Biomedicine & Pharmacotherapy最新文献

{"title":"Exploring SAR insights into royleanones for P-gp modulation","authors":"Gabrielle Bangay ,&nbsp;Vera M.S. Isca ,&nbsp;Florencia Z. Brauning ,&nbsp;Jelena Dinic ,&nbsp;Milica Pesic ,&nbsp;Bernardo Brito Palma ,&nbsp;Daniel J.V.A. dos Santos ,&nbsp;Ana M. Díaz-Lanza ,&nbsp;Eduardo Borges de Melo ,&nbsp;João Paulo Ataide Martins ,&nbsp;Patricia Rijo","doi":"10.1016/j.biopha.2025.117943","DOIUrl":"10.1016/j.biopha.2025.117943","url":null,"abstract":"<div><div>Multidrug resistance (MDR) poses a challenge in contemporary pharmacotherapy, significantly reducing the efficacy of chemotherapeutic agents. Among the array of mechanisms underpinning MDR, the upregulation of P-glycoprotein (P-gp), also known as MDR1 and encoded by the ABCB1 gene, emerges as an impediment in cancer treatment success. Plants from the <em>Plectranthus</em> genus (Lamiaceae) are recognised in traditional medicine for their diverse therapeutic applications. 7α-acetoxy-6β-hydroxyroyleanone (Roy), the principal diterpene derived from <em>Plectranthus grandidentatus</em> Gürke, has exhibited anti-cancer properties against various cancer cell lines. Previously synthesized ester derivatives of Roy have shown enhanced binding affinity with P-gp. This study utilises previously obtained <em>in vitro</em> data on P-gp activity of Roy derivatives to construct a ligand-based pharmacophore model elucidating critical features essential for P-gp modulation. Leveraging this data, we predict the potential of five novel ester derivatives of Roy to modulate P-gp <em>in vitro</em> against resistant NCI-H460 cells. A set of 16 previously synthesized royleanone derivatives underwent <em>in silico</em> structure-activity relationship (SAR) studies. A binary classification model, differentiating inactive and active compounds, generated 11,016 Molecular Interaction Field (MIF) descriptors from structures optimized at the DFT theory level. Following variable reduction and selection, a subset of 12 descriptors was identified, yielding a model with two latent variables (LV), utilizing only 34.14 % of the encoded information for calibration (LV1: 26.82 %; LV2: 7.32 %). Ultimately, prediction of the activity of new derivatives suggested all have a high likelihood of activity, which will be validated through future <em>in vitro</em> biological assays.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117943"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Ferroptosis in thyroid cancer: Potential mechanisms, effective therapeutic targets and predictive biomarker” [Biomed. Pharmacother. 177 (2024) 116971]","authors":"Yuying Chen ,&nbsp;Gang Pan ,&nbsp;Fan Wu ,&nbsp;Yu Zhang ,&nbsp;Yuanhui Li ,&nbsp;Dingcun Luo","doi":"10.1016/j.biopha.2025.117867","DOIUrl":"10.1016/j.biopha.2025.117867","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117867"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Cilostazol protects mice against myocardium ischemic/reperfusion injury by activating a PPAR?/JAK2/STAT3 pathway” [Biomed. Pharmacother. 94 (2017) 995–1001]","authors":"Jiangjin Li ,&nbsp;Xiaoli Xiang ,&nbsp;Xiaoxuan Gong ,&nbsp;Yafei Shi ,&nbsp;Jing Yang ,&nbsp;Zuo Xu","doi":"10.1016/j.biopha.2025.117890","DOIUrl":"10.1016/j.biopha.2025.117890","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117890"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Tacrolimus regulates extracellular vesicle secretion from T cells via autophagy-lysosomal pathway” [Biomed. Pharmacother. 182 (2025) 117765]","authors":"Chien-Chia Chen ,&nbsp;Tzu-Min Hung ,&nbsp;Yi-Jen Huang ,&nbsp;Hsu-Shan Hung ,&nbsp;Chun-Mei Hu ,&nbsp;Po-Huang Lee","doi":"10.1016/j.biopha.2025.117935","DOIUrl":"10.1016/j.biopha.2025.117935","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117935"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rifampicin and its neuroprotective properties in humans – A systematic review","authors":"Nina Vaezipour ,&nbsp;Sandra Bigi ,&nbsp;Rinn Song ,&nbsp;Nicole Ritz","doi":"10.1016/j.biopha.2025.117928","DOIUrl":"10.1016/j.biopha.2025.117928","url":null,"abstract":"<div><h3>Background</h3><div>Rifampicin is an antimicrobial drug used in the treatment of mycobacterial and gram-positive bacterial infections. <em>In vitro</em> studies suggest additional rifampicin-associated reduction of neurotoxicity. The aim of this study was to review the evidence for neuroprotective effects of rifampicin in infectious and non-infectious diseases in human studies.