👤 Chan-Hee Kim

A stilbenoid, rhapontigenin, isolated from the root of Rheum palmatum L. acts as a potent BACE1 inhibitor.

Jong Min Oh, Soo Hyun Kim, Bishnu Prasad Pandey +4 more · 2025 · Fitoterapia · Elsevier · added 2026-04-24

Jong Min Oh, Soo Hyun Kim, Bishnu Prasad Pandey, Woong-Hee Shin, Hyun Ju Son, Yun Ju Kwon, Hoon Kim Show less

Seven compounds, comprising three anthraquinones and four stilbenoids, were isolated from the roots of Rheum palmatum L. These compounds include chrysophanol (1), aloe-emodin (2), aloe-emodin 8-O-β-D- Show more

Seven compounds, comprising three anthraquinones and four stilbenoids, were isolated from the roots of Rheum palmatum L. These compounds include chrysophanol (1), aloe-emodin (2), aloe-emodin 8-O-β-D-glucopyranoside (3), desoxyrhapontigenin (4), rhapontigenin (5), desoxyrhaponticin (6), and piceatannol 3'-O-β-D-glucopyranoside (7). Among these, compound 5 showed potent β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activity with an IC Show less

no PDF DOI: 10.1016/j.fitote.2025.106484

RA-PR058, a novel ramalin derivative, reduces BACE1 expression and phosphorylation of tau in Alzheimer's disease mouse models.

Yongeun Cho, Jeongmi Lee, Jun-Sik Kim +20 more · 2025 · Animal cells and systems · Taylor & Francis · added 2026-04-24

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cognitive decline, anxiety-like behavior, β-amyloid (Aβ) accumulation, and tau hyperphosphorylation. BACE1, the Show more

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cognitive decline, anxiety-like behavior, β-amyloid (Aβ) accumulation, and tau hyperphosphorylation. BACE1, the enzyme critical for Aβ production, has been a major therapeutic target; however, direct BACE1 inhibition has been associated with adverse side effects. This study investigates the therapeutic potential of RA-PR058, a novel ramalin derivative, as a multi-targeted modulator of AD-related pathologies. The effects of RA-PR058 were evaluated Show less

📄 PDF DOI: 10.1080/19768354.2025.2459649

N

Jun-Sik Kim, Yongeun Cho, Jeongmi Lee +14 more · 2025 · Bioscience trends · added 2026-04-24

Jun-Sik Kim, Yongeun Cho, Jeongmi Lee, Heewon Cho, Sukmin Han, Yeongyeong Lee, Yeji Jeon, Tai Kyoung Kim, Ju-Mi Hong, Jeonghyeong Im, Minshik Chae, Yujeong Lee, Hyunwook Kim, Sang Yoon Park, Sung Hyun Kim, Joung Han Yim, Dong-Gyu Jo Show less

Alzheimer's disease (AD) is the most common type of dementia. Its incidence is rising rapidly as the global population ages, leading to a significant social and economic burden. AD involves complex pa Show more

Alzheimer's disease (AD) is the most common type of dementia. Its incidence is rising rapidly as the global population ages, leading to a significant social and economic burden. AD involves complex pathologies, including amyloid plaque accumulation, synaptic dysfunction, and neuroinflammation. This study explores the therapeutic potential of N Show less

no PDF DOI: 10.5582/bst.2024.01360

Bioinformatics and Deep Learning Approach to Discover Food-Derived Active Ingredients for Alzheimer's Disease Therapy.

Junyu Zhou, Chen Li, Yong Kwan Kim +1 more · 2025 · Foods (Basel, Switzerland) · MDPI · added 2026-04-24

Junyu Zhou, Chen Li, Yong Kwan Kim, Sunmin Park Show less

Alzheimer's disease (AD) prevention is a critical challenge for aging societies, necessitating the exploration of food ingredients and whole foods as potential therapeutic agents. This study aimed to Show more

Alzheimer's disease (AD) prevention is a critical challenge for aging societies, necessitating the exploration of food ingredients and whole foods as potential therapeutic agents. This study aimed to identify natural compounds (NCs) with therapeutic potential in AD using an innovative bioinformatics-integrated deep neural analysis approach, combining computational predictions with molecular docking and in vitro experiments for comprehensive evaluation. We employed the bioinformatics-integrated deep neural analysis of NCs for Disease Discovery (BioDeepNat) application in the data collected from chemical databases. Random forest regression models were utilized to predict the IC Show less

📄 PDF DOI: 10.3390/foods14010127

A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.

Seung-Hyun Baek, Suji Hong, Eunae Kim +16 more · 2025 · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · Wiley · added 2026-04-24

Seung-Hyun Baek, Suji Hong, Eunae Kim, Sunyoung Park, Minyoung Lee, Jinsu Park, Yoonsuk Cho, Hyunjun Yoon, Daeseung Kim, Youngkwang Yun, Youbin Kim, Yoonjung Choi, Keunsoo Kang, Sangyong Jung, Jun Pyo Kim, Eunha Kim, Sang Won Seo, Yong-Keun Jung, Dong-Gyu Jo Show less

β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation e Show more

β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology. The research reveals that the anticancer agent 6-thioguanosine (6-TG) markedly diminishes BACE1 expression without eliciting cytotoxicity while enhancing microglial phagocytic activity, and ameliorate cognitive impairments with reducing Aβ accumulation in AD mice. Leveraging advanced deep learning-based tool for target identification, and corroborating with surface plasmon resonance assays, it is elucidated that 6-TG directly interacts with RAGE, modulating BACE1 expression through the JAK2-STAT1 pathway and elevating soluble RAGE (sRAGE) levels in the brain. The findings illuminate the therapeutic potential of 6-TG in ameliorating AD manifestations and advocate for small molecule strategies to increase brain sRAGE levels, offering a strategic alternative to the challenges posed by the complexity of AD. Show less

📄 PDF DOI: 10.1002/advs.202407812

Natural compounds for Alzheimer's prevention and treatment: Integrating SELFormer-based computational screening with experimental validation.

