Biomedicine & Pharmacotherapy最新文献

{"title":"Exacerbated cardiac dysfunction from combined alcohol binge and synthetic cannabinoid use","authors":"Janos Paloczi ,&nbsp;Ozge Gunduz-Cinar ,&nbsp;Burhan Yokus ,&nbsp;Bruno Paes-Leme ,&nbsp;György Haskó ,&nbsp;George Kunos ,&nbsp;Andrew Holmes ,&nbsp;Pal Pacher","doi":"10.1016/j.biopha.2025.118053","DOIUrl":"10.1016/j.biopha.2025.118053","url":null,"abstract":"<div><div>Alcohol remains the most frequently used intoxicant, posing a significant global health concern. Binge drinking has been linked to acute cardiovascular complications, including reduced cardiac performance, arrhythmias, and blood pressure instability. Additionally, there is a growing number of clinical reports describing severe adverse cardiac events associated with the recreational use of synthetic cannabinoids. Recent surveys reveal a troubling rise in polydrug misuse, particularly among young adults, with an increasing number of cases linked to fatal outcomes. This study aimed to characterize left ventricular performance in mice following combined acute alcohol and synthetic cannabinoid exposure using complex hemodynamic measurements via the pressure-volume (P-V) approach. Our findings revealed that alcohol ingestion or intravenous synthetic cannabinoid (CP55,940) administration led to a dose-dependent decline in systolic cardiac performance in mice. Moreover, the concurrent administration of alcohol and CP55,940 led to cardiodepression, surpassing the contractile dysfunction observed with each drug administered individually. Intravenous administration of the cannabinoid type-1 receptor (CB1R) antagonist rimonabant largely improved the combined drug administration-induced left ventricular contractile dysfunction in mice, while its intracerebroventricular administration resulted in only partial restoration of normal cardiac function, implicating a role for both central and peripheral CB1R signaling. Our results emphasize the severe cardiac consequences of simultaneous alcohol and synthetic cannabinoid misuse and offer a potential therapeutic avenue for mitigating the adverse cardiac effects of their combined use by repurposing CB1R antagonists.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118053"},"PeriodicalIF":6.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873901","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}

{"title":"Role of tumor suppressor genes P53 and PTEN in CD44-mediated gastric adenocarcinoma multidrug resistance","authors":"Laura Perez-Silva ,&nbsp;Elisa Herraez ,&nbsp;Rebeca P. Marijuan ,&nbsp;Maria Reviejo ,&nbsp;Elisa Lozano ,&nbsp;Luis Bujanda ,&nbsp;Mar Abad ,&nbsp;Rocio I.R. Macias ,&nbsp;Oscar Briz ,&nbsp;Jose J.G. Marin","doi":"10.1016/j.biopha.2025.118057","DOIUrl":"10.1016/j.biopha.2025.118057","url":null,"abstract":"<div><div>Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages, when curative options are limited and marked chemoresistance is already present. Although tumor suppressor genes (TSGs) are frequently altered in GAC, their impact on chemoresistance is not well understood. Gene expression data from The Cancer Genome Atlas cohort TCGA-STAD were validated by RT-qPCR in a Spanish cohort of GAC. In the human GAC cell line AGS, gene knocking-out was performed using CRISPR/Cas9. Cell viability (MTT-formazan test) and proliferation rate (digital holographic microscopy) were determined. Among the most frequently inactivated TSGs, <em>TP53</em>, <em>PTEN</em>, and <em>ARID1A</em> were selected for further studies. In GAC samples, <em>TP53</em> was upregulated, whereas <em>PTEN</em> and <em>ARID1A</em> were downregulated. Mutations in these TSGs led to a consistent alteration in the expression of their target genes. AGS cells exhibited TSG expression profiles like those observed in GAC, which supports their suitability as an <em>in vitro</em> model. Knocking-out <em>ARID1A</em> (ARID1A^KO) enhanced cell chemosensitivity. In contrast, silencing <em>TP53</em> (p53^KO) or <em>PTEN</em> (PTEN^KO) led to increased resistance to platinum-based drugs, doxorubicin, epirubicin, and docetaxel. Characterization of the resistome was performed using TaqMan Low-Density Arrays. In p53^KO and PTEN^KO cells, the expression of <em>UGT1A</em> and <em>CD44</em> was altered. Additional silencing of <em>CD44</em> in these cells partially reversed their chemoresistance. Moreover, pharmacological inhibition of CD44 with verbascoside sensitized p53^KO and PTEN^KO cells to anticancer drugs. In conclusion, dysfunctional <em>TP53</em> and <em>PTEN</em> contribute to altered drug responses of GAC. Moreover, we identified pharmacological vulnerabilities that could be useful to chemosensitize these tumors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118057"},"PeriodicalIF":6.