Biomedicine & Pharmacotherapy最新文献

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Magnolol facilitates mitochondrial-peroxisome dysfunction and induces oxeiptosis in lung cancer cells following transfer via tunneling nanotubes 厚朴酚促进线粒体-过氧化物酶体功能障碍,诱导肺癌细胞通过隧道纳米管转移
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-09 DOI: 10.1016/j.biopha.2025.118126
Meng-Hsuan Cheng , Hsiao-Hsuan Wang , Mo Da-Sang Hua , Hsuan-Fu Kuo , Zi-Jing Lin , Chong-Chao Hsieh , Chih-Hsin Hsu , Chia-Yang Li , Shu-Chi Wang , Yung-Hsiang Chen , Szu-Hui Wu , Wei-Lun Liu , Po-Len Liu
{"title":"Magnolol facilitates mitochondrial-peroxisome dysfunction and induces oxeiptosis in lung cancer cells following transfer via tunneling nanotubes","authors":"Meng-Hsuan Cheng ,&nbsp;Hsiao-Hsuan Wang ,&nbsp;Mo Da-Sang Hua ,&nbsp;Hsuan-Fu Kuo ,&nbsp;Zi-Jing Lin ,&nbsp;Chong-Chao Hsieh ,&nbsp;Chih-Hsin Hsu ,&nbsp;Chia-Yang Li ,&nbsp;Shu-Chi Wang ,&nbsp;Yung-Hsiang Chen ,&nbsp;Szu-Hui Wu ,&nbsp;Wei-Lun Liu ,&nbsp;Po-Len Liu","doi":"10.1016/j.biopha.2025.118126","DOIUrl":"10.1016/j.biopha.2025.118126","url":null,"abstract":"<div><div>Recent therapeutic advances have improved survival rates for patients with lung cancer. However, drug resistance remains a significant challenge and is closely linked to mitochondrial alterations in lung cancer cells. Magnolol, a compound extracted from <em>Magnolia officinalis</em>, has anti-cancer properties. However, its impact on mitochondria in cancer cells remains poorly understood. This study aimed to explore the therapeutic potential of Magnolol in lung cancer and elucidate its effects on mitochondria in lung cancer cells. The effects of Magnolol on lung cancer were studied using xenograft mouse studies and <em>in vitro</em> analyses. Magnolol promotes the production of reactive oxygen species (ROS) and inhibits the antioxidant pathway in cancer cells. This disruption further impairs redox interactions between mitochondria and peroxisome, leading to mitochondrial dysfunction and mitocytosis. Additionally, Magnolol activates oxeiptosis, facilitating intercellular transport of damaged mitochondria and peroxisomes via tunneling nanotubes. The increased fusion of mitochondria may contribute to mitochondrial dysfunction, promote the accumulation of dysfunctional peroxisomes in recipient cells, and elevate ROS levels. In turn, this process enhances oxeiptosis, ultimately inhibiting tumour progression. These findings suggest that Magnolol may serve as a promising targeted therapeutic for disrupting mitochondrial function in lung cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118126"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929336","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}
引用次数: 0
Antigen presentation potential is variable among human ovarian tumour and syngeneic murine models and dictates pre-clinical outcomes of immunotherapy 抗原呈递潜能在人卵巢肿瘤和同基因小鼠模型中是可变的,并决定了免疫治疗的临床前结果
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-09 DOI: 10.1016/j.biopha.2025.118141
Louisa Alim , Siddharth Adityan , Rui Chen , Trent Neilson , Elaina Coleborn , Andrew N. Wilkinson , Yaowu He , Gowri Irgam , Chintan Bhavsar , Rohan Lourie , Rebecca Rogers , Nimithri Cabraal , Nisha Jagasia , Naven Chetty , Lewis Perrin , John D. Hooper , Raymond Steptoe , Sherry Y. Wu
