP), most widely used in the market were selected. When the biocide was treated in aerosols, toxicity to the skin epidermis and upper airway tissue became significantly attenuated compared with the direct application as determined by the higher tissue viabilities. This was further confirmed in histological examination, wherein the tissue damages were less pronounced. LC-MS/MS and GC/MS analysis revealed that concentrations of biocides decreased during aerosolization. Importantly, the toxicity of biocides treated in 3 μm (median mass aerodynamic diameter (MMAD)) aerosols was stronger than that of 5 μm aerosol, suggesting that the aerosol particle size may affect biocide toxicity. Collectively, we demonstrated that aerosolization could affect the local toxicity of biocides on the skin epidermis and the upper airway.

ACS Style

Nahyun Lee; Dae Jang; Do Lee; Haengdueng Jeong; Ki Nam; Dal-Woong Choi; Kyung-Min Lim. Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models. Toxics 2021, 9, 29 .

AMA Style

Nahyun Lee, Dae Jang, Do Lee, Haengdueng Jeong, Ki Nam, Dal-Woong Choi, Kyung-Min Lim. Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models. Toxics. 2021; 9 (2):29.

Chicago/Turabian Style

Nahyun Lee; Dae Jang; Do Lee; Haengdueng Jeong; Ki Nam; Dal-Woong Choi; Kyung-Min Lim. 2021. "Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models." Toxics 9, no. 2: 29.

Review
Published: 18 January 2021 in Archives of Pharmacal Research
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Skin barrier dysfunction caused by endogenous or exogenous factors can lead to various disorders such as xerosis cutis, ichthyoses, and atopic dermatitis. Filaggrin is a pivotal structural protein of the stratum corneum (SC) and provides natural moisturizing factors that play a role in skin barrier functions. Filaggrin aggregates keratin filaments, resulting in the formation of a keratin network, which binds cornified envelopes and collapse keratinocytes to flattened corneocytes. This complex network contributes to the physical strength of the skin. Filaggrin is degraded by caspase-14, calpain 1, and bleomycin hydrolases into amino acids and amino acid metabolites such as trans-urocanic acid and pyrrolidone carboxylic acid, which are pivotal natural moisturizing factors in the SC. Accordingly, filaggrin is important for the pathophysiology of skin barrier disorders, and its deficiency or dysfunction leads to a variety of skin disorders. Here, the roles and biology of filaggrin, related skin diseases, and a therapeutic strategy targeting filaggrin are reviewed. In addition, several drug candidates of different mode of actions targeting filaggrin, along with their clinical efficacy, are discussed.

ACS Style

Yeonjoon Kim; Kyung-Min Lim. Skin barrier dysfunction and filaggrin. Archives of Pharmacal Research 2021, 44, 36 -48.

AMA Style

Yeonjoon Kim, Kyung-Min Lim. Skin barrier dysfunction and filaggrin. Archives of Pharmacal Research. 2021; 44 (1):36-48.

Chicago/Turabian Style

Yeonjoon Kim; Kyung-Min Lim. 2021. "Skin barrier dysfunction and filaggrin." Archives of Pharmacal Research 44, no. 1: 36-48.

Journal article
Published: 11 January 2021 in International Journal of Molecular Sciences
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Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1–10%), salicylic acid (0.2–2%), and lactobionic acid (1.2–12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50–80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

ACS Style

Jee-Hyun Hwang; Haengdueng Jeong; Nahyun Lee; Sumin Hur; Nakyum Lee; Jeong Jun Han; Hye Won Jang; Wang Keun Choi; Ki Taek Nam; Kyung-Min Lim. Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research. International Journal of Molecular Sciences 2021, 22, 657 .

AMA Style

Jee-Hyun Hwang, Haengdueng Jeong, Nahyun Lee, Sumin Hur, Nakyum Lee, Jeong Jun Han, Hye Won Jang, Wang Keun Choi, Ki Taek Nam, Kyung-Min Lim. Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research. International Journal of Molecular Sciences. 2021; 22 (2):657.