</div></div><div><h3>Methods</h3><div>A systematic literature search was done in MEDLINE and Embase including studies from 1 Jan 1946/47–20 Jan 2024, in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) (PROSPERO ID: CRD42022349852). Original articles investigating the effect of rifampicin on infections of the central nervous system (CNS) or on neurodegenerating diseases, were included. Screening, data extraction and risk of bias assessment were done using the Covidence software. Two authors assessed and extracted articles independently and blinded to each other.</div></div><div><h3>Results</h3><div>1438 articles were identified of which eight were included in the final analysis: Four studies included patients with infectious diseases and four studies with neurodegenerative diseases. A neuroprotective effect of rifampicin was shown in five studies. The studies found reduced inflammatory parameters in the cerebrospinal fluid, improved neurological outcome, less cognitive decline, less brain atrophy or less metabolic decline on imaging as an effect of rifampicin. One RCT showed worsening of cognitive assessment scales in neurodegenerative patients.</div></div><div><h3>Conclusion</h3><div>Current evidence suggests a neuroprotective effect of rifampicin in humans. As evaluation of neuroprotection is not standardized, a consensus definition for evaluation of clinical, radiological, and neuropsychological follow-up after pharmacological intervention would be helpful for future studies assessing neuroprotection.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117928"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAD+ modulation of intestinal macrophages renders anti-inflammatory functionality and ameliorates gut inflammation","authors":"Young-In Kim ,&nbsp;Inseok Ko ,&nbsp;Eun-Je Yi ,&nbsp;Jusik Kim ,&nbsp;Yong Rae Hong ,&nbsp;Wheeseong Lee ,&nbsp;Sun-Young Chang","doi":"10.1016/j.biopha.2025.117938","DOIUrl":"10.1016/j.biopha.2025.117938","url":null,"abstract":"<div><div>Macrophages can maintain gut immune homeostasis by driving clearance of infection, but also can prevent chronic inflammation and induce tissue repair. Reduced nicotinamide adenine dinucleotide (NAD⁺) levels in macrophages have been reported to be associated with the onset of severe colitis. Given that dysregulation of gut macrophages plays a significant role in inflammatory bowel disease (IBD), they represent a potential target for novel therapies. Here we show an IBD therapeutic candidate LMT503, a substrate that modulates NADH quinone oxidoreductase (NQO1), which induces anti-inflammatory macrophage polarization by NAD⁺ enhancement. To determine the anti-inflammatory effect of LMT503, a dextran sulfate sodium (DSS)-induced colitis mouse model was used in this study. Treatment of bone marrow-derived macrophages (BMDMs) with LMT503 increased IL-10 and Arg1 levels but decreased levels of TNF-α, iNOS, and IL-6. LMT503 also increased levels of SIRT1, SIRT3, and SIRT6, suggesting that macrophages were driven to an anti-inflammatory character. In a murine DSS-induced colitis model, oral treatment with LMT503 ameliorated colonic inflammation and decreased infiltrating monocytes and neutrophils. Although NAD⁺ enhancement did not alter CX₃CR1^intCD206^- or CX₃CR1^hiCD206⁺ colon macrophage population, it decreased levels of TNF-α and iNOS and increased IL-10 level, with colonic macrophages showing an anti-inflammatory character shift. Depletion of CX₃CR1 expressing gut resident macrophages abrogated the immune regulatory effect of LMT503 in the colon. These data suggest that LMT503 is a therapeutic candidate that can target macrophages to drive polarization with an immunosuppressive character and ameliorate IBD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117938"},"PeriodicalIF":6.