Yu Ha Shim, Yu Jin Kim, Ji Soo Ryu, Jin Young An, Seung A Oh, Byeong Jun Mun, Jeong Hyang Park, Hye Ri Kim, Soon Ha Kim, Zhongwei Huang, Jae Ho Lee
{"title":"MIT-001 ameliorates ferroptosis-induced mitochondrial dysfunction and enhances embryo quality in preimplantation embryos from aged female mice.","authors":"Yu Ha Shim, Yu Jin Kim, Ji Soo Ryu, Jin Young An, Seung A Oh, Byeong Jun Mun, Jeong Hyang Park, Hye Ri Kim, Soon Ha Kim, Zhongwei Huang, Jae Ho Lee","doi":"10.1016/j.biopha.2025.118393","DOIUrl":"10.1016/j.biopha.2025.118393","url":null,"abstract":"<p><p>Advanced maternal age is closely associated with reduced oocyte and embryo quality, impaired mitochondrial function, and decreased implantation potential. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a key contributor to the age-related decline in reproductive capacity. In this study, we investigated the therapeutic potential of mitochondria-targeted 001 (MIT-001), a novel anti-ferroptosis agent, to improve the quality of preimplantation embryos derived from aged female mice. In vitro assays using human granulosa-like KGN cells demonstrated that MIT-001 effectively protected against Ras-selective lethal 3 (RSL3)-induced ferroptosis, restored cell viability, and recovered estradiol synthesis, indicating that steroidogenic function was restored. To evaluate the efficacy of MIT-001 in vitro, preimplantation embryos were collected from aged BDF1 mice and cultured in the presence of MIT-001. Embryos treated with MIT-001 showed significantly improved developmental progression and increased blastocyst formation rates compared with untreated controls. Furthermore, MIT-001 enhanced the mitochondrial membrane potential and oxygen consumption rate, as assessed by live confocal imaging and Seahorse assays, suggesting that mitochondrial function was restored. These findings highlight the role of ferroptosis in deterioration of embryo quality associated with maternal aging and demonstrate that MIT-001 mitigates ferroptosis-induced cellular damage. In conclusion, MIT-001 is a promising candidate for therapeutic intervention to improve clinical reproductive outcomes in aged females by targeting mitochondrial dysfunction and regulated cell death pathways.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118393"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harshal A Shah, Hasan Slika, Fnu Ruchika, Danielle Golub, Michael Schulder, Henry Brem, Amir Manbachi, Jordina Rincon-Torroella, Chetan Bettegowda, Pavlos Anastasiadis, Francesco Prada, Graeme F Woodworth, Betty M Tyler
{"title":"Mechanistic insights and basis for real-time monitoring and closed-loop feedback control in sonodynamic therapy for glioblastoma.","authors":"Harshal A Shah, Hasan Slika, Fnu Ruchika, Danielle Golub, Michael Schulder, Henry Brem, Amir Manbachi, Jordina Rincon-Torroella, Chetan Bettegowda, Pavlos Anastasiadis, Francesco Prada, Graeme F Woodworth, Betty M Tyler","doi":"10.1016/j.biopha.2025.118433","DOIUrl":"10.1016/j.biopha.2025.118433","url":null,"abstract":"<p><p>Sonodynamic therapy (SDT) involves the administration of otherwise inactive agents that can be activated by acoustic energy ('sonosensitizers') to impart therapeutic effects. SDT is a treatment of significant clinical interest in glioblastoma, a highly aggressive brain tumor, due to the known uptake and conversion of the clinically approved fluorescence guided surgery agent, 5-aminolevulinic acid (5-ALA). Building evidence suggests acoustic energy may activate the converted product of 5-ALA, protoporphyrin IX. Despite ongoing clinical trials using 5-ALA-based SDT demonstrating treatment safety, feasibility, and potential efficacy, the precise underlying tumoricidal mechanisms of SDT remain unknown. Additionally, the ability to monitor SDT effects during treatments remains underexplored. Here we synthesize existing evidence regarding mechanisms behind the antitumoral effects of SDT, including various SDT agents studied in their capacity to generate reactive oxygen species that result in intrinsic apoptotic pathway activation, sonomechanical effects that result in cellular damage, pyrolytic and sonoluminescent reactions, and immunological activation. Additionally, we discuss the opportunities for in situ, real-time monitoring of SDT and related effects to enable safe, reproducible, and prescriptive treatments. Specifically, we explore the potential utility of magnetic resonance (MR) based monitoring tools including MR thermometry and MR acoustic radiation force imaging, and acoustic emissions feedback monitoring.