Junyu Zhou, Yong Kwan Kim, Chen Li +1 more · 2025 · Computers in biology and medicine · Elsevier · added 2026-04-24

Junyu Zhou, Yong Kwan Kim, Chen Li, Sunmin Park Show less

This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict na Show more

This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict natural compounds (NCs) with potential in Alzheimer's disease (AD) treatment. The NCs were identified based on activity related to seven AD-specific genes, including acetylcholinesterase (AChE), amyloid precursor protein (APP), beta-secretase 1 (BACE1), and presenilin-1 (PSEN1). We implemented a computational pipeline using SELFormer and deep learning techniques, conducted optimal clustering and quantitative structure-activity relationship (QSAR) analyses, and performed a uniform manifold approximation and projection (UMAP) to categorize compounds based on bioactivity levels. Molecular docking analysis was carried out on selected compounds. To validate the computational predictions, we conducted in vitro studies using nerve growth factor (NGF)-differentiated PC12 cells. Finally, we mapped the relationships between food sources containing the identified compounds and their target proteins. Optimal clustering analysis revealed five distinct groups of NCs, while QSAR analysis highlighted variations in molecular properties across clusters. The UMAP projection identified 17 highly active NCs (pIC This integrated computational and experimental approach offers a promising framework for identifying potential NCs for AD treatment. The results contribute to exploring effective therapeutic strategies against AD. Show less

no PDF DOI: 10.1016/j.compbiomed.2024.109523

CBX1 as a Prognostic Biomarker and Therapeutic Target in Liver Hepatocellular Carcinoma: Insight into DNA Methylation and Non-Coding RNA Networks from Comprehensive Bioinformatics Analysis.

Hye-Ran Kim, Jongwan Kim · 2025 · Medicina (Kaunas, Lithuania) · MDPI · added 2026-04-24

📄 PDF DOI: 10.3390/medicina61060983

CBX1

Gene-Lifestyle Interactions in Renal Dysfunction: Polygenic Risk Modulation via Plant-Based Diets, Coffee Intake, and Bioactive Compound Interactions.

Meiling Liu, Da-Sol Kim, Sunmin Park · 2025 · Nutrients · MDPI · added 2026-04-24

📄 PDF DOI: 10.3390/nu17050916

CPS1

Comparative Analysis of the Total Proteome in Nonalcoholic Steatohepatitis: Identification of Potential Biomarkers.

Eda Ates, Hien Thi My Ong, Seung-Min Yu +2 more · 2025 · Molecular & cellular proteomics : MCP · Elsevier · added 2026-04-24

Eda Ates, Hien Thi My Ong, Seung-Min Yu, Ji-Hoon Kim, Min-Jung Kang Show less

Nonalcoholic fatty liver disease is a hepatic condition characterized by excessive fat accumulation in the liver with advanced stage nonalcoholic steatohepatitis (NASH), potentially leading to liver f Show more

Nonalcoholic fatty liver disease is a hepatic condition characterized by excessive fat accumulation in the liver with advanced stage nonalcoholic steatohepatitis (NASH), potentially leading to liver fibrosis, cirrhosis, and cancer. Currently, the identification and classification of NASH require invasive liver biopsy, which has certain limitations. Mass spectrometry-based proteomics can detect crucial proteins and pathways implicated in NASH development and progression. We collected the liver and serum samples from choline-deficient, L-amino acid-defined high-fat diet fed NASH C57BL/6J mice and human serum samples to examine proteomic alterations and identify early biomarkers for NASH diagnosis. In-depth targeted multiple reaction monitoring scanning and immunoblotting assays were used to verify the biomarker candidates from mouse liver and serum samples, and enzyme-linked immunosorbent assay (ELISA) was employed to analyze human serum samples. The multiple reaction monitoring analysis of NASH liver revealed 50 proteins with altered expression (21 upregulated and 29 downregulated) that are involved in biological processes such as detoxification, fibrosis, inflammation, and fatty acid metabolism. Ingenuity pathway analysis identified impaired protein synthesis, cellular stress and defense, cellular processes and communication, and metabolism in NASH mouse liver. Immunoblotting analysis confirmed that the expression of proteins associated with fatty acid metabolism (Aldo B and Fasn) and urea cycle (Arg1, Cps1, and Otc) was altered in the mouse liver and serum. Further analysis on human serum samples using ELISA confirmed the increased expression of multiple proteins, including Aldo B, Asl, and Lgals3, demonstrating values of 0.917, 0.979, and 0.965 of area under the curve in NASH diagnosis. These findings offer valuable insights into the molecular mechanisms of NASH and possible diagnostic biomarkers for early detection. Show less

📄 PDF DOI: 10.1016/j.mcpro.2025.100921

CPS1

Dhx36 deficiency accelerates BMSC senescence and promotes age-related bone loss.

