Biomedicine & Pharmacotherapy最新文献

{"title":"Partial versus whole tumor-volume irradiation in combination with immunotherapy: Comparable outcomes in immunosuppressed mouse models of oral squamous cell carcinoma","authors":"Ziva Pisljar ,&nbsp;Bostjan Markelc ,&nbsp;Simona Kranjc Brezar ,&nbsp;Tim Bozic ,&nbsp;Gregor Sersa ,&nbsp;Maja Cemazar ,&nbsp;Tanja Jesenko","doi":"10.1016/j.biopha.2025.118107","DOIUrl":"10.1016/j.biopha.2025.118107","url":null,"abstract":"<div><div>Radiotherapy is a standard therapy for oral squamous cell carcinoma (OSCC) with immunomodulatory potential. Due to high lymphocyte radiosensitivity, partial tumor-volume irradiation (pIR), targeting only part of the tumor, is being explored for immunomodulation. This study compared the effects of whole tumor-volume irradiation (IR) and pIR, targeting approximately 50 % of the tumor volume, in combination with anti-PD-1 immune checkpoint inhibitors (ICI). The therapeutic efficacy of a single 15 Gy IR or pIR dose combined with anti-PD-1 ICI was evaluated in two immune cold murine OSCC models: human papillomavirus (HPV)-negative MOC1 and HPV-positive MOC1-HPV K1 stably expressing HPV-16 oncogenes E6/E7. Additionally, immune cell populations in the tumor microenvironment (TME) were analyzed using flow cytometry. Both IR and pIR induced transient immune cell infiltration in the TME. However, pIR led to significantly lower tumor growth inhibition than IR. While IR + ICI failed to improve survival compared to IR alone, pIR + ICI significantly prolonged survival compared to pIR alone in the MOC1 model, along with increase in cytotoxic T cell infiltration. In the MOC1-HPV K1 model, responses varied. Responding tumors were enriched with effector memory T cells, whereas non-responders exhibited increased neutrophil (MDSCs) and monocyte-derived dendritic cells infiltration. The study indicates that while pIR has immunomodulatory potential, its effects are comparable to IR in the tested settings. Further research is needed to optimize dosing and scheduling for pIR and anti-PD-1 ICI. Additionally, combination with other immunotherapies could be explored in further studies to enhance treatment efficacy in immune cold OSCC models.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118107"},"PeriodicalIF":6.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ru(II)-thymine complex suppresses acute myeloid leukemia stem cells by inhibiting NF-κB signaling","authors":"Maiara de S. Oliveira ,&nbsp;Ingrid R.S.B. Dias ,&nbsp;Rafaela G.A. Costa ,&nbsp;Ana Carolina B. da C. Rodrigues ,&nbsp;Suellen L.R. Silva ,&nbsp;Milena B.P. Soares ,&nbsp;Rosane B. Dias ,&nbsp;Ludmila F. Valverde ,&nbsp;Clarissa A. Gurgel Rocha ,&nbsp;Alzir A. Batista ,&nbsp;Rodrigo S. Correa ,&nbsp;Valdenizia R. Silva ,&nbsp;Eugênia T. Granado Pina ,&nbsp;Daniel P. Bezerra","doi":"10.1016/j.biopha.2025.118080","DOIUrl":"10.1016/j.biopha.2025.118080","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a lethal hematologic malignancy caused by leukemic blasts that fail to mature normally. AML has a high relapse rate, primarily due to a small subset known as leukemic stem cells (LSCs). In this work, we investigated the ability of a Ru(II)-thymine complex (RTC) with the formula [Ru(PPh₃)₂(Thy)(bipy)]PF₆ (where PPh₃ = triphenylphosphine, Thy = thymine, and bipy = 2,2′-bipyridine) to suppress AML LSCs. RTC exhibited potent cytotoxicity toward both solid and hematologic malignancies and suppressed primary AML LSCs, as observed by the reduction in the CD34 +CD38- cell population. In the AML cell line KG-1a, which has an LSC-like population, RTC reduced the number of CD34 + and CD123 + cells. A reduction in leukemic blasts was detected in the bone marrow of RTC-treated NSG mice bearing KG-1a xenografts. Increased DNA fragmentation, YO-PRO-1 staining, active caspase-3 and cleaved PARP (Asp 214) levels, and mitochondrial superoxide levels were detected in RTC-treated KG-1a cells. The pancaspase inhibitor Z-VAD-(OMe)-FMK, but not the antioxidant <em>N</em>-acetylcysteine, partially prevented RTC-induced cell death in KG-1a cells, indicating that RTC induces caspase-mediated apoptosis in KG-1a cells via an oxidative stress-independent pathway. In molecular mechanism studies, transcripts of the NF-κB inhibitor <em>NFKBIA</em> were upregulated, and the level of NF-κB p65 phosphorylated at the Ser529 residue was reduced in RTC-treated KG-1a cells, indicating that RTC may inhibit NF-κB signaling. Overall, these results indicate the anti-AML potential of RTC in AML LSCs via the suppression of NF-κB signaling.