Chicago/Turabian Style

Jee-Hyun Hwang; Haengdueng Jeong; Nahyun Lee; Sumin Hur; Nakyum Lee; Jeong Jun Han; Hye Won Jang; Wang Keun Choi; Ki Taek Nam; Kyung-Min Lim. 2021. "Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research." International Journal of Molecular Sciences 22, no. 2: 657.

Journal article
Published: 01 January 2021 in Biomolecules & Therapeutics
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). The chemical structure was established through the interpretation of MS, UV, and NMR spectroscopic data. Antaroide is a nine-membered macrolide with lactone and lactam moieties. To investigate its applicability in skin whitening cosmetics, its anti-melanogenic activity in B16F10 murine melanoma cells was examined. As a result, antaroide displayed strong inhibitory activities against melanin synthesis and also attenuated the dendrite formation induced by the α-melanocyte stimulating hormone (α-MSH). Antaroide suppressed the mRNA expression of the melanogenic enzymes such as tyrosinase, TRP-1 and TRP-2. This suggests that it may serve as a transcriptional regulator of melanogenesis. Collectively, the discovery of this novel natural nine-membered macrolide and its anti-melanogenic activity could give new insights for the development of skin whitening agents.

ACS Style

Min-Ji Ryu; Eun-Ki Baek; Soyeon Kim; Chi Nam Seong; Inho Yang; Kyung-Min Lim; Sang-Jip Nam. Antaroide, a Novel Natural Nine-Membered Macrolide, Inhibits Melanin Biosynthesis in B16F10 Murine Melanoma Cells. Biomolecules & Therapeutics 2021, 29, 98 -103.

AMA Style

Min-Ji Ryu, Eun-Ki Baek, Soyeon Kim, Chi Nam Seong, Inho Yang, Kyung-Min Lim, Sang-Jip Nam. Antaroide, a Novel Natural Nine-Membered Macrolide, Inhibits Melanin Biosynthesis in B16F10 Murine Melanoma Cells. Biomolecules & Therapeutics. 2021; 29 (1):98-103.

Chicago/Turabian Style

Min-Ji Ryu; Eun-Ki Baek; Soyeon Kim; Chi Nam Seong; Inho Yang; Kyung-Min Lim; Sang-Jip Nam. 2021. "Antaroide, a Novel Natural Nine-Membered Macrolide, Inhibits Melanin Biosynthesis in B16F10 Murine Melanoma Cells." Biomolecules & Therapeutics 29, no. 1: 98-103.

Journal article
Published: 26 December 2020 in International Journal of Molecular Sciences
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With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition.

ACS Style

Kyuri Kim; Young Seung Lee; Nam Kim; Hyung-Do Choi; Dong-Jun Kang; Hak Rim Kim; Kyung-Min Lim. Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro. International Journal of Molecular Sciences 2020, 22, 170 .

AMA Style

Kyuri Kim, Young Seung Lee, Nam Kim, Hyung-Do Choi, Dong-Jun Kang, Hak Rim Kim, Kyung-Min Lim. Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro. International Journal of Molecular Sciences. 2020; 22 (1):170.

Chicago/Turabian Style

Kyuri Kim; Young Seung Lee; Nam Kim; Hyung-Do Choi; Dong-Jun Kang; Hak Rim Kim; Kyung-Min Lim. 2020. "Effects of Electromagnetic Waves with LTE and 5G Bandwidth on the Skin Pigmentation In Vitro." International Journal of Molecular Sciences 22, no. 1: 170.

