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Key mechanisms in alcohol-associated liver disease: hepatic ADH deficiency, dysregulated hepatic lipid metabolism, and nonoxidative ethanol metabolites

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American Journal of Physiology - Gastrointestinal and Liver Physiology 2025年第4期328卷 G426-G428页

作者： Park, Seol Hee Seo, Wonhyo Department of Companion Animal Health Hanyang Women’s University Seoul South Korea Graduate School of Pharmaceutical Sciences College of Pharmacy Ewha Womans University Seoul South Korea Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul South Korea

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The revolution of type I organic photosensitizers: current strategies and future directions

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Science Bulletin 2025年第8期70卷 1203-1206页

作者： Yang, Mengyao Zhou, Luyan Zhao, Yuan-Yuan Swamy, Kunemadihalli Mathada Kotraiah Chen, Aibing Yoon, Juyoung College of Chemical and Pharmaceutical Engineering Hebei University of Science and Technology Shijiazhuang050018 China Department of Chemistry and Nanoscience Ewha Womans University Seoul03760 Korea People's Democratic Rep Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul03760 Korea People's Democratic Rep

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Lipid Droplets-Targetable Fluorescent Probe for Monitoring Polarity Changes During Ferroptosis

SSRN

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SSRN 2025年

作者： Zhou, Yongqing Huang, Bing Wang, Yan Kim, Heejeong Yan, Mei Yoon, Juyoung School of Chemistry and Chemical Engineering University of Jinan Jinan250022 China Department of Chemistry and Nanoscience EwhaWomans University Seoul03760 Korea Republic of Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul03760 Korea Republic of

Ferroptosis, a form of regulated cell death driven by the accumulation of reactive oxygen species-induced lipid peroxide, has gained significant attention in various pathological contexts. Lipid droplets polarity may be affected and changed in the initiation and progression of ferroptosis. Therefore, developing a promising tool for high-fidelity fluorescence analysis and the early diagnosis of ferroptosis-associated diseases are very significant. Based on this, we prepared carefully two kinds of small-molecule fluorescent probes for detecting polarity. One of the fluorescent probes (PY-2), triphenylamine (an electron donor) and 3-benzofuranone (an electron acceptor) were effectively linked via a π bridge. In vitro experiments, the two probes only showed high selectivity for environmental polarity over viscosity. The PY-2 precisely accumulated within lipid droplets in the colocation experiments, owing to its unique structural design. Additionally, the PY-2 exhibited low cytotoxicity, making it an ideal candidate for visualizing lipid droplets behavior during ferroptosis. Overall, this study offers develop a novel lipid droplets-targeting fluorescent probe PY-2 to monitor polarity variations during ferroptosis. © 2025, The Authors. All rights reserved.

关键词： Cell death

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Targeting the HER2-ELF3-KRAS axis: a novel therapeutic strategy for KRAS^G13D colorectal cancer

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Molecular Cancer 2025年第1期24卷 1-22页

作者： Hwang, Soo-Yeon Seo, Yoojeong Park, Seojeong Kim, Seul-Ah Moon, Inhye Liu, Yi Kim, Seojeong Pak, Eun Seon Jung, Sehyun Kim, Hyeyoon Jeon, Kyung-Hwa Seo, Seung Hee Sung, Inyoung Lee, Heetak Park, So-Yeon Na, Younghwa Kim, Tae Il Kwon, Youngjoo College of Pharmacy Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 South Korea Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul 03760 South Korea Division of Gastroenterology Department of Internal Medicine Yonsei University College of Medicine 50 Yonseiro Seodaemun-Gu Seoul 03722 South Korea BK21 FOUR Intelligence Computing Seoul National University Seoul South Korea Center for Genome Engineering Institute for Basic Science 55 Expo-Ro Yuseong-Gu Daejeon 34126 South Korea College of Pharmacy CHA University Pocheon 11160 South Korea