Ji Sun Jang, Suhan Jung, Min-Kyoung Song +3 more · 2025 · BMB reports · added 2026-04-24

Ji Sun Jang, Suhan Jung, Min-Kyoung Song, Bongjun Kim, Zang Hee Lee, Hong-Hee Kim Show less

Senescence of mesenchymal stem cells in bone tissue (BMSCs), the primary progenitors of osteoblasts, is a key contributor to age-related osteopenia and osteoporosis. Aged cells exhibit elevated cellul Show more

Senescence of mesenchymal stem cells in bone tissue (BMSCs), the primary progenitors of osteoblasts, is a key contributor to age-related osteopenia and osteoporosis. Aged cells exhibit elevated cellular stress and abnormal accumulation of stress granules (SGs), which contain G-quadruplex (G4) structured nucleic acids and G4-binding proteins. Dhx36, a helicase that unwinds G4 structure, may play a protective role in this context. In this study, we investigated the function of Dhx36 in BMSCs and bone homeostasis by silencing Dhx36 expression in vitro and in vivo. Dhx36 deficiency increased SG formation and impaired their resolution in BMSCs. This was accompanied by reduced expression of G4-containing autophagyrelated genes and diminished autophagic activity. Loss of Dhx36 also enhanced senescence features and impaired BMSC osteogenic differentiation. Dhx36 expression was significantly lower in bone tissue and BMSCs from aged mice, compared to young mice. Moreover, 8-week-old mice with BMSC-specific Dhx36 knockout exhibited reduced bone volume and trabecular number, indicating premature bone loss. Analysis of public singlecell RNA sequencing data further showed that stress induced by 5-fluorouracil in mice suppressed Dhx36 expression in BMSCs, and downregulated genes related to ossification and osteoblast differentiation. Collectively, our findings identify Dhx36 as a regulator of BMSC aging, linking SG dynamics and autophagy to bone homeostasis, and suggest Dhx36 as a potential therapeutic target to prevent age-related bone loss. [BMB Reports 2025; 58(12): 501-510]. Show less

📄 PDF DOI: 10.5483/BMBRep.2025-0112

DHX36

Co-targeting KRAS and Exportin1 as an effective therapeutic strategy for KRASG12D mutant pancreatic ductal adenocarcinoma.

Husain Yar Khan, Mohammed Najeeb Al Hallak, Amro Aboukameel +29 more · 2025 · bioRxiv : the preprint server for biology · Cold Spring Harbor Laboratory · added 2026-04-24

Several KRASG12D inhibitors (KRASG12Di) are under clinical evaluation for pancreatic ductal adenocarcinoma (PDAC). However, as seen with other first generation KRAS inhibitors, resistance may limit th Show more

Several KRASG12D inhibitors (KRASG12Di) are under clinical evaluation for pancreatic ductal adenocarcinoma (PDAC). However, as seen with other first generation KRAS inhibitors, resistance may limit their long-term efficacy, necessitating combination strategies to enhance therapeutic outcomes. Exportin 1 (XPO1), a nuclear transport protein overexpressed in PDAC, represents a therapeutic vulnerability in KRAS-mutant cancers. Here, we demonstrate that the second-generation XPO1 inhibitor Eltanexor synergizes with MRTX1133 to enhance its efficacy in multiple PDAC models. We generated KRASG12Di-resistant PDAC cells and assessed their response to Eltanexor. The antiproliferative effects of MRTX1133 and Eltanexor combinations were evaluated in 2D and 3D Eltanexor sensitized MRTX1133-resistant PDAC cells to growth inhibition. In both 2D and 3D culture models, the combination of Eltanexor and MRTX1133 significantly reduced cell viability. Mechanistically, the combination treatment suppressed key KRAS downstream signaling molecules, including p-ERK, mTOR, p-4EBP1, DUSP6, and cyclin D1. Kinome analysis further revealed reduced MAPK-related kinase activity. Combining subtherapeutic doses of Eltanexor and MRTX1133 resulted in significant tumor regression and prolonged survival in PDAC xenograft and immunocompetent orthotopic allograft models. Moreover, maintenance therapy with Eltanexor prevented tumor relapse, yielding a durable antitumor response. This study demonstrates that Eltanexor overcomes resistance to MRTX1133 and enhances its efficacy in PDAC. The combination regimen may provide a durable therapeutic response while reducing the required dose of KRASG12D inhibitors, potentially delaying resistance and improving patient outcomes. Show less

📄 PDF DOI: 10.1101/2025.11.21.689857

DUSP6

Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity.

Z Zack Ma, Natalie J Guzikowski, Ji-Woon Kim +2 more · 2025 · Science (New York, N.Y.) · Science · added 2026-04-24

Z Zack Ma, Natalie J Guzikowski, Ji-Woon Kim, Ege T Kavalali, Lisa M Monteggia Show less

Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug's antidepressant action from a si Show more

Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug's antidepressant action from a single administration. Ketamine-induced synaptic potentiation at CA3-CA1 synapses has been proposed to be a key synaptic substrate for antidepressant action. Here, we found that ketamine-induced CA3-CA1 synaptic potentiation could be augmented by transiently increasing extracellular signal-regulated kinase (ERK) activity through pharmacological inhibition of dual-specificity phosphatases 6 (DUSP6). The antidepressant-like behavioral effects of acute ketamine treatment were extended by DUSP6 inhibition for up to 2 months. The selective deletion of tropomyosin receptor kinase B (TrkB) in excitatory neurons abolished these DUSP6 inhibition-mediated synaptic and behavioral effects. These data suggest that ketamine's rapid antidepressant effects can be sustained by selectively targeting downstream intracellular signaling. Show less

📄 PDF DOI: 10.1126/science.abb6748

DUSP6

Polyunsaturated Fatty Acids and Skin Cancer: Two-Sample Mendelian Randomization Study.