Journal article
Published: 10 December 2020 in Molecules
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Lycii Fructus is a traditional medicine used to prevent liver and kidney diseases, which commonly derives from Lycium chinense and Lycium barbarum. Here, the extracts and ethyl acetate-soluble fractions of L. chinense fruits exhibited better hepatoprotective effects than those of L. barbarum, which was likely due to differences in their composition. Therefore, GC-MS and HPLC analyses were conducted to characterize the metabolite differences between L. chinense and L. barbarum. Based on amino acid (AA) and phenolic acid (PA) profiling, 24 AAs and 9 PAs were identified in the two species. Moreover, each species exhibited unique and readily distinguishable AA and PA star graphic patterns. HPLC analysis elucidated composition differences between the ethyl acetate-soluble layers of the two compounds. Further, NMR analysis identified their chemical structures as 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid and p-coumaric acid. The higher content of 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid was detected in L. chinense, whereas the content of p-coumaric acid was higher in L. barbarum. Therefore, the differences in the relative contents of these two secondary metabolites in the ethyl acetate-soluble layer of Lycii Fructus could be a good marker to discriminate between L. chinense and L. barbarum.

ACS Style

Min-Ji Ryu; Minjeong Kim; Moongi Ji; Chaeyoung Lee; Inho Yang; Seong-Bin Hong; Jungwook Chin; Eun Kyoung Seo; Man-Jeong Paik; Kyung-Min Lim; Sang-Jip Nam. Discrimination of Lycium chinense and L. barbarum Based on Metabolite Analysis and Hepatoprotective Activity. Molecules 2020, 25, 5835 .

AMA Style

Min-Ji Ryu, Minjeong Kim, Moongi Ji, Chaeyoung Lee, Inho Yang, Seong-Bin Hong, Jungwook Chin, Eun Kyoung Seo, Man-Jeong Paik, Kyung-Min Lim, Sang-Jip Nam. Discrimination of Lycium chinense and L. barbarum Based on Metabolite Analysis and Hepatoprotective Activity. Molecules. 2020; 25 (24):5835.

Chicago/Turabian Style

Min-Ji Ryu; Minjeong Kim; Moongi Ji; Chaeyoung Lee; Inho Yang; Seong-Bin Hong; Jungwook Chin; Eun Kyoung Seo; Man-Jeong Paik; Kyung-Min Lim; Sang-Jip Nam. 2020. "Discrimination of Lycium chinense and L. barbarum Based on Metabolite Analysis and Hepatoprotective Activity." Molecules 25, no. 24: 5835.

Journal article
Published: 08 August 2020 in Toxicology in Vitro
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Skin irritation tests using reconstructed human epidermis (RhE) employ viability as an endpoint, but color interference or borderline results are often problematic. We examined whether the cytology of cells from treated RhE could determine skin irritancy. Six chemicals (three irritants; DnP, 1-B, pH, three non-irritants; DP, APA, HS) were evaluated in a RhE, Keraskin™. DP, HS, and PH were clearly classified with viability, but DnP, 1-B, and APA were often falsely determined, due to borderline values falling near the cutoff, 50%. In histology, the tissues treated with DnP, 1-B, and PH showed erosion of the stratum corneum, vacuolization, and necrosis in the basal layer. DP- and HS-treated tissues showed relatively normal morphology but APA induced necrosis similar to irritants. Cytology revealed that DnP, 1-B or PH depleted cells and induced irregular and abnormal cell shapes. In contrast, relatively regular and normal shapes and clear distinction between the nucleus and cytoplasm was observed for DP, APA and HS. To further confirm it, additional 10 substances, including false positives from OECD TG 439, were tested. Overall (16 substances in total), cytology: total area predicted the skin irritancy of test chemicals with the highest accuracy (87.5%) followed by cytology: cell count (81.3%), histology (75%) and viability (68.8%), confirming the utility of cytology as an alternative endpoint in the skin irritation test using RhE.

ACS Style

Jee-Hyun Hwang; Haengdueng Jeong; Sumin Hur; Ki Taek Nam; Kyung-Min Lim. Employment of cytology for in vitro skin irritation test using a reconstructed human epidermis model, Keraskin™. Toxicology in Vitro 2020, 69, 104962 .