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-miRNA therapeutics for uterine fibroids","authors":"Sharad Saxena ,&nbsp;Maria Concetta Volpe ,&nbsp;Chiara Agostinis ,&nbsp;Simone Vodret ,&nbsp;Nadja Anneliese Ruth Ring ,&nbsp;Andrea Colliva ,&nbsp;Roman Vuerich ,&nbsp;Luca Braga ,&nbsp;A. Cook-Calvete ,&nbsp;Federico Romano ,&nbsp;Gabriella Zito ,&nbsp;Giovanni Di Lorenzo ,&nbsp;Blendi Ura ,&nbsp;Giuseppe Ricci ,&nbsp;Maurizio Pinamonti ,&nbsp;Roberta Bulla ,&nbsp;Serena Zacchigna","doi":"10.1016/j.biopha.2025.117946","DOIUrl":"10.1016/j.biopha.2025.117946","url":null,"abstract":"<div><h3>Background</h3><div>Uterine leiomyomas arise from altered uterine smooth muscle cell proliferation in the myometrium. Available treatments are limited and fraught with major side effects. Here, we leveraged data from a high-throughput screening using human microRNA mimics and selected miR-148a-3p as a therapeutic target. The study aimed to assess the therapeutic potential of a miR-148a-3p inhibitor in suppressing the proliferation of uterine leiomyoma cells and in a xenograft mouse model.</div></div><div><h3>Methods</h3><div>Clinical samples of uterine leiomyoma were used to isolate primary uterine leiomyoma cells and develop a subcutaneous xenograft mouse model. Cells were transfected with both miR-148a-3p mimic and anti-miR-148a-3p to assess the effect of miR-148a-3p on-cell proliferation. Animals were administered anti-miR-148a-3p-LNA via both local (intra-tumoral) and systemic (intraperitoneal) routes. Tumor volume was measured using ultrasonography, followed by histological and immunofluorescence staining, and target gene expression analysis.</div></div><div><h3>Results</h3><div>Transfection of primary cells with miR-148a-3p mimic resulted in increased smooth-muscle cell proliferation, whereas anti-miR-148a-3p LNA reduced their proliferation. Both local and systemic delivery of anti-miR-148a-3p LNA reduced tumor volume and cell proliferation. Anti-miR-148a-3p LNA also led to reduced levels of miR-148a-3p <em>in vivo,</em> paralleled by the up-regulation of its target genes TXNIP and Nrp1.</div></div><div><h3>Conclusion</h3><div>Anti-miR-148a-3p LNA inhibits the proliferation of patient-derived leiomyoma cells and tumor growth <em>in vivo</em>, by suppressing miR-148a-3p levels and increasing TXNIP and Nrp1 gene expression. The highest therapeutic effect was observed with systemic administration, positioning miR-148a-3p inhibition as a promising therapeutic strategy for uterine leiomyoma in humans.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117946"},"PeriodicalIF":6.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenothiazines boost host control of Mycobacterium avium infection in primary human macrophages","authors":"Gül Kilinç,&nbsp;Tom H.M. Ottenhoff,&nbsp;Anno Saris","doi":"10.1016/j.biopha.2025.117941","DOIUrl":"10.1016/j.biopha.2025.117941","url":null,"abstract":"<div><div><em>Mycobacterium avium</em> (<em>Mav</em>) complex is the leading cause of pulmonary diseases associated with non-tuberculous mycobacterial (NTM) infections worldwide. The inherent and increasing acquired antibiotic resistance of <em>Mav</em> hampers the treatment of <em>Mav</em> infections and emphasizes the urgent need for alternative treatment strategies. A promising approach is host-directed therapy (HDT), which aims to boost the host’s immune defenses to combat infections. In this study, we show that phenothiazines, particularly trifluoperazine (TFP) and chlorproethazine (CPE), restricted <em>Mav</em> survival in primary human macrophages. Notably, TFP and CPE did not directly inhibit mycobacterial growth at used concentrations, confirming these drugs function through host-dependent mechanisms. TFP and CPE induced a mild, albeit not statistically significant, increase in autophagic flux along with the nuclear intensity of transcription