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118080"},"PeriodicalIF":6.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Au@Fe₃O₄@PEG nanocubes as photoactive agents in photothermal therapy: An in vitro study","authors":"Aleksandra Wolińska ,&nbsp;Marcin Drozd ,&nbsp;Barbara Buchalska ,&nbsp;Artur Dybko ,&nbsp;Ilona Grabowska-Jadach","doi":"10.1016/j.biopha.2025.118051","DOIUrl":"10.1016/j.biopha.2025.118051","url":null,"abstract":"<div><div>Photothermal therapy (PTT) is an emerging cancer treatment that utilizes near-infrared (NIR) light and photoactive agents to induce localized hyperthermia, leading to cancer cell destruction. Magnetic nanoparticles (MNPs) with plasmonic properties, such as Fe₃O₄@Au hybrids, hold great potential for PTT due to their combined magnetic and optical functionalities. This study investigates the potential of Fe₃O₄@Au@PEG-OH and Fe₃O₄@Au@PEG-NH₂ core-shell nanoparticles as photoactive agents for PTT applications. The nanoparticles were synthesized and characterized for their physicochemical properties, including zeta potential and absorption spectra. Their ability to convert electromagnetic radiation into thermal energy was assessed, and their cytotoxicity was evaluated in normal and cancer cell lines (A549, MRC-5, A375, HaCaT). The effectiveness of PTT was tested at a nanoparticle concentration of 75 μg/mL under NIR laser irradiation. The results demonstrated strong NIR absorption and efficient photothermal conversion, with cytotoxicity tests confirming low toxicity in most cases. PTT treatment significantly reduced cancer cell viability, with up to a 7 % decrease in cell viability, and the highest effect was observed for the A375 cell line. These findings confirm that Fe₃O₄@Au@PEG-OH and Fe₃O₄@Au@PEG-NH₂ nanoparticles are promising photoactive agents for PTT, combining plasmonic and magnetic properties with biocompatibility.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118051"},"PeriodicalIF":6.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-quercetin complexes: methods of study, relevance to cell death pathways, therapeutic applications","authors":"Michael Kenneth Lawson","doi":"10.1016/j.biopha.2025.118055","DOIUrl":"10.1016/j.biopha.2025.118055","url":null,"abstract":"<div><div>Copper-quercetin complexes, CuQ, have been an active area of research for several decades. In vitro experiments show complexes are better antioxidants than quercetin alone. There seems to be a synergy effect. Cancer cell culture experiments also show prooxidant and DNA damaging properties which may be exploitable in cancer cell therapy. The effect of copper in combination with quercetin on cell death pathways needs to be investigated, especially regarding the cuproptosis pathway. CuQ complexes may require formulations similar to quercetin. The use of nanoparticles has enabled practical formulations of quercetin and/or their complexes to be made which guarantee stability, satisfactory bioavailability, and clinical effectiveness. In vivo studies are also being reported as well of planning of applications including skin infections and bone healing. Zn, Cu and quercetin tested on mice shows strong potential to treat Androgenic Alopecia. Copper-quercetin complexes seem to be easy to make and have good pharmacological potential in antimicrobial function, osteogenesis, angiogenesis and cancer treatment. Complexes such as those involving phenoanthroline, quercetin and copper may be found to be superior and zinc might be better for cancer therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118055"},"PeriodicalIF":6.