AMA Style

Jee-Hyun Hwang, Haengdueng Jeong, Sumin Hur, Ki Taek Nam, Kyung-Min Lim. Employment of cytology for in vitro skin irritation test using a reconstructed human epidermis model, Keraskin™. Toxicology in Vitro. 2020; 69 ():104962.

Chicago/Turabian Style

Jee-Hyun Hwang; Haengdueng Jeong; Sumin Hur; Ki Taek Nam; Kyung-Min Lim. 2020. "Employment of cytology for in vitro skin irritation test using a reconstructed human epidermis model, Keraskin™." Toxicology in Vitro 69, no. : 104962.

Journal article
Published: 05 August 2020 in Food and Chemical Toxicology
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The effect of simulants, repeated use, washing, and oiling on the release of toxic metals from metallic kitchen utensils was investigated. The release of As, Cd, Cr, Ni, and Pb from kitchen utensils composed of stainless steel, aluminum, copper alloy, and cast iron into food simulants was quantified using inductively coupled plasma-mass spectrometry. The results show that this release of toxic metals was highly dependent on pH. Generally, the release of toxic metals tended to decrease with repeated use, and the release of Cr and Ni from stainless steel samples was significantly higher in the first test, compared to the third test. The washing conditions affected the release of As and Cr, whose release levels were higher when washing only with water and with a steel wool pad, respectively. Furthermore, oiling cast iron cookware reduced the release of As, Cd, Cr, and Ni into acidic simulants by 66%, 83%, 71%, and 15%, respectively. The margin of exposure (MOE) was calculated for each toxic metal; the calculated MOE values indicated that it is improbable that the current level of exposure from metallic kitchen utensils would pose a health risk in Korea.

ACS Style

Ye Ji Koo; Eun Chul Pack; Ye Jin Lee; Hyung Soo Kim; Dae Yong Jang; Seung Ha Lee; Young Soon Kim; Kyung Min Lim; Dal Woong Choi. Determination of toxic metal release from metallic kitchen utensils and their health risks. Food and Chemical Toxicology 2020, 145, 111651 .

AMA Style

Ye Ji Koo, Eun Chul Pack, Ye Jin Lee, Hyung Soo Kim, Dae Yong Jang, Seung Ha Lee, Young Soon Kim, Kyung Min Lim, Dal Woong Choi. Determination of toxic metal release from metallic kitchen utensils and their health risks. Food and Chemical Toxicology. 2020; 145 ():111651.

Chicago/Turabian Style

Ye Ji Koo; Eun Chul Pack; Ye Jin Lee; Hyung Soo Kim; Dae Yong Jang; Seung Ha Lee; Young Soon Kim; Kyung Min Lim; Dal Woong Choi. 2020. "Determination of toxic metal release from metallic kitchen utensils and their health risks." Food and Chemical Toxicology 145, no. : 111651.

Journal article
Published: 05 August 2020 in Regulatory Toxicology and Pharmacology
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We conducted a me-too validation study to confirm the reproducibility, reliability, and predictive capacity of KeraSkin™ skin irritation test (SIT) as a me-too method of OECD TG 439. With 20 reference chemicals, within-laboratory reproducibility (WLR) of KeraSkin™ SIT in the decision of irritant or non-irritant was 100%, 100%, and 95% while between-laboratory reproducibility (BLR) was 100%, which met the criteria of performance standard (PS, WLR≥90%, BLR≥80%). WLR and BLR were further confirmed with intra-class correlation (ICC, coefficients >0.950). WLR and BLR in raw data (viability) were also shown with a scatter plot and Bland-Altman plot. Comparison with existing VRMs with Bland-Altman plot, ICC and kappa statistics confirmed the compatibility of KeraSkin™ SIT with OECD TG 439. The predictive capacity of KeraSkin™ SIT was estimated with 20 reference chemicals (the sensitivity of 98.9%, the specificity of 70%, and the accuracy of 84.4%) and additional 46 chemicals (for 66 chemicals [20 + 46 chemicals, the sensitivity, specificity and accuracy: 95.2%, 82.2% and 86.4%]). The receiver operating characteristic (ROC) analysis suggested a potential improvement of the predictive capacity, especially sensitivity, when changing cut-off (50% → 60–75%). Collectively, the me-too validation study demonstrated that KeraSkin™ SIT can be a new me-too method for OECD TG 439.