Gahyun Kim, Bo Ri Kim, Kyungho Paik +6 more · 2025 · Annals of dermatology · added 2026-04-24

Gahyun Kim, Bo Ri Kim, Kyungho Paik, Seon-Pil Jin, Hyunsun Park, Woojae Myung, Jin-Ku Lee, Chong Won Choi, Jinho Kim Show less

Observational studies have suggested associations between dietary polyunsaturated fatty acids (PUFAs) and cancer risk; however, causal inference regarding skin cancer remains limited due to potential Show more

Observational studies have suggested associations between dietary polyunsaturated fatty acids (PUFAs) and cancer risk; however, causal inference regarding skin cancer remains limited due to potential recall bias, confounding, and reverse causation. This study aimed to evaluate the causal association between genetically predicted circulating PUFA levels and the risk of skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We conducted a 2-sample Mendelian randomization (MR) study using genome-wide association study summary statistics from the UK Biobank (PUFAs, n=115,006) and the FinnGen consortium (BCC, n=26,272; SCC, n=4,663; melanoma, n=5,753). Genetic instruments were derived for omega-3, docosahexaenoic acid, omega-6, linoleic acid, and the omega-6:3 ratio. Multiple MR methods-including inverse-variance weighted, MR-Egger, weighted median, weighted mode, and MR-PRESSO-were applied to test for consistency and assess pleiotropy and heterogeneity. A higher genetically predicted linoleic acid to total fatty acid ratio was associated with a significantly lower risk of BCC and SCC. Conversely, higher genetically proxied serum omega-3 levels were associated with increased risks of BCC, SCC, and melanoma. The risk effect on SCC was attenuated upon exclusion of rs174528, a variant in the fatty acid desaturase 1 ( This MR analysis supports a causal role of circulating PUFAs in skin cancer development and highlights the importance of FADS-mediated endogenous PUFA metabolism. These findings provide novel insights into the genetic and metabolic underpinnings of skin cancer susceptibility. Show less

📄 PDF DOI: 10.5021/ad.25.095

Identification of Bone Metastasis-Related Gene Networks in Lung Cancer: Implications for Bone Metabolism.

Jungwoo Kim, Seong-Ho Park, Junho K Hur +1 more · 2025 · Journal of bone metabolism · added 2026-04-24

Jungwoo Kim, Seong-Ho Park, Junho K Hur, Sung Bae Park Show less

This study aimed to infer a causal gene network associated with bone metastasis in lung cancer and to validate its reliability through experimental gene expression analysis. Using DNA microarray data Show more

This study aimed to infer a causal gene network associated with bone metastasis in lung cancer and to validate its reliability through experimental gene expression analysis. Using DNA microarray data from the Gene Expression Omnibus, we analyzed samples from primary lung cancer and those with bone metastasis. Commonly expressed genes in both groups were identified, and a causal network was inferred using Bayesian network inference with Java Objects based on the Bayesian Dirichlet score. To evaluate the network, we predicted the expression changes of downstream genes following knockdown of a key upstream gene and compared these predictions with mRNA expression levels in fatty acid desaturase 1 (FADS1)-knockdown lung cancer cells. The genes FADS1, cardiotrophin-like cytokine factor 1 (CLCF1), chromosome 4 open reading frame 48, sushi, nidogen and EGF like domains 1, FK506-binding protein 15, and coenzyme Q10A (COQ10A) were identified as directly associated with lung cancer bone metastasis. Among them, FADS1 appeared to have a regulatory role, influencing downstream targets. Notably, CLCF1 and COQ10A showed significantly increased expression in FADS1-knockdown cells, consistent with the network's predictions. These findings suggest that Bayesian network analysis is a reliable machine learning approach for uncovering causal gene relationships in cancer metastasis. Furthermore, FADS1 may serve as a potential therapeutic target in lung cancer bone metastasis. The validity of this network was supported by in vitro experiments using a lung cancer cell line. Show less

📄 PDF DOI: 10.11005/jbm.25.863

Genomics-informed drug-repurposing strategy identifies two therapeutic targets for preventing liver disease associated with metabolic dysfunction.