{"title":"Antigen presentation potential is variable among human ovarian tumour and syngeneic murine models and dictates pre-clinical outcomes of immunotherapy","authors":"Louisa Alim ,&nbsp;Siddharth Adityan ,&nbsp;Rui Chen ,&nbsp;Trent Neilson ,&nbsp;Elaina Coleborn ,&nbsp;Andrew N. Wilkinson ,&nbsp;Yaowu He ,&nbsp;Gowri Irgam ,&nbsp;Chintan Bhavsar ,&nbsp;Rohan Lourie ,&nbsp;Rebecca Rogers ,&nbsp;Nimithri Cabraal ,&nbsp;Nisha Jagasia ,&nbsp;Naven Chetty ,&nbsp;Lewis Perrin ,&nbsp;John D. Hooper ,&nbsp;Raymond Steptoe ,&nbsp;Sherry Y. Wu","doi":"10.1016/j.biopha.2025.118141","DOIUrl":"10.1016/j.biopha.2025.118141","url":null,"abstract":"<div><div>High grade serous ovarian carcinoma (HGSC) is a fatal gynaecological malignancy with limited therapeutic options. Immunotherapies targeting MHC-I-dependent antigen presentation offer potential. Currently, the antigen presentation machinery (APM) of widely used syngeneic murine HGSC models remains poorly characterised, limiting translational relevance. Here, we systematically evaluate APM gene expression in syngeneic murine and patient samples. <em>Tap1</em> and <em>Psmb8</em> were identified as critical APM markers, deficient in murine models and strongly correlating with MHC-I expression. Hierarchical clustering correlation analysis using these markers revealed that ID8-p53<sup>⁻/⁻</sup>BRCA1<sup>⁻/⁻</sup> was the most strongly correlated model and aligned with the largest patient subset. Moreover, ID8-ip1 correlated to the smaller second patient subset strongly. The low MHC-I expressing IG10 model was unique clustering alongside patient derived LP28 tumour and not fitting either patient subset. <em>In vivo</em> test of a novel combination immune therapy consisting of Flt3L, Poly(I:C), and paclitaxel therapy demonstrated significantly reduced tumour burden in high APM models (p53⁻/⁻BRCA1⁻/⁻, ID8-ip1; p &lt; 0.01), but not IG10. Furthermore, high expressing MHC-I models were linked to enhanced DC expansion, CD8⁺ T-cell infiltration, and effector differentiation (131 % increase in ID8-ip1), alongside improved CD8⁺ T-cell activation and CD86⁺ B-cell co-stimulation. These findings establish MHC-I as a predictive biomarker for immunotherapy response and underscore the need for APM-enhancing strategies in antigen-poor tumours. By bridging murine models to human APM heterogeneity, this work provides a framework for optimising preclinical immunotherapy evaluation and patient stratification, advancing tailored therapeutic approaches for HGSC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118141"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921986","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}
引用次数: 0
Enhancing oxime efficacy into brain using ultrasound to counteract nerve agent exposure 利用超声波增强肟进入大脑的功效,以抵消神经毒剂的暴露
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-09 DOI: 10.1016/j.biopha.2025.118120
Lépinard Lucie , Leterrier Sarah , Jourdain Laurène , Turri Louise , Belkebir Assia , Knoertzer Julie , Champault Alexandre , Bel Rosalie , Selingue Erwan , Mériaux Sébastien , Larrat Benoit , Tournier Nicolas , Dal Bo Grégory , Thibault Karine , Novell Anthony
{"title":"Enhancing oxime efficacy into brain using ultrasound to counteract nerve agent exposure","authors":"Lépinard Lucie ,&nbsp;Leterrier Sarah ,&nbsp;Jourdain Laurène ,&nbsp;Turri Louise ,&nbsp;Belkebir Assia ,&nbsp;Knoertzer Julie ,&nbsp;Champault Alexandre ,&nbsp;Bel Rosalie ,&nbsp;Selingue Erwan ,&nbsp;Mériaux Sébastien ,&nbsp;Larrat Benoit ,&nbsp;Tournier Nicolas ,&nbsp;Dal Bo Grégory ,&nbsp;Thibault Karine ,&nbsp;Novell Anthony","doi":"10.1016/j.biopha.2025.118120","DOIUrl":"10.1016/j.biopha.2025.118120","url":null,"abstract":"<div><div>Organophosphates (OP) found in pesticides and chemical weapons irreversibly inhibit acetylcholinesterases (AChE) and cause toxic accumulation of