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRAS^G13D-mutated CRCs. We identified a novel transcriptional regulatory network involving HER2, ELF3, and KRAS, with ELF3 acting as a key transcription factor (TF) that regulates KRAS expression under conditions of HER2 overexpression. Our findings reveal that this HER2-ELF3-KRAS axis is exclusively activated in KRAS^G13D, driving aggressive oncogenic features and conferring resistance to cetuximab (CTX) therapy. Through comprehensive analysis of gene expression profiles, we demonstrated that HER2 is a crucial therapeutic target specifically for KRAS^G13D CRCs. To explore this further, we introduced YK1, a small molecule inhibitor designed to disrupt the ELF3-MED23 interaction, leading to the transcriptional downregulation of HER2 and KRAS. This intervention significantly attenuated the HER2-ELF3-KRAS axis, sensitizing KRAS^G13D CRCs to CTX and reducing their tumorigenic potential by inhibiting the epithelial-to-mesenchymal transition process. Our study underscores the importance of HER2 as a key determinant in the unique biological characteristics of KRAS^G13D CRCs and highlights the therapeutic potential of targeting the HER2-ELF3-KRAS axis. By presenting YK1 as a novel pharmacological approach, we provide a promising strategy for developing tailored interventions for KRAS^G13D CRCs, contributing to the ongoing efforts in precision medicine for CRCs. © The Author(s) 2025.

关键词： Colorectal cancer ELF3 HER2 HER2-ELF3-KRAS axis KRAS mutation KRASG13D Protein–protein interaction inhibitor Transcriptional regulation

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SMEPPI: An indenone derivative that selectively inhibits M1 macrophage activation and enhances phagocytic activity

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Biomedicine and Pharmacotherapy 2025年 183卷 117856-117856页

作者： Oh, Ji Hyun Jeong, Mi Gyeong Lee, Soheun Lim, Jihae Kang, Jio Bae, Myung Ae Ahn, Jin-Hee Hong, Jeong-Ho Hwang, Eun Sook College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul 03760 South Korea Gradutate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul 03760 South Korea Drug Discovery Platform Research Center Korea Research Institute of Chemical Technology (KRICT) Daejeon 34114 South Korea Department of Chemistry Gwangju Institute of Science and Technology Gwangju 61005 South Korea Division of Life Sciences Korea University Seoul 02841 South Korea

SMEPPI is a small molecule synthesized as a derivative of KR-62980 that has anti-diabetic and anti-inflammatory activities. Despite the established physiological effects of KR-62980, the effects and benefits of SMEPPI remain largely unexplored. This study investigated the immunomodulatory functions of SMEPPI on macrophages and inflammatory diseases. SMEPPI did not affect the differentiation and maturation of bone marrow-derived monocytes into macrophages, nor did it affect the proliferation of M1 or M2 macrophages. Although SMEPPI did not affect M2 macrophage polarization, it significantly inhibited IL-1β and IL-6 cytokine production in both M1 macrophages and activated RAW264.7 macrophages. Importantly, SMEPPI inhibited the expression and phosphorylation of NF-κB p65 through inhibition of Akt expression, preventing its translocation to the nucleus. It also promoted p65 degradation through the stimulation of the proteasomal degradation pathway by inducing the expression of proteasome-related genes, thereby inhibiting p65 transcriptional activity. SMEPPI also enhanced the expression of various molecules associated with macrophage phagocytosis, including CD68, CD33, and lectins, thereby increasing phagocytic activity. Moreover, SMEPPI mitigated lipopolysaccharides-induced acute lung injury by suppressing IL-1β and IL-6 production in M1 macrophages and reduced mortality related to severe lung injury. These findings indicate that SMEPPI effectively regulates inflammatory diseases by impeding p65-induced cytokine production and enhancement of phagocytosis by M1 macrophages. © 2025

关键词： Acute lung injury Macrophage Mortality P65 Phagocytosis SMEPPI

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Lipid droplets-targetable fluorescent probe for monitoring polarity changes during ferroptosis

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Dyes and Pigments 2025年 241卷

作者： Yongqing Zhou Bing Huang Yan Wang Heejeong Kim Mei Yan Juyoung Yoon School of Chemistry and Chemical Engineering University of Jinan Jinan 250022 People's Republic of China Department of Chemistry and Nanoscience EwhaWomans University Seoul 03760 South Korea Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul 03760 South Korea