Hannah M Seagle, Alexis T Akerele, Joseph A DeCorte +20 more · 2025 · American journal of human genetics · Elsevier · added 2026-04-24

Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving the treatment of diseases. We employed a cross-discipl Show more

Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving the treatment of diseases. We employed a cross-disciplinary approach to identify potential therapeutics for the prevention of metabolic-dysfunction-associated steatotic liver disease (MASLD) in at-risk individuals by using humans as a model organism. We identified 212 putative candidate genes associated with MASLD by using data from a large multi-ancestry genetic association study, of which 158 (74.5%) were previously unreported. From this set, we identified 57 genes that encode for druggable protein targets and for which the effects of increasing genetically predicted gene expression on MASLD risk align with the function of that drug on the protein target. We then used We then evaluated these potential targets for evidence of efficacy by using Mendelian randomization, pathway analysis, and protein structural modeling. Through these approaches, we present compelling evidence to suggest that the activation of FADS1 by icosapent ethyl, as well as S1PR2 by fingolimod, could be a promising therapeutic strategy for MASLD prevention. Show less

📄 PDF DOI: 10.1016/j.ajhg.2025.06.014

Genomics-Informed Drug Repurposing Strategy Identifies Novel Therapeutic Targets for Metabolic Dysfunction-Associated Steatotic Liver Disease.

Hannah M Seagle, Alexis T Akerele, Joseph A DeCorte +19 more · 2025 · medRxiv : the preprint server for health sciences · Cold Spring Harbor Laboratory · added 2026-04-24

Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving treatment of diseases. We employed a cross-disciplinar Show more

Identification of drug-repurposing targets with genetic and biological support is an economically and temporally efficient strategy for improving treatment of diseases. We employed a cross-disciplinary approach to identify potential treatments for metabolic dysfunction associated steatotic liver disease (MASLD) using humans as a model organism. We identified 212 putative causal genes associated with MASLD using data from a large multi-ancestry genetic association study, of which 158 (74.5%) are novel. From this set we identified 57 genes that encode for druggable protein targets, and where the effects of increasing genetically predicted gene expression on MASLD risk align with the function of that drug on the protein target. These potential targets were then evaluated for evidence of efficacy using Mendelian randomization, pathway analysis, and protein structural modeling. Using these approaches, we present compelling evidence to suggest activation of Show less

📄 PDF DOI: 10.1101/2025.02.18.25321035

Causal association between polyunsaturated fatty acids and acne: a two-sample Mendelian randomization study.

Bo Ri Kim, Gahyun Kim, Seon-Pil Jin +3 more · 2025 · The British journal of dermatology · Oxford University Press · added 2026-04-24

Bo Ri Kim, Gahyun Kim, Seon-Pil Jin, Chong Won Choi, Jinho Kim, Hyunsun Park Show less

Observational studies have demonstrated a close association between polyunsaturated fatty acids (PUFAs) and acne. However, the findings of clinical trials have been inconsistent, leaving the causal re Show more

Observational studies have demonstrated a close association between polyunsaturated fatty acids (PUFAs) and acne. However, the findings of clinical trials have been inconsistent, leaving the causal relationship between PUFAs and acne unclear. To investigate the causal association between genetically proxied PUFAs and acne risk. Mendelian randomization (MR) was performed using single nucleotide polymorphisms associated with PUFAs as instrumental variables. The causal associations between PUFAs and acne were estimated among 115 006 UK Biobank participants and 363 927 participants of Finnish descent. Genetically predicted docosahexaenoic acid (DHA) levels [β = -0.303, 95% confidence interval (CI) -0.480 to -0.126; P = 7.74 × 10-4] and its percentage to total fatty acids (β = -0.402, 95% CI -0.651 to -0.258; P = 5.91 × 10-6) showed a significant causal association with a decreased risk of acne. Conversely, genetically predicted percentages of linoleic acid (LA) in total fatty acids (β = 0.768, 95% CI 0.411-0.126; P = 2.87 × 10-4) and omega-6 : omega-3 ratio (β = 0.373, 95% CI 0.142-0.604; P = 4.48 × 10-3) were robustly associated with an increased risk of acne. These effects were attenuated after excluding a genetic variant of rs174528 located upstream of FADS1, highlighting the biologic link between FADS1 and delta-5 desaturase activity. Multivariable MR analysis indicated that PUFAs were causally associated with acne, independent of body mass index. Our study indicates that high DHA levels and their ratios to total fatty acids have causal protective effects against acne, while high LA levels and omega-6 : omega-3 ratio are associated with increased acne risk. This association was largely attributable to the influence of genetic variants related to FADS1. Show less

no PDF DOI: 10.1093/bjd/ljaf052

A Multikinase Inhibitor AX-0085 Blocks FGFR1 Activation to Overcomes Osimertinib Resistance in Non-Small Cell Lung Cancer.

Byung-Ho Rhie, Janardhan Keshav Karapurkar, Hyun-Yi Kim +10 more · 2025 · Biomedicines · MDPI · added 2026-04-24

Byung-Ho Rhie, Janardhan Keshav Karapurkar, Hyun-Yi Kim, Sang Hyeon Woo, D A Ayush Gowda, Dong Ha Kim, Myeong Jun Choi, Young Jun Park, Viswanathaiah Matam, Yoonki Hong, Seok-Ho Hong, Suresh Ramakrishna, Kye-Seong Kim Show less

📄 PDF DOI: 10.3390/biomedicines14010066

Design, Synthesis, and Biological Evaluation of 5',7-Disubstituted 7-Deaza-adenosine Analogues as Irreversible Pan-FGFR Inhibitors.