acetylcholine throughout the organism. Due to their lipophilicity, OP easily cross the blood-brain barrier (BBB) and affect the central nervous system (CNS), resulting in epileptic seizures and long-term cognitive impairment. The antidote includes oximes which reactivate inhibited AChE. Unfortunately, oximes have limited BBB penetration and therefore fail to prevent neurological damage. Improving the penetration of oximes through the CNS and their therapeutic effect on the brain, is a major challenge. Recent studies have demonstrated the efficacy of transcranial focused ultrasound (FUS), in combination to intravenously injected microbubbles, to transiently disrupt the BBB for drug delivery. We assessed the efficacy of FUS to deliver two known oximes (2-PAM, HI-6) into the brain and reactivate AChE following an exposure to VX in a mouse model. After both sub-lethal and supra-lethal exposure, HI-6 + FUS treatment reactivated nearly 30 % more AChE in the hippocampus than HI-6 alone. In contrast, 2-PAM+FUS was not effective. Furthermore, animals treated with HI-6 + FUS following an exposure to a supra-lethal dose of VX exhibited enhanced short-term recovery and an increased 24 hours survival rate. Finally, up to 7 days after exposure to a supra-lethal dose of VX, HI-6 + FUS showed a significant reduction of pro-inflammatory cytokines IL-6 and MIP-1α expression levels in the hippocampus. Thus, the use of FUS is very promising for improving the medical care of OP exposure because it enables antidotes to treat central symptoms and it may reduce brain damage.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118120"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921987","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}
引用次数: 0
Inhibitory effects of kukoamine B on adipogenesis and lipid accumulation in vitro and obesity in vivo 苦参胺B对体外脂肪形成和脂质积累及体内肥胖的抑制作用
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-09 DOI: 10.1016/j.biopha.2025.118143
Kang-Il Oh , Su-Jin Lee , Jeonghyun Kim , Junhwan Jeong , Mun Hyoung Bae , Eunkuk Park , Seon-Yong Jeong
{"title":"Inhibitory effects of kukoamine B on adipogenesis and lipid accumulation in vitro and obesity in vivo","authors":"Kang-Il Oh ,&nbsp;Su-Jin Lee ,&nbsp;Jeonghyun Kim ,&nbsp;Junhwan Jeong ,&nbsp;Mun Hyoung Bae ,&nbsp;Eunkuk Park ,&nbsp;Seon-Yong Jeong","doi":"10.1016/j.biopha.2025.118143","DOIUrl":"10.1016/j.biopha.2025.118143","url":null,"abstract":"<div><div>Obesity, characterized by excessive adipose tissue accumulation, is an important risk factor for the development of several chronic conditions, including cardiovascular disease, type 2 diabetes mellitus, and hypertension. The present study aimed to investigate the effects of kukoamine B (KB), a major component of the <em>Lycii Radicis</em> Cortex (LRC), on adipogenesis and lipid accumulation <em>in vitro</em> and further assess its role in obesity <em>in vivo</em>. For the <em>in vitro</em> experiments, 3T3-L1 cells and primary-cultured adipose-derived stem cells were used. Lipid accumulation was measured using Oil Red O staining, and adipogenesis-related gene expression was assessed using quantitative reverse transcription polymerase chain reaction. For the <em>in vivo</em> experiments, LRC or KB was orally administered to ovariectomized and high-fat diet-induced obese mice. LRC exhibited antiadipogenic and antiobesity effects <em>in vitro</em> and <em>in vivo</em> experiments. Fractionation of the LRC extract identified KB as a bio-active component. KB treatment resulted in a dose-dependent reduction in lipid droplet