Ferroptosis, a form of regulated cell death driven by the accumulation of reactive oxygen species-induced lipid peroxide, has gained significant attention in various pathological contexts. Lipid droplets polarity may be affected and changed in the initiation and progression of ferroptosis. Therefore, developing a promising tool for high-fidelity fluorescence analysis and the early diagnosis of ferroptosis-associated diseases are very significant. Based on this, we prepared carefully two kinds of small-molecule fluorescent probes for detecting polarity. One of the fluorescent probes (PY-2), triphenylamine (an electron donor) and 3-benzofuranone (an electron acceptor) were effectively linked via a π bridge. In vitro experiments, the two probes showed high selectivity for environmental polarity over viscosity. The PY-2 precisely accumulated within lipid droplets in the colocation experiments, owing to its unique structural design. Additionally, the PY-2 exhibited low cytotoxicity, making it an ideal candidate for visualizing lipid droplets behavior during ferroptosis. Overall, this study offers a novel lipid droplets-targeting fluorescent probe (PY-2) to monitor polarity variations of lipid droplets during ferroptosis.

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Dual Delivery of Light/Prodrug Nanoparticles Using Tumor-Implantable Micro Light-Emitting Diode on an Optofluidic System for Combinational Glioma Treatment

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ACS Nano 2025年 2025 Apr 28页

作者： Goo, Jagyeong Lee, Jun Seo Park, Junwon Jeon, Seong Ik Kim, Jeongrae Yun, Wan Su Shim, Nayeon Moon, Yujeong Song, Sunejeong Kim, Jinseong Cho, Hanhee Jeong, Ju Yeon Lee, Ju Seung Han, Sangheon Lee, Hyeon-Ju Koh, Won-Gun Chang, Won Seok Kim, Tae-Il Kim, Kwangmeyung Department of Chemical and Biomolecular Engineering Yonsei University 50 Yonsei-ro Seodaemun-gu Seoul03722 Korea Republic of 2066 Seobu-ro Jangan-gu Suwon16419 Korea Republic of Department of Neurosurgery Brain Research Institute College of Medicine Yonsei University 50-1 Yonsei-Ro Seodaemun-gu Seoul03722 Korea Republic of College of Pharmacy Graduate School of Pharmaceutical Sciences Ewha Womans University 52 Ewhayeodae-gil Seodaemun-gu Seoul03760 Korea Republic of KU-KIST Graduate School of Converging Science and Technology Korea University 145 Anam-ro Seongbuk-gu Seoul02841 Korea Republic of Gradutate Program in Innovative Biomaterials Convergence Ewha Womans University 52 Ewhayeodae-gil Seodaemun-gu Seoul03760 Korea Republic of

Glioma is a highly lethal tumor with a poor prognosis, in which the presence of the blood-brain barrier (BBB) and skull significantly limits treatment options. To address this, a tumor-implantable optofluidic system (LED-SC), consisting of a microsized LED (microLED) and a microsyringe chip (SC), is proposed to deliver both light and prodrug nanoparticles (PNPs) directly to brain glioma. The LED-SC combines microLED and SC to enable intratumoral administration of light and PNPs for chemophotodynamic therapy. PNPs, self-assembled nanoparticles of verteporfin (VPF)-doxorubicin (DOX) prodrug, are cleaved by the enzyme cathepsin B, releasing active drugs specifically within tumor cells. In vitro studies show that PNPs are taken up by glioma cells and exhibit enhanced cytotoxicity under light irradiation. The PNPs-loaded LED-SC can be implanted into glioma, wherein PNPs are slowly diffused through the tumor, bypassing the BBB, and it also ensures effective light delivery in glioma beneath the skull, boosting chemo-photodynamic therapy. In glioma mouse models, PNP-loaded LED-SC implantation showed a 3.9-fold improvement in PNP delivery efficiency over intravenous administration, leading to better drug distribution and therapeutic results. The PNPs-loaded LED-SC offers a promising and minimally invasive solution for glioma treatment, overcoming the barriers of the BBB and skull while reducing systemic toxicity. © 2025 American Chemical Society.