Jung Hoon Park, Phuong Thao Tran, Hye Lin Ko +13 more · 2025 · Pharmaceuticals (Basel, Switzerland) · MDPI · added 2026-04-24

Jung Hoon Park, Phuong Thao Tran, Hye Lin Ko, Seonghee Mun, Sung Chul Jang, Dong Hyun Moon, Jaeho Han, Jieun Kim, Gibae Kim, Hongseok Choi, Seung Woo Kim, Minjae Kim, Sang Kook Lee, Byung Woo Han, Keon Wook Kang, Lak Shin Jeong Show less

📄 PDF DOI: 10.3390/ph18111745

8-Hydroxy-2-Anilino-1,4-Naphthoquinone Prevents Against Ferroptotic Neuronal Death and Kainate-Induced Epileptic Seizures.

Daseul Lee, Eun Jung Na, Yumi Heo +2 more · 2025 · Pharmaceutics · MDPI · added 2026-04-24

Daseul Lee, Eun Jung Na, Yumi Heo, Jinha Yu, Hwa-Jung Kim Show less

📄 PDF DOI: 10.3390/pharmaceutics17111415

Oral microbial signatures underlying recurrence via PI3K/AKT/mTOR pathway modulation in oral squamous cell carcinoma.

Da-Woon Kwack, Zeba Praveen, Yeon-Hee Kim +7 more · 2025 · Journal of oral microbiology · Taylor & Francis · added 2026-04-24

Da-Woon Kwack, Zeba Praveen, Yeon-Hee Kim, Chong Woo Yoo, Jae Hee Ko, Suk Min Youn, Joo Yong Park, Jong-Ho Lee, Sung Weon Choi, Mi Kyung Kim Show less

Oral squamous cell carcinoma (OSCC) often recurs locally, reducing survival. The oral microbiome may influence tumor recurrence, but its prognostic role is unclear. This study investigated oral microb Show more

Oral squamous cell carcinoma (OSCC) often recurs locally, reducing survival. The oral microbiome may influence tumor recurrence, but its prognostic role is unclear. This study investigated oral microbiomes associated with OSCC recurrence and their prognostic merit. Saliva samples were collected from 133 patients with OSCC. 16S rRNA gene sequencing was performed, and microbial signatures were predicted via XGBoost. Functional metagenomic prediction was conducted using PICRUSt2. XGBoost identified Oral saliva microbiome profiling reveals distinct microbial patterns associated with OSCC recurrence. Our correlation-based functional predictions indicated that the enrichment of Show less

📄 PDF DOI: 10.1080/20002297.2025.2560020

Caffeic acid phenethyl ester disrupts germ layer specification in Xenopus embryos.

Gang-Ho Yoon, Myeoung Su Kim, Sun-Cheol Choi · 2025 · Reproductive toxicology (Elmsford, N.Y.) · Elsevier · added 2026-04-24

Xenopus embryo serves as an ideal model for teratogenesis assays to observe the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our sc Show more

Xenopus embryo serves as an ideal model for teratogenesis assays to observe the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening of a chemical library with frog embryo, caffeic acid phenethyl ester (CAPE) was found to upregulate the FGF/MAPK pathway, disrupting germ layer formation in early development. Exposure to CAPE interfered with the formation of anterior-posterior body axis and of ectodermal derivatives such as eyes, dorsal fin and pigment cells. These inhibitory effects were achieved by promoting paraxial mesodermal specification and neural differentiation concomitant with a repression of epidermal and neural crest cell fates. This compound also induced the caudalization of anterior neural fate, thereby recapitulating the activity of the FGF/MAPK signals in the anterior-posterior patterning of neural tissue. Consistently, phosphorylation of extracellular signal-regulated kinase (ERK) was elevated in CAPE-treated cells, which was mediated by the FGFR1 and FGFR4 pathway. Together, these results suggest that CAPE functions as an activator of the FGF/MAPK signaling pathway, generating severe teratogenic effects on germ layer specification in vertebrate early development. Show less

no PDF DOI: 10.1016/j.reprotox.2025.109046

Dysregulation of FGFR1 signaling in the hippocampus facilitates depressive disorder.

Jongpil Shin, Hyeonsik Oh, Ji Hye Park +5 more · 2025 · Experimental & molecular medicine · Nature · added 2026-04-24

Jongpil Shin, Hyeonsik Oh, Ji Hye Park, Hyunsik Bae, Chan Mo Yang, Minju Lee, Seokhwi Kim, Won Do Heo Show less

Major depressive disorder (MDD) is a complex psychological disorder with a sophisticated molecular etiology. Although its connection with fibroblast growth factor receptor 1 (FGFR1) in the hippocampus Show more

Major depressive disorder (MDD) is a complex psychological disorder with a sophisticated molecular etiology. Although its connection with fibroblast growth factor receptor 1 (FGFR1) in the hippocampus is known, the precise mechanisms underlying its pathophysiology remain unclear. Here we conduct a comprehensive analysis of the molecular profile of the hippocampus in patients with MDD. We identified a distinct overexpression of FGFR1 specifically within the dentate gyrus of patients with MDD. Through the use of optogenetic techniques for the in vivo spatiotemporal dissection of FGFR1 signaling, we uncovered a sequential FGFR1-Notch-brain-derived neurotrophic factor (BDNF) pathway within the dentate gyrus, which can ultimately induce adult hippocampal neurogenesis, significantly contributing to antidepressant effects. We discovered that the dysregulation of this axis by the protein Numb, which demonstrates an age-related increase in individuals with MDD, is closely associated with the development of depressive phenotypes. Remarkably, targeting Numb to restore this axis effectively reversed the depressive phenotype, thus offering new insights into potential therapeutic strategies. Show less

📄 PDF DOI: 10.1038/s12276-025-01519-9

Analysis of sex-differential gene expression on the target of approved drug.