formation and downregulation of adipogenesis-related genes, including <em>Pparg</em>, <em>Cebpa</em>, <em>Srebp1</em>, <em>Fasn</em>, and <em>Plin2</em>, in both cell types. Western blot analysis revealed that KB significantly suppressed the protein expression of key adipogenic factors, including phosphorylated CREB, CEBPB, PPARG, and CEBPA. <em>In vivo</em>, KB administration significantly reduced body weight gain, hepatic steatosis, and adipocyte hypertrophy in both mouse models. These results suggest that KB is a potential therapeutic agent for the prevention and treatment of obesity. Further rigorous investigations, including human clinical trials, are necessary to fully elucidate the safety profile, optimal dosing regimens, and long-term effects of KB.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118143"},"PeriodicalIF":6.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921988","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}
引用次数: 0
Hydroxychloroquine can reduce fetal growth restriction in a dexamethasone-induced rat model 羟氯喹可以减轻地塞米松诱导的大鼠胎儿生长受限
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-08 DOI: 10.1016/j.biopha.2025.118084
Minji Choi , Jae Ryoung Hwang , Ji-Hee Sung , Suk-Joo Choi , Jung-Sun Kim , Cheong-Rae Roh , Soo-young Oh
{"title":"Hydroxychloroquine can reduce fetal growth restriction in a dexamethasone-induced rat model","authors":"Minji Choi ,&nbsp;Jae Ryoung Hwang ,&nbsp;Ji-Hee Sung ,&nbsp;Suk-Joo Choi ,&nbsp;Jung-Sun Kim ,&nbsp;Cheong-Rae Roh ,&nbsp;Soo-young Oh","doi":"10.1016/j.biopha.2025.118084","DOIUrl":"10.1016/j.biopha.2025.118084","url":null,"abstract":"<div><div>Fetal growth restriction (FGR) is a major cause of neonatal mortality, but no therapeutic options are available for the intrauterine period. Hydroxychloroquine (HCQ), a drug used to treat malaria and autoimmune diseases, reportedly has beneficial effects on pregnancy outcomes in women with lupus or antiphospholipid antibody syndrome, which is often associated with FGR. We investigated the effect of HCQ on fetal growth using a dexamethasone (DEX)-induced FGR rat model. Pregnant Sprague–Dawley rats were divided into three groups (n = 10 for each group): control, DEX (using an osmotic pump), and DEX plus HCQ (administered on gestational days 13–19). All animals were sacrificed on gestational day 20. The weight of each pup was recorded. Maternal serum and placental proteins in each group were compared using an Olink proteomics tool. Administration of DEX induced the FGR (&lt;10th percentile; <em>P</em> &lt; 0.001) , which was marginally recovered by HCQ (<em>P</em> = 0.087). However, systolic blood pressure, serum soluble fms-like kinase-1 levels, and placental thickness were not affected by DEX or the addition of HCQ. Olink proteomic analysis revealed that multiple maternal serum proteins involved in embryonic and placental development were significantly decreased in the DEX-induced FGR rat model but restored by HCQ. Our data showed that HCQ partially restored decreased fetal weight in DEX-induced FGR rats, and these changes involved embryonic and placental development-related signaling pathways during pregnancy. Collectively, these results suggest that HCQ can serve a therapeutic drug to mitigate intrauterine FGR.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118084"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916686","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}
引用次数: 0
Berberine promotes apoptosis and inhibits the migration of oral squamous carcinoma cells through inhibition of the RAGE/PI3K/AKT/mTOR pathway 小檗碱通过抑制RAGE/PI3K/AKT/mTOR通路促进口腔鳞癌细胞凋亡,抑制口腔鳞癌细胞迁移