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Nur77's mitochondrial apoptotic pathway: A promising therapeutic strategy for targeted disease intervention","authors":"Ruihai Fu ,&nbsp;Dandan Ling ,&nbsp;Qiqi Zhang ,&nbsp;Aifang Jiang ,&nbsp;Haiyan Pang","doi":"10.1016/j.biopha.2025.118091","DOIUrl":"10.1016/j.biopha.2025.118091","url":null,"abstract":"<div><div>The role of mitochondria in disease development cannot be overlooked, and the targeting of mitochondria for the treatment of disease has emerged as a significant area of research in recent years. Mitochondria are the control center of the intrinsic apoptotic pathway, and their normal functions are finely regulated by a series of complex mechanisms. The nuclear receptor Nur77 is closely related to the functions of the mitochondria and is an active pro-apoptotic member of the nuclear receptor superfamily. The translocation of Nur77 to the mitochondria can promote the conversion of the anti-apoptotic protein Bcl-2 to a pro-apoptotic state, disrupt the balance between mitochondrial fission and fusion, and inhibit mitophagy. These effects lead to irreversible damage to mitochondria and apoptosis, ultimately accelerating the progression of the disease. Here, we review the mechanism and targeted drug development of the mitochondrial apoptosis pathway activated by Nur77 in human diseases, helping to understand the new advances in disease treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118091"},"PeriodicalIF":6.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPRASP1 deletion in mice abrogates adverse side effects associated with chronic stimulation of Beta2-adrenoceptor","authors":"Alaa Abu-Helo ,&nbsp;François Daubeuf ,&nbsp;Thibaud Tranchant ,&nbsp;Christine Lehalle ,&nbsp;Khadija Elhabazi ,&nbsp;Gabrielle Zeder-Lutz ,&nbsp;Valérie Kugler ,&nbsp;Claire Lugnier ,&nbsp;Nelly Frossard ,&nbsp;Sandra Lecat ,&nbsp;Frédéric Simonin","doi":"10.1016/j.biopha.2025.118073","DOIUrl":"10.1016/j.biopha.2025.118073","url":null,"abstract":"<div><div>GPCR associated sorting protein 1 (GPRASP1) interacts with numerous GPCRs including the Beta2-adrenoceptor (B2AR) and has been proposed to be involved in adaptations associated with chronic stimulation of those receptors. In clinic, long acting B2AR agonists (LABAs) such as formoterol are used in the treatment of asthma as potent bronchodilators but with adverse side effects including the development of tolerance and airway hyperresponsiveness upon chronic administration. Here, we investigated the role of GPRASP1 on B2AR activity and on B2AR agonists-associated side effects <em>in vitro</em> and <em>in vivo</em>. To this purpose, we set-up a model of chronic formoterol administration in mouse leading to B2AR down-regulation as well as to the development of airway hyperreactivity and bronchodilator tolerance and studied the phenotype of GPRASP1 knockout animals. We show in cells that GPRASP1 expression has no impact on agonist-induced B2AR down-regulation but strongly modulate B2AR-associated signalling. Moreover, wild-type mice chronically treated with formoterol developed airway hyperresponsiveness to methacholine and bronchodilator tolerance to formoterol that were absent in GPRASP1 KO mice while B2AR down-regulation was similar in both genotypes. These adverse side effects were correlated with an increase in the number of cells and in collagen levels in the lungs of wild-type but not of GPRASP1 KO mice. Collectively, our data show that GPRASP1 is critically involved in adaptations to chronic activation of B2AR that leads to lung tissue remodelling, development of bronchial hyperresponsiveness and bronchodilator tolerance to B2AR agonist formoterol and could therefore represent an interesting target to limit side effects associated with LABAs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118073"},"PeriodicalIF":6.