Yunha Suh, Jun-Gyu Lee, Kwang-Eun Kim · 2025 · Scientific reports · Nature · added 2026-04-24

Sex is a key piece of patient information but is often not actively considered in drug use. This is partly due to the lack of molecular evidence at the gene expression level beyond sex chromosomes and Show more

Sex is a key piece of patient information but is often not actively considered in drug use. This is partly due to the lack of molecular evidence at the gene expression level beyond sex chromosomes and sex hormones. We aim to investigate how sex differences in tissue-specific gene expression relate to FDA-approved drugs using the latest database of The Genotype-Tissue Expression (GTEx) V10. Our analysis reveals that 91.4% of FDA-approved drug target genes exhibit sex-differential expression in at least one tissue. The tissues with the most pronounced sex differences include subcutaneous adipose tissue, skeletal muscle, and the pituitary gland, while sex differences are less pronounced in the liver, other brain regions, and the spleen. Sex-differential disease-related genes include those associated with obesity (PPARG, INSR), cancer (FGFR1, CD22), and immunity (IL6R, IL3RA). Based on our findings, we advocate for a policy shift that integrates sex-based molecular data into preclinical studies, drug development, and clinical practices. This paradigm aligns biomedical research with precision medicine, mitigates drug-related risks, and promotes equitable healthcare outcomes. Show less

📄 PDF DOI: 10.1038/s41598-025-12342-7

Discovery of INCB126503 as a Potent and Selective FGFR2/3 Inhibitor.

Minh H Nguyen, Anlai Wang, Lisa Truong +23 more · 2025 · ACS medicinal chemistry letters · ACS Publications · added 2026-04-24

Fibroblast growth factor receptors (FGFRs) are well-established oncology targets, with aberrant FGFR2 and FGFR3 activation implicated in multiple tumor types, including cholangiocarcinoma and urotheli Show more

Fibroblast growth factor receptors (FGFRs) are well-established oncology targets, with aberrant FGFR2 and FGFR3 activation implicated in multiple tumor types, including cholangiocarcinoma and urothelial carcinoma. Currently approved FGFR2/3-targeted therapies rely on pan-FGFR small-molecule kinase inhibitors, which often lead to off-target toxicities due to unintended inhibition of FGFR1 and FGFR4, as well as acquired resistance driven by gatekeeper mutations. Herein, we report the discovery of INCB126503, a highly potent, orally bioavailable FGFR2/3 inhibitor with excellent isoform selectivity and equipotent activity against gatekeeper mutants. INCB126503 effectively suppresses FGFR signaling in vivo without inducing hyperphosphatemia and demonstrates significant antitumor efficacy in xenograft models harboring FGFR3 genetic alterations. Show less

no PDF DOI: 10.1021/acsmedchemlett.5c00232

High Dietary Phosphate Intake Induces Hypertension and Sympathetic Overactivation via Central Fibroblast Growth Factor Receptor Signaling.

Han-Kyul Kim, Ayumi Fukazawa, Scott A Smith +9 more · 2025 · Circulation · added 2026-04-24

Han-Kyul Kim, Ayumi Fukazawa, Scott A Smith, Masaki Mizuno, Beverly A Rothermel, Teppei Fujikawa, Marco Galvan, Laurent Gautron, Johanne V Pastor, Isabelle J Carroll, Orson W Moe, Wanpen Vongpatanasin Show less

Recent studies have highlighted the deleterious role of high phosphate intake in hypertension via sympathetic overactivation, yet the underlying mechanisms remain unclear. Dietary phosphate loading tr Show more

Recent studies have highlighted the deleterious role of high phosphate intake in hypertension via sympathetic overactivation, yet the underlying mechanisms remain unclear. Dietary phosphate loading triggers physiologic release of FGF23 (fibroblast growth factor-23) from the bone to maintain phosphate homeostasis. Both FGF23 and FGF receptors (FGFRs) are present in the central nervous system, but their role in neural control of blood pressure during phosphate loading is unknown. We investigated central FGF23/FGFR signaling in high-phosphate diet-induced sympathetic dysregulation of blood pressure in rats. FGF23 protein levels were measured by immunoprecipitation, immunoblotting, and immunohistochemistry. FGF23 translocation into the brain was determined by injecting infrared-labeled FGF23 intravenously into anesthetized Sprague-Dawley rats. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to hindlimb muscle contraction were measured in decerebrate Sprague-Dawley rats treated with either a normal 0.6% phosphate diet (NP) or a high 1.2% phosphate diet (HP) for 12 weeks before and after intracerebroventricular (ICV) administration of FGFR signaling inhibitors. Excess phosphate intake significantly increased FGF23 protein levels in the brainstem (HP versus NP, Our data reveal a novel pathophysiologic paradigm of high-phosphate diet-induced sympathoexcitation and hypertension by FGF23 crossing into the brain, possibly acting via FGFR4. Show less

no PDF DOI: 10.1161/CIRCULATIONAHA.124.071605

SH003 Inhibits Proliferation and Induces Apoptosis in NSCLC Cell Lines by Inhibiting the Receptor Tyrosine Kinase-related Pathway.