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869510","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":"Piperine and its nanoformulations: A mechanistic review of their anti-cancer activities","authors":"Mahshad Ghasemi ,&nbsp;M. Hossein Nowroozzadeh ,&nbsp;Fereshteh Ghorat ,&nbsp;Aida Iraji ,&nbsp;Mohammad Hashem Hashempur","doi":"10.1016/j.biopha.2025.118075","DOIUrl":"10.1016/j.biopha.2025.118075","url":null,"abstract":"<div><div>Piperine, an active compound found in black pepper, exhibits promising anti-cancer properties by targeting critical signaling pathways involved in cancer cell proliferation, migration, and invasion. This review explores the diverse mechanisms through which piperine exerts its effects, including inhibition of the PI3K/Akt/mTOR and ERK1/2 pathways, activation of p38 and JNK pathways, and suppression of NF-kB/AP-1 signaling. Piperine disrupts Wnt/β-catenin signaling by inhibiting β-catenin nuclear translocation and TCF binding, thereby impairing cancer cell growth and metastasis. Additionally, piperine demonstrates anti-inflammatory actions by reducing CXCL8 expression and modulating the p38 MAPK and JNK pathways. To overcome the issues of low solubility and bioavailability, several nanoformulations of piperine<!--> <!-->were developed, such as polymer nanoparticles, nanoemulsion, liposomes, micelles, metal-organic frameworks and inorganic carriers, establishing promising cytotoxicity, prolonged-release, enhanced cellular influx, and directed drug delivery. The mechanisms involve G₀ and G₂/M arrest of the cell cycle, mitochondria-mediated apoptosis (involving Bax/Bcl-2 modulation and caspase activation), and cancer cell<!--> <!-->death. <em>In vivo</em> studies underscore the efficacy of piperine, while synergistic effects with other natural products and chemotherapy highlight its potential as a versatile therapeutic agent as an anticancer agent. These findings underscore piperine's potential as a multifaceted therapeutic agent for cancer treatment, emphasizing its diverse mechanisms of action and promising role in oncology.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118075"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858799","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":"Comparative effects of extracellular vesicles and liposomal nanocarriers on bleomycin-induced stress in A549 human adenocarcinoma cells","authors":"Thomas Conlon ,&nbsp;Maximilian Schaaf ,&nbsp;Ana Mateos-Maroto ,&nbsp;Sabrina Picciotto ,&nbsp;Svenja Morsbach ,&nbsp;Giorgia Adamo ,&nbsp;Shutian Si ,&nbsp;Ingo Lieberwirth ,&nbsp;Christine Rosenauer ,&nbsp;Katharina Landfester ,&nbsp;Antonella Bongiovanni ,&nbsp;Nicolas Touzet","doi":"10.1016/j.biopha.2025.118081","DOIUrl":"10.1016/j.biopha.2025.118081","url":null,"abstract":"<div><div>Lung cancer and chronic respiratory diseases are among the leading causes of death worldwide. Key factors in their pathogenesis include reactive oxygen species (ROS), transforming growth factor-β1 (TGF-β1) and epithelial-mesenchymal transition (EMT). Exogenous antioxidants can mitigate the oxidative stress that drives TGF-β1-mediated respiratory pathologies. Given their role in cellular communication and natural biocompatibility, extracellular vesicles (EVs) are emerging as promising candidates for the delivery of therapeutic cargo to pathological cells. Notably, microalgal-derived EVs (i.e., nanoalgosomes) have been shown to exhibit antioxidant and anti-inflammatory activity. In this study, the bioactivity of EVs derived from <em>Tetraselmis chuii</em> (CCAP 66/21B) was investigated in a bleomycin-stressed (8 µg mL⁻¹) human adenocarcinoma alveolar epithelial cell model (A549). Moreover, the effects of these EVs were compared to liposomes loaded with established therapeutics (pirfenidone and quercetin), synthesised using the lipid film hydration method. <em>In vitro</em> assessments included cell viability (MTS), intracellular ROS, morphological changes, cell migration, EMT-related mRNA expression (qPCR), and TGF-β1 release (ELISA). Both the EVs (nanoalgosomes) and pirfenidone- and quercetin-loaded liposomal nanocarriers (1–4 µg mL⁻¹) effectively attenuated bleomycin-induced EMT, inhibited cell migration, suppressed profibrotic TGF-β1, lowered intracellular ROS and upregulated glutathione peroxidase 4 (<em>GPX4</em>). Importantly, the innate bioactive cargo of the naturally derived nanoalgosomes exhibited comparable effects to the liposome therapeutic formulations in mitigating bleomycin-induced stress in A549 cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118081"},"PeriodicalIF":6.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864534","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}