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118433"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep learning model enables the discovery of a novel BET inhibitor YD-851.","authors":"Hongyin Sun, Guoli Xiong, Xin Li, Jian Sun, Chunlan Hu, Zhangxiang Zhao, Chao Lv, Wei Su, Lifeng Li, Jie Zhao, Zhenliang Sun, Dongsheng Cao, Mingzhu Yin","doi":"10.1016/j.biopha.2025.118431","DOIUrl":"10.1016/j.biopha.2025.118431","url":null,"abstract":"<p><p>BET inhibitor is a novel strategy in tumor therapy based on targeting epigenetic mechanism. In recent decades, dozens of clinical trials have been conducted to validate the potential efficacy of the first-generation BET inhibitors in refractory cancer and non-cancerous ailments. However, limited efficacy and significant toxicity were observed in clinical trials for treating solid tumors. Here, we proposed a novel inhibitor strategy as well as an effective and low toxicity agent that can effectively kill tumor cells and exhibited low toxicity. A ring-closure scaffold hopping approach and high-precision deep learning models was leveraged to furnish a series of rationally designed carboline derivatives as desired BET inhibitors. These most potent compounds were synthesized by an efficient and facile multistep route. Subsequent evaluations identified a potent BET inhibitor YD-851 and it can effectively inhibit tumor cell proliferation. In addition, YD-851 causes tumor shrinkage and significantly suppresses tumor growth in multiple xenograft solid tumor models. Moreover the results of toxicity texting and pharmacokinetic properties support further development of YD-851. We obtain an effective and low toxicity preclinical candidate for BET inhibitor to treat solid tumors. And the success of our strategy encourages the implementation of similar methods in the drug discovery of other targets.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118431"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Visual cycle and LC3-associated phagocytosis in retina: regulatory mechanisms and therapeutic potential.","authors":"Fanfei Liu, Qiqi Li, Yang Yang, Fang Lu","doi":"10.1016/j.biopha.2025.118423","DOIUrl":"10.1016/j.biopha.2025.118423","url":null,"abstract":"<p><p>The visual cycle plays a pivotal dual role in retina, while it's essential for maintaining vision through continuous regeneration of the light-sensitive 11-cis-retinal chromophore. Its dysregulation contributes significantly to retinal degenerative disorders including age-related macular degeneration (AMD) and Stargardt disease. Recent advances have elucidated multiple therapeutic targets in visual cycle, ranging from inhibition of enzymatic activity of RPE65 and lecithin retinol acyltransferase (LRAT) to modulation of retinoid transport proteins and enhancement of protective LC3-associated phagocytosis. Pharmacological interventions of the visual cycle demonstrate promising results in reducing toxic retinoid accumulation, though clinical application faces challenges including nyctalopia, delayed dark adaptation, and dyschromatopsia. Future research directions emphasize the need for targeted visual cycle modulators that can selectively disrupt pathological processes without compromising essential visual function. This review summarizes the visual cycle and LC3-associated phagocytosis associated with various retinal diseases, highlights recent advances in pharmacological modulation of visual cycle, and aims to provide new insights into therapeutic strategies for retinal degenerative disorders.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118423"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radziejewska, K Czerwińska, B Popławska, A Galicka