ACS Style

Ju-Hee Han; Seolyeong Kim; Su-Hyun Lee; Jin-Sik Kim; Yu Jin Chang; Tae-Cheon Jeong; Mi-Jeong Kang; Tae-Sung Kim; Hae Seong Yoon; Ga Young Lee; Seungjin Bae; Kyung-Min Lim. Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439. Regulatory Toxicology and Pharmacology 2020, 117, 104725 .

AMA Style

Ju-Hee Han, Seolyeong Kim, Su-Hyun Lee, Jin-Sik Kim, Yu Jin Chang, Tae-Cheon Jeong, Mi-Jeong Kang, Tae-Sung Kim, Hae Seong Yoon, Ga Young Lee, Seungjin Bae, Kyung-Min Lim. Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439. Regulatory Toxicology and Pharmacology. 2020; 117 ():104725.

Chicago/Turabian Style

Ju-Hee Han; Seolyeong Kim; Su-Hyun Lee; Jin-Sik Kim; Yu Jin Chang; Tae-Cheon Jeong; Mi-Jeong Kang; Tae-Sung Kim; Hae Seong Yoon; Ga Young Lee; Seungjin Bae; Kyung-Min Lim. 2020. "Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439." Regulatory Toxicology and Pharmacology 117, no. : 104725.

Journal article
Published: 31 January 2020 in Toxicology and Applied Pharmacology
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Arsenic, an environmental contaminant in drinking water worldwide is well-established to increase cardiovascular diseases (CVDs) in humans. Of these, thrombotic events represent a major adverse effect associated with arsenic exposure, for which an abundance of epidemiological evidence exists. Platelet aggregation constitutes a pivotal step in thrombosis but arsenic alone doesn't induce aggregation and the mechanism underlying arsenic-induced thrombosis still remains unclear. Here we demonstrated that arsenic induces morphological changes of platelets, i.e., contraction and pseudopod projection, the primal events of platelet activation, which can increase platelet reactivity. Arsenite induced prominent platelet shape changes in a dose-dependent manner in freshly isolated human platelets. Of note, arsenite suppressed focal adhesion kinase (FAK) activity, which in turn activated RhoA, leading to altered actin assembly through LIMK activation, and subsequent cofilin inactivation. Arsenic-induced platelet shape change appeared to increase the sensitivity to thrombin and ADP-induced aggregation. Supporting this, latrunculin A, an inhibitor of actin-dynamics abolished it. Taken together, we demonstrated that arsenic induces cytoskeletal changes and shape changes of platelets through FAK-mediated alteration of actin dynamics, which renders platelets reactive to activating stimuli, ultimately contributing to increased thrombosis.

ACS Style

Keunyoung Kim; Eun-Kyung Shin; Jin-Ho Chung; Kyung-Min Lim. Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity. Toxicology and Applied Pharmacology 2020, 391, 114912 .

AMA Style

Keunyoung Kim, Eun-Kyung Shin, Jin-Ho Chung, Kyung-Min Lim. Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity. Toxicology and Applied Pharmacology. 2020; 391 ():114912.

Chicago/Turabian Style

Keunyoung Kim; Eun-Kyung Shin; Jin-Ho Chung; Kyung-Min Lim. 2020. "Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity." Toxicology and Applied Pharmacology 391, no. : 114912.