关键词： Controlled drug delivery

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Probabilistic risk assessment of emerging EU-regulated fragrance allergens in household and personal care products

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Environment International 2025年 200卷

作者： Hogeon Lee Eun Chul Pack Ye Ji Koo Dae Yong Jang Do Hyeon Lee Tae Hyeon An Gyeong Tae Kim Seung Ha Lee Kyung Min Lim Dalwoong Choi Transdisciplinary Major in Learning Health Systems Department of Health and Safety Convergence Science Graduate School Korea University Seoul Republic of Korea Health Science Research Center Korea University Seoul Republic of Korea College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University Seoul Republic of Korea Gradutate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul Republic of Korea

Fragrance allergens in consumer products are an emerging public health concern. In this study, 56 fragrance allergens—including 30 newly designated as mandatory labeling substances under Commission Regulation (EU) 2023/1545 of 26 July 2023 amending Regulation (EC) No. 1223/2009—were quantified for the first time in 267 household and personal care products available in South Korea. Quantification was performed using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC-MS). Of these allergens, 21 were detected exclusively in 119 kitchen cleaning products such as fruit and vegetable washes, dishwashing detergents, and dishwasher rinse aids, while none were found in disposable wipes. The most frequently detected substances were limonene, linalool, and α-terpineol. A tiered risk assessment was conducted based on the quantitative results to identify substances of concern for probabilistic risk assessment. In the conservative Tier 1 assessment, which considered systemic toxicity, skin sensitization, and local respiratory toxicity, five substances—limonene, benzyl alcohol, citral, hexyl cinnamal, and β-pinene—were flagged as potential concerns and further evaluated in a Tier 2 probabilistic risk assessment using Monte Carlo simulation. The Tier 2 assessment indicated no significant risk for systemic toxicity or skin sensitization, even at the 95th percentile exposure level. Sensitivity analysis identified key contributors to exposure variability: the concentration of the substance in the product, frequency and amount of use, and dilution rate. This study provides critical insight into exposure levels and potential health risks associated with newly regulated fragrance allergens in household and personal care products. The findings emphasize the need to update current safety management standards and demonstrate the value of probabilistic approaches in realistic risk assessments. By evaluating the safety of fragrance allergens in widely

关键词： Fragrance allergen Human risk assessment Household products Personal care products Sensitivity analysis AEL Acceptable Exposure Level CEL Calculated Exposure Level DST Dermal Sensitization Threshold ECHA European Chemicals Agency EI Electron Ionization EU European Union GC–MS Gas Chromatography–Mass Spectrometry HPLC High-Performance Liquid Chromatography ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use IFRA International Fragrance Association KNHANES Korea National Health and Nutrition Examination Survey LC-MS Liquid Chromatography–Mass Spectrometry LOD Limit of Detection LOQ Limit of Quantitation MFDS Ministry of Food and Drug Safety MOE Margin of Exposure NESIL No Expected Sensitization Induction Level NIER National Institute of Environmental Research NICS National Institute of Chemical Safety NOAEL No Observed Adverse Effect Level OECD Organisation for Economic Co-operation and Development POD Point of Departure PTFE polytetrafluoroethylene QSAR Quantitative Structure–Activity Relationship QRA Quantitative Risk Assessment RIFM Research Institute for Fragrance Materials SAF Sensitization Assessment Factor SIM Selected Ion Monitoring S/N Signal-to-Noise SCCNFP Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers SCCS Scientific Committee on Consumer Safety TTC Threshold of Toxicological Concern VP vapor pressure p-BMHCA Butylphenyl methylpropional HICC hydroxyisohexyl-3-cyclohexene carboxaldehyde DMBCA dimethyl phenethyl acetate OTNE tetramethylacetyloctahydronaphthalene HHCB Hexamethylindanopyran

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Stimuli-responsive smart nanomaterials for theranostics of urological cancers

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Coordination Chemistry Reviews 2025年 539卷