factor EB (TFEB), the master transcriptional regulator of autophagy. Inhibition of autophagic flux with bafilomycin, however, did not impair the improved host infection control by TFP and CPE, suggesting that the host (auto)phagolysosomal pathway is not causally involved in the mechanism of action of TFP and CPE. Additionally, TFP and CPE increased the production of both cellular and mitochondrial reactive oxygen species (ROS). Scavenging mitochondrial ROS did not impact, whereas inhibition of NADPH oxidase (NOX)-mediated ROS production partially impaired the HDT activity of TFP and CPE, indicating that oxidative burst may play a limited role in the improved host control of <em>Mav</em> infection by these drugs. Overall, our study demonstrates that phenothiazines are promising HDT candidates that enhance the antimicrobial response of macrophages against <em>Mav</em>, through mechanism(s) that were partially elucidated.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117941"},"PeriodicalIF":6.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Cyanocinnamylboronic acid derivatives are safe, selective anti-inflammatory molecules that inhibit P2X7 receptor function and signaling","authors":"Noemi de Jesus Hiller ,&nbsp;Juliana Pimenta Salles ,&nbsp;Lucas Villas Bôas Hoelz ,&nbsp;Bruna Costa Zorzanelli ,&nbsp;Tácio Vinicio Amorim Fernandes ,&nbsp;Nubia Boechat ,&nbsp;Daniela de Luna Martins ,&nbsp;Robson Xavier Faria","doi":"10.1016/j.biopha.2025.117945","DOIUrl":"10.1016/j.biopha.2025.117945","url":null,"abstract":"<div><div>P2X7 purinergic receptor (P2X7R) is a promising target for the development of new anti-inflammatory therapies. This can be inferred from the number of pharmaceutical patents aimed at inhibitors of this receptor and the number of clinical trials related to P2X7 in progress. A previous study demonstrated that α-cyanocinnamylboronic acid derivatives can be valuable starting points for designing P2X7 inhibitors. Encouraged by previous results, new 2-cyanocinamic boronic acids were prepared and evaluated for their cytotoxicity, ability to inhibit human and mouse P2X7 receptors, and anti-inflammatory effects <em>in vitro</em> and <em>in vivo</em> in ATP-induced mouse paw edema. In the present work, a series of 2-cyanocinamic boronic acids were evaluated for their effects on the function and intracellular signaling of the purinergic receptor P2X7. Additionally, the anti-inflammatory properties of the series were investigated through <em>in vitro</em> and <em>in vivo</em> experiments. The selectivity and affinity for inhibiting the P2X7 receptor were investigated in U937 cells via <em>in silico</em> assays. We observed that <strong>3 l</strong> inhibited P2X7 receptor function and intracellular signaling <em>in vitro</em> and inflammation <em>in vivo</em> after binding to P2X7 receptor allosteric sites.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117945"},"PeriodicalIF":6.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on ferroptosis in cerebral hemorrhage","authors":"Niping Mao ,&nbsp;Min Zhang ,&nbsp;Ming Shen ,&nbsp;Junhui Yuan ,&nbsp;Zhenlang Lin","doi":"10.1016/j.biopha.2025.117932","DOIUrl":"10.1016/j.biopha.2025.117932","url":null,"abstract":"<div><div>The pathophysiology of intracerebral hemorrhage (ICH) is complex and can cause variable degrees of cell death. Recently, ferroptosis, an emerging cell death mechanism, has garnered significant attention in cerebral hemorrhage disorder. This study aimed to examine iron mortality after cerebral hemorrhage and current targets for potential therapeutic interventions. We specifically focused on iron metabolism abnormalities, lipid peroxidation, and related neuroinflammation and introduced molecular mechanisms, including transcription factors, to gain a better understanding of the underlying mechanisms of ferroptosis and investigate possible therapeutic options for ICH.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"185 ","pages":"Article 117932"},"PeriodicalIF":6.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}