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of aggressive 4T1-luc metastatic breast cancer using immunogenic cell lysates generated with methotrexate","authors":"Luana Cristina Camargo ,&nbsp;Pedro Burgel ,&nbsp;Camila Magalhães Cardador ,&nbsp;Victor Carlos Mello ,&nbsp;Karen Letycia Rodrigues de Paiva ,&nbsp;Marina Mesquita Simões ,&nbsp;Raffael Júnio Araújo de Castro ,&nbsp;Isabel Martinello Valente ,&nbsp;Gabriel Ribeiro Farias ,&nbsp;Thais Bergmann de Castro ,&nbsp;Luís Alexandre Muehlmann ,&nbsp;Sônia Nair Báo ,&nbsp;João Paulo Figueiró Longo","doi":"10.1016/j.biopha.2025.118079","DOIUrl":"10.1016/j.biopha.2025.118079","url":null,"abstract":"<div><div>This study investigated a novel immunization therapy for pre-clinical aggressive metastatic breast cancer using immunogenic cell lysates derived from 4T1-luc cells treated with cisplatin and methotrexate, addressing the critical need for improved treatments given the poor prognosis associated with breast cancer metastasis and its significant mortality rate. Methotrexate, a conventional cytotoxic agent, demonstrated a previously unrecognized capacity to induce immunogenic cell lysates, presenting a potential drug repositioning opportunity. In a murine model of stage IV metastatic breast cancer, immunization with these lysates significantly reduced primary tumor growth and lung metastasis, as assessed by bioluminescence imaging. Immunization also modulated immune cell populations, reducing splenomegaly and hepatomegaly, and partially reversing the immunosuppressive phenotype associated with 4T1-luc tumor growth, as evidenced by cytokine profiling (IL-6 and IFN-γ) and flow cytometry analysis of CD4 + and CD8 + T cell subpopulations. Specifically, methotrexate-treated lysates induced a significant shift in CD4 + T cells towards an effector phenotype. These findings highlight the potential of this immunotherapy approach to improve breast cancer treatment outcomes and warrant further investigation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118079"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brucella inactivated vaccine elicits immunity against B. melitensis infection in mice and guinea pigs","authors":"Ruirui Hu ,&nbsp;Qianyi Zhang ,&nbsp;Wenjia Wang ,&nbsp;Wenhao Ren ,&nbsp;Mengxin Yao ,&nbsp;Yimei Xu ,&nbsp;Hui Zhang ,&nbsp;Jinliang Sheng ,&nbsp;Yong Wang ,&nbsp;Chuangfu Chen ,&nbsp;Zhongchen Ma","doi":"10.1016/j.biopha.2025.118077","DOIUrl":"10.1016/j.biopha.2025.118077","url":null,"abstract":"<div><h3>Background</h3><div>Brucellosis is a zoonotic disease that poses a significant threat to both animal husbandry and public health. Currently available vaccines for brucellosis are all live attenuated forms, which carry the risk of potential infectivity and provide a relatively limited range of protection. In contrast, inactivated vaccines are perceived to exhibit poor protective efficacy and fail to elicit effective cellular immunity. This study aimed to comprehensively evaluate the efficacy of the <em>Brucella</em> inactivated vaccine (CF) with the objective of developing a safer and more effective candidate for brucellosis vaccination.</div></div><div><h3>Methods</h3><div>Firstly, we evaluated the safety of CF in mice. Subsequently, we immunized mice with CF using various doses and methods, determining the optimal immunization dose and method through challenge testing. We evaluated the vaccine’s immunogenicity by detecting the cellular and humoral immune levels induced by CF in mice, and assessed the vaccine’s protective effect based on the post challenge organ bacterial load. Additionally, we evaluated the protective effects of dual doses and secondary immunization in guinea pigs.</div></div><div><h3>Results</h3><div>The results indicate that CF is safe and non-toxic; it induced significant increases in specific IgG antibody levels against <em>Brucella</em> during the early stages and markedly enhanced the T cell immune response, thereby promoting a Th1-biased immune response in mice. Following the challenge, CF demonstrated protective efficacy comparable to that of the S2 vaccine against <em>B. melitensis</em> biovar 3 infection in mice. CF-immunized guinea pigs were able to resist infection by <em>B. melitensis</em> M28 and <em>B. melitensis</em> biovar 3.