作者： Xu, Yi Moradialvand, Madineh Sala, Francesca Della Zare, Ehsan Nazarzadeh Hushmandi, Kiavash Rahimmanesh, Ilnaz Borzacchiello, Assunta Iravani, Siavash Zare, Iman Shin, Jungah Yoon, Juyoung Kang, Heemin Makvandi, Pooyan Department of Urology Department of Science & Technology Nano Medical Innovation & Collaboration Group (NMICG) The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People's Hospital Quzhou 324000 China The Quzhou Affiliated Hospital of Wenzhou Medical University Quzhou People's Hospital Quzhou 324000 China Center for Theoretical Physics Khazar University 41 Mehseti Street Baku AZ1096 Azerbaijan Institute of Polymers Composites and Biomaterials National Research Council (IPCB-CNR) Viale J.F. Kennedy 54 Naples 80125 Italy School of Chemistry Damghan University Damghan 36716-45667 Iran Nephrology and Urology Research Center Clinical Sciences Institute Baqiyatallah University of Medical Sciences Tehran Iran Applied Physiology Research Center Cardiovascular Research Institute Isfahan University of Medical Sciences Isfahan Iran W Nazar ST Boostan Ave Isfahan Iran Research and Development Department Sina Medical Biochemistry Technologies Co. Ltd. Shiraz *** Iran Department of Materials Science and Engineering Korea University Seoul 02841 South Korea Department of Chemistry and Nanoscience Ewha Womans University Seoul 03760 South Korea Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul 03760 South Korea College of Medicine Korea University Seoul 02841 South Korea

Urological cancers, including prostate, bladder, and kidney cancers, contribute significantly to the global burden of cancer-related mortality. While numerous reviews have addressed these cancers individually, this is the first comprehensive review that exclusively focuses specifically on nanotheranostics as a transformative approach for urological cancer. The distinct tumor microenvironments (TMEs) associated with these cancers pose both challenges and opportunities for precise nanotherapeutic interventions. This review provides a thorough examination of current advancements in nanotechnology-based diagnostics and therapeutics tailored to urological cancers. For each primary urological cancer type, we outline key strategies for leveraging nanotheranostics in the detection and treatment of tumors. Furthermore, we address the persisting challenges in enhancing tumor specificity and treatment efficacy. In essence, nanotheranostics offer a promising therapeutic avenue for urological cancers by enabling targeted drug delivery and controlled release of therapeutics within the tumor microenvironment. The objective of this pioneering review is to underscore recent developments and future prospects in utilizing nanotechnology to meet the unmet needs in the diagnosis and treatment of urological cancers. © 2025 Elsevier B.V.

关键词： Bladder Kidney cancers Nanocarriers Nanomaterials Prostate tumor Urological cancers

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Nanodrug delivery system for precision treatment of pulmonary fibrosis

Precision Medicine and Engineering

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Precision Medicine and Engineering 2025年第2期2卷

作者： Xiner Yi Xinru Zhang Yuanye Guan Yizhe Sha Xiaoliang Cheng Yonghyun Lee Wei-En Yuan Shanghai Frontiers Science Center of Drug Target Identification and Delivery School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai 200240 China Engineering Research Center of Cell & Therapeutic Antibody Ministry of Education and School of Pharmacy Shanghai Jiao Tong University Shanghai 200240 China National Key Laboratory of Innovative Immunotherapy Shanghai Jiao Tong University Shanghai 200240 China Inner Mongolia Research Institute of Shanghai Jiao Tong University Hohhot 010070 China Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China College of Pharmacy Ewha Womans University Seoul 03760 South Korea Graduate Program in Innovative Biomaterials Convergence Ewha Womans University Seoul 03760 South Korea

Pulmonary fibrosis (PF) is a chronic lung disease with high morbidity and mortality, complex pathological mechanisms and limited available treatments. Recently, the rapid development of nanotechnology has brought new hope for treating PF. Owing to their unique advantages in drug delivery, oxidative stress modulation, and gene protection, nanomaterials are capable of optimizing therapeutic efficacy and reversing side effects. In this review, the basic pathological mechanisms of PF are first introduced. Second, the application potential of various nanomaterials for treating PF is summarized. Finally, their advantages and challenges are discussed in detail, providing references for developing more promising and precise therapeutic strategies in the future.

关键词： Pulmonary fibrosis Idiopathic pulmonary fibrosis Nanomaterials Targeted drug delivery

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