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-08 DOI: 10.1016/j.biopha.2025.118147
Daili Liu , Ling Li , Jingfei Zhang , Han Qin , Meng Zhang , Xiaoyang Sun , Yuting Han , Feng Wang , Zhi Wang , Zhen Cai
{"title":"Berberine promotes apoptosis and inhibits the migration of oral squamous carcinoma cells through inhibition of the RAGE/PI3K/AKT/mTOR pathway","authors":"Daili Liu ,&nbsp;Ling Li ,&nbsp;Jingfei Zhang ,&nbsp;Han Qin ,&nbsp;Meng Zhang ,&nbsp;Xiaoyang Sun ,&nbsp;Yuting Han ,&nbsp;Feng Wang ,&nbsp;Zhi Wang ,&nbsp;Zhen Cai","doi":"10.1016/j.biopha.2025.118147","DOIUrl":"10.1016/j.biopha.2025.118147","url":null,"abstract":"<div><div>Given the high recurrence rate, elevated risk of metastasis, and drug resistance associated with oral squamous cell carcinoma (OSCC), the development of low - toxicity and highly efficient therapeutic agents has emerged as a top research priority. In this study, we conducted an in-depth investigation into the efficacy and underlying mechanism of berberine (BBR), a compound renowned for its broad anticancer activity, in the context of OSCC. Using network pharmacology, we identified 91 potential targets of BBR in OSCC, with SRC, PIK3CA, and CDC42 ranking among the top. KEGG pathway analysis indicated that the cross-targets were predominantly concentrated in signaling pathways such as PI3K/AKT, AGE-RAGE, and Ras. Molecular docking assays demonstrated that the binding energies between BBR and the core targets were all below −5 kcal/mol, signifying favorable binding interactions. Bioinformatics studies unveiled that SRC, PIK3CA, and CDC42 were highly expressed in OSCC patients and correlated with a poorer prognosis. In vitro, experiments further substantiated that BBR impeded the proliferation and migration of OSCC cells and reduced the intracellular expression levels of RAGE, p-PI3K, p-AKT, and p-mTOR proteins. Our results suggest that BBR effectively facilitates apoptosis and curbs the proliferation and migration of OSCC, potentially by suppressing the RAGE/PI3K/AKT/mTOR pathway. In summary, these findings underscore the potential of BBR as a single agent capable of exerting multi-target and multi-pathway synergistic effects on cancer cells.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118147"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916687","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}
引用次数: 0
Myeloid-specific deficiency of group VIA calcium-independent phospholipase A2 preconditions myeloid cells for injury resolution after acetaminophen exposure 对乙酰氨基酚暴露后,髓细胞特异性缺乏钙不依赖磷脂酶A2是髓细胞损伤消退的先决条件
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-08 DOI: 10.1016/j.biopha.2025.118146
Feng Xu , Chutima Jansakun , Gang Li , Uddipta Biswas , Gernot Poschet , Simone Staffer , Sabine Tuma-Kellner , Inaam Nakchbandi , Uta Merle , Walee Chamulitrat
{"title":"Myeloid-specific deficiency of group VIA calcium-independent phospholipase A2 preconditions myeloid cells for injury resolution after acetaminophen exposure","authors":"Feng Xu ,&nbsp;Chutima Jansakun ,&nbsp;Gang Li ,&nbsp;Uddipta Biswas ,&nbsp;Gernot Poschet ,&nbsp;Simone Staffer ,&nbsp;Sabine Tuma-Kellner ,&nbsp;Inaam Nakchbandi ,&nbsp;Uta Merle ,&nbsp;Walee Chamulitrat","doi":"10.1016/j.biopha.2025.118146","DOIUrl":"10.1016/j.biopha.2025.118146","url":null,"abstract":"<div><div>Genetic PLA2G6 variants are associated with C-reactive protein in humans. Myeloid-specific PLA2G6-deficient (Pla2g6<sup>M-/-</sup>) mice show increased hepatic myeloperoxidase and recruitment