{"title":"Rosmarinic acid influences the expression of glycoforms in DLD-1 and HT-29 colon cancer cells.","authors":"Radziejewska, K Czerwińska, B Popławska, A Galicka","doi":"10.1016/j.biopha.2025.118432","DOIUrl":"10.1016/j.biopha.2025.118432","url":null,"abstract":"<p><p>Rosmarinic acid (RA) is polyphenolic compound with beneficial, health-promoting effects. Specifically altered glycosylation of cancer cells is strongly related to cancer progress and poor prognosis. Due to limited studies regarding the influence of RA on this process in colon tumor cells, we examined how this acid at concentrations 200 and 400 μM influences selected glycoforms, enzymes taking part in their forming as well as Gal-3 and Akt, in DLD-1 and HT-29 colon cancer cells. To determine the expression of studied factors, RT-qPCR, ELISA and Western blotting were applied. We revealed inhibitory effect of RA in both cell lines on MUC1, ppGalNAcT2, C1GalT1, Cosmc, ST3GalT1, FUT3/4, Gal-3, and Akt mRNAs. ST6GalNAcT1 mRNA was suppressed by both RA concentrations in DLD-1 and by 400 μM RA in HT-29 cell line. In HT-29 cells, both RA concentrations inhibited all examined sugar antigens released to the culture medium and T, sialyl T, and fucosylated epitopes measured in cell lysates. Tn and sialyl Tn antigens in cell lysates were suppressed only by 400 μM RA. In DLD-1 cells, both RA concentrations inhibited sialyl Tn, T antigens in medium and sialyl T in cell lysates. T epitope in lysates was inhibited only by 400 μM RA. Moreover, both RA concentrations suppressed C1GalT1, Gal-3 and pAkt proteins in DLD-1 cells. In HT-29 cells, both RA concentrations suppressed MUC1 extracellular domain; C1GalT1 was diminished by 200 μM RA, Gal-3 and pAkt by 400 μM RA. The data suggest possible benefit of RA as the agent supporting colon cancer treatment.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118432"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ST1-YtnP lactonase from extreme environment: A promising antivirulence agent against multidrug-resistant Pseudomonas aeruginosa.","authors":"Jovana Curcic, Ivano Merendino, Danka Matijasevic, Branko Jovcic, Silvia Spriano, Milka Malesevic","doi":"10.1016/j.biopha.2025.118443","DOIUrl":"10.1016/j.biopha.2025.118443","url":null,"abstract":"<p><p>The emergence of multidrug-resistant (MDR) pathogens, particularly Pseudomonas aeruginosa, requires innovative therapeutic strategies. This study investigates the potential of ST1-YtnP lactonase, an enzyme isolated from the thermophilic bacterium Bacillus licheniformis, which is found in the extreme environment of the Vranjska Banja hot springs. The extreme conditions in this habitat offer untapped potential for the discovery of biotechnologically valuable, resilient enzymes. ST1-YtnP lactonase was shown to effectively degrade acyl-homoserine lactones (AHLs), thereby disrupting the quorum sensing (QS) system of P. aeruginosa and reducing its virulence. ST1-YtnP significantly reduced biofilm formation without inhibiting bacterial growth Furthermore, in vitro analysis revealed that ST1-YtnP lactonase exhibited a synergistic effect with gentamicin and an additive effect with meropenem, enhancing the efficacy of these antibiotics against P. aeruginosa MMA83. In vivo, the combination of meropenem and ST1-YtnP lactonase completely rescued Caenorhabditis elegans from infection, surpassing the protective effect of meropenem alone. ST1-YtnP lactonase showed no adverse effects on the survival of uninfected nematodes, while it significantly enhanced the survival of P. aeruginosa-infected nematodes treated with the enzyme. These findings emphasize the potential of ST1-YtnP lactonase as a novel antivirulence agent with promising biotechnological applications to combat antibiotic-resistant infections.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"190 ","pages":"118443"},"PeriodicalIF":7.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}