</div></div><div><h3>Conclusions</h3><div>In summary, CF significantly induces both humoral and cellular immunity in mice. This study reports for the first time that a safe and effective inactivated <em>Brucella</em> vaccine (CF) can induce cellular immune responses and effectively prevent animal brucellosis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118077"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3,3’,5,5’-Tetramethoxybiphenyl-4,4’-diol exerts a cytotoxic effect on hepatocellular carcinoma cell lines by inducing morphological and ultrastructural alterations, G2/M cell cycle arrest and death by apoptosis via CDK1 interaction","authors":"Fabricio Seidy Ribeiro Inoue ,&nbsp;Virginia Marcia Concato-Lopes ,&nbsp;Bruna Taciane da Silva Bortoleti ,&nbsp;Ellen Mayara Souza Cruz ,&nbsp;Mariana Barbosa Detoni ,&nbsp;Fernanda Tomiotto-Pellissier ,&nbsp;Manoela Daiele Gonçalves-Lens ,&nbsp;Juliana Maria Bitencourt de Morais-Valentim ,&nbsp;Rayanne Regina Beltrame Machado ,&nbsp;Kaio Maciel Santiago-Silva ,&nbsp;Marcelle de Lima Ferreira Bispo ,&nbsp;Jéseka Gabriela Schirmann ,&nbsp;Aneli M. Barbosa-Dekker ,&nbsp;Robert F.H. Dekker ,&nbsp;Maria Claudia Terkelli de Assis ,&nbsp;Ivete Conchon-Costa ,&nbsp;Mário Sérgio Mantovani ,&nbsp;Danielle Lazarin-Bidóia ,&nbsp;Carolina Panis ,&nbsp;Wander Rogério Pavanelli","doi":"10.1016/j.biopha.2025.118082","DOIUrl":"10.1016/j.biopha.2025.118082","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with frequent recurrence and chemoresistance, underscoring the need for new treatment strategies. 3,3’,5,5’-Tetramethoxybiphenyl-4,4’-diol (TMBP) showed cytotoxicity against lung cancer cell lines without harming normal cells. Thus, we investigated the antitumoral effect of TMBP on HCC cell lines, HuH7.5 (p53-mutant) and HepG2/C3A (p53-wild type). Cells were treated with TMBP (12.5–150 µM) for 24 and 48 h, and metabolic cellular activity (MTT) were used to determine the 50 % inhibitory concentration (IC₅₀) values. TMBP cytotoxicity were assessed by Trypan blue assay, scanning and transmission electron microscopy. Cell migration (wound healing), total ROS (H₂DCFDA), mitochondrial dysfunction (TMRE), lipid droplets (Nile Red), and autophagic vacuoles (MDC) were assessed. Flow cytometry characterized cell cycle distribution and cell death. Caspase 3/7 activity and CASP3 expression confirmed apoptosis. Molecular docking and gene expression analysis validated TMBP-CDK1 interaction. TMBP reduced cell viability, with IC₅₀ values of 68 and 55 µM (HuH7.5) and 50 and 42 µM (HepG2/C3A) at 24 and 48 h. TMBP induced severe morphological alterations, impaired migration, increased ROS, mitochondrial dysfunction, increased lipid droplets and autophagic vacuoles. TMBP also led to G2/M arrest and apoptosis, likely via CDK1 inhibition through hydrogen bonding at Tyr15. These findings highlight TMBP as a promising therapeutic candidate targeting CDK1 in HCC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118082"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles and mechanisms of CDGSH iron-sulfur domain 1 in kainic acid-induced mitochondrial iron overload, dysfunction and neuronal damage","authors":"Jing Wang,&nbsp;Shuo Li,&nbsp;Haidong Xu,&nbsp;Jie Xue,&nbsp;Xiaorui Wan,&nbsp;Weilong Wu,&nbsp;Jiani Huang,&nbsp;Huiling Zhang,&nbsp;Zhenghong Qin,&nbsp;Yan Wang","doi":"10.1016/j.biopha.2025.118067","DOIUrl":"10.1016/j.biopha.2025.118067","url":null,"abstract":"<div><div>Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe^2 + remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using <em>in vivo</em> and <em>in vitro</em> excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118067"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}