Hyun-Ha Hwang, Ji-Sung Yoo, Jeong-Hui Je +7 more · 2025 · Anticancer research · added 2026-04-24

Hyun-Ha Hwang, Ji-Sung Yoo, Jeong-Hui Je, Hyeong-Chan Lee, Tae Hun Kim, Yun-Beom Sim, Kwang-Jin Cho, Taehyoun Kim, Sung-Gook Cho, Seong-Gyu Ko Show less

SH003, a novel herbal mixture consisting of NSCLC cell lines (A549, H460, HCC827) were treated with SH003 to evaluate cell viability (MTT assay), colony formation, apoptosis (Annexin V/7-AAD staining, Show more

SH003, a novel herbal mixture consisting of NSCLC cell lines (A549, H460, HCC827) were treated with SH003 to evaluate cell viability (MTT assay), colony formation, apoptosis (Annexin V/7-AAD staining, western blot), and cell cycle distribution (PI staining). Phosphorylation of RTKs and related signaling molecules was analyzed using a phospho-RTK array and western blot. NSCLC cell lines A549, H460, and HCC827 treated with SH003 showed significant, dose-dependent cell viability and colony formation reductions. SH003 induced apoptosis, evidenced by increased cleaved PARP and caspase-8 levels, and caused G SH003 is a promising multi-target therapeutic agent for NSCLC, offering a novel strategy to improve patient outcomes. Show less

no PDF DOI: 10.21873/anticanres.17574

Perillic acid disrupts the specification of germ layers by upregulating the FGF/MAPK pathway.

Gang-Ho Yoon, Dong-Seok Park, Myeoung Su Kim +1 more · 2025 · Genes & genomics · Springer · added 2026-04-24

Gang-Ho Yoon, Dong-Seok Park, Myeoung Su Kim, Sun-Cheol Choi Show less

Xenopus embryo is an ideal model for teratogenesis assays to assess the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening Show more

Xenopus embryo is an ideal model for teratogenesis assays to assess the effects of any compounds on the cellular processes crucial for early development and adult tissue homeostasis. In our screening of a chemical library with frog embryo to identify novel compounds that exert specific effects on key cellular signaling pathways, perillic acid (PA) was found to disrupt germ layer specification in early development. Thus, the mechanism underlying this effect was investigated. Embryos were exposed to PA during a specific period of early development to observe stage-specific morphological alterations induced by this compound. Whole-mount in situ hybridization was performed to examine its effects on ectodermal and mesodermal differentiation and the anterior-posterior patterning of neural tissue. Western blotting analysis was employed to identify the signaling pathways through which PA influences germ layer formation in Xenopus development. PA-treated embryos exhibited the shortening of the anterior-posterior body axis, truncation of craniofacial structures and malformation of neural crest (NC). These severe morphological defects occurred when embryos became exposed to PA during the gastrula stages. Consistent with these phenotypes, treatment with PA caused significant expansion of neural tissue concomitant with a reduction of epidermal and NC cell fates. Furthermore, PA induced the caudalization of neural fate and expressions of paraxial mesodermal genes, recapitulating the activity of the FGF/MAPK signals in germ layer specification. In line with this, ERK activation could be induced by PA treatment, which was mediated by the FGFR1 pathway. PA affects the anterior-posterior neural patterning and mesodermal specification by activating the FGF/MAPK signaling pathway. Show less

📄 PDF DOI: 10.1007/s13258-025-01641-y

Effects of FGF-related gene polymorphisms on cerebral infarction in patients treated with direct oral anticoagulants.

Jung Sun Kim, Minju Park, Yoon-A Park +8 more · 2025 · Vascular pharmacology · Elsevier · added 2026-04-24

Jung Sun Kim, Minju Park, Yoon-A Park, Da Hoon Lee, Seo-A Choi, Eun Jeong Jang, Jeong Yee, Dong-Hyeok Kim, Tae-Jin Song, Junbeom Park, Hye Sun Gwak Show less

The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene poly Show more

The development of cerebral infarction is multifactorial, including both environmental and genetic factors. This study assessed the association between fibroblast growth factor (FGF)-related gene polymorphisms and the incidence of cerebral infarction among patients on direct oral anticoagulants (DOACs). Patients over 18 years old with atrial fibrillation who were receiving DOACs for cerebral infarction prevention at Ewha Womans University Mokdong Hospital and Ewha Womans University Seoul Hospital were enrolled in this analysis. Twenty-one single nucleotide polymorphisms (SNPs) from FGF1, FGF2, and FGFR1 were examined. In multivariable logistic regression analysis, three models (Model I: demographic factors only, Model II: demographic factors and genetic factors, and Model III: genetic factors and the CHA Among the 536 candidate patients, 21 (3.9 %) experienced cerebral infarction while taking DOACs. From Model I and Model II, age ≥ 75 years and previous thromboembolic event history increased the risk of cerebral infarction. For genetic factors in Model II and III, FGF1 rs1596776 GG, FGFR1 rs6996321 AA, and FGFR1 rs7012413 TT genotypes were associated with a higher risk of cerebral infarction. The area under the receiver operating curve increased from 0.747 (Model I) to 0.822 (Model II) by adding genetic factors, demonstrating better model performance. This study uncovered the association between FGF-related gene polymorphisms and cerebral infarction among patients with atrial fibrillation undergoing DOAC therapy. Show less

no PDF DOI: 10.1016/j.vph.2025.107466