of granulocytes in response to lipopolysaccharide (LPS). We hypothesized that Pla2g6<sup>M-/-</sup> mice could be protected from acetaminophen (APAP) hepatotoxicity whereby neutrophils, eosinophils, and alternatively activated macrophages are reportedly protective. Herein, Pla2g6<sup>M-/-</sup> mice treated with 300 mg/kg APAP for 24 h showed attenuated hepatic necrosis and plasma cytokines, and with elevated levels of Ly6C<sup>lo</sup> in peripheral blood mononuclear cells and plasma lipoxin A4. Remarkably, bone-marrow-derived macrophages (BMDMs) from untreated Pla2g6<sup>M-/-</sup> mice exhibited elevated baseline expression of cPLA2α, NOX2, Rac1, Arg-1, phospho-MLKL, and iNOS protein, which was exacerbated by LPS <em>in vitro</em>. APAP administration preconditioned Pla2g6<sup>M-/-</sup> BMDMs for further activation of enzymes involving in phagocytosis (Rac1 and phospho-MLKL) and eicosanoids (COX2 and A15LOXB). Pla2g6<sup>M-/-</sup> BMDMs showed an increased release of pro-resolution lipid mediators lipoxin A4, PGE2, and 15d-PGJ2, which was further elevated by LPS <em>in vitro</em> or APAP <em>in vivo</em>. Phagocytic gene signatures (myeloperoxidase and NOX2) were also upregulated in livers of untreated and APAP-treated Pla2g6<sup>M-/-</sup> mice. APAP protection in Pla2g6<sup>M-/-</sup> mice was associated with increased proportion of neutrophils (Ly6G), eosinophils (eosinophilic cationic protein), and M2 macrophages (CD206) in/at the portal tract and central vein as determined by immunohistochemistry. Thus, myeloid-specific PLA2G6 deficiency preconditioned macrophages for eicosanoid and phagocytic pathways rendering protection against APAP hepatotoxicity. Our results may be applicable to patients with PLA2G6 mutations, and PLA2G6 inhibition specifically in myeloid cells may represent a new strategy to alleviate APAP poisoning.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118146"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916688","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}
引用次数: 0
Inhibition of the PI3K/AKT signaling pathway contributes to the anti-renal cell carcinoma effects of deoxyelephantopin 抑制PI3K/AKT信号通路参与脱氧象皮苷抗肾细胞癌作用
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-08 DOI: 10.1016/j.biopha.2025.118136
Jinjin He , Lut Yi Wong , Si Chen , Shi-Jia Zhang , Wei Chen , Jing-Xuan Bai , Li Wang , Xiao-Qi Wang , Sze-Man Amy Li , Qinglin Li , Xiu-Qiong Fu , Zhi-Ling Yu
{"title":"Inhibition of the PI3K/AKT signaling pathway contributes to the anti-renal cell carcinoma effects of deoxyelephantopin","authors":"Jinjin He ,&nbsp;Lut Yi Wong ,&nbsp;Si Chen ,&nbsp;Shi-Jia Zhang ,&nbsp;Wei Chen ,&nbsp;Jing-Xuan Bai ,&nbsp;Li Wang ,&nbsp;Xiao-Qi Wang ,&nbsp;Sze-Man Amy Li ,&nbsp;Qinglin Li ,&nbsp;Xiu-Qiong Fu ,&nbsp;Zhi-Ling Yu","doi":"10.1016/j.biopha.2025.118136","DOIUrl":"10.1016/j.biopha.2025.118136","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC) is the most common kidney cancer. Despite advances in treatment, current therapeutic strategies are often limited by side effects, drug resistance, and low response rates, necessitating alternatives for RCC treatment. Deoxyelephantopin (DEO), a sesquiterpene lactone from Elephantopi Herba, has demonstrated anticancer properties in multiple cancer models; however, its effects on RCC remain unknown. This study aimed to investigate the anti-RCC effects of DEO and its underlying molecular mechanisms. Human RCC cell lines (786-O, Caki-1, A498) and a murine RCC cell line (RENCA) were used for <em>in vitro</em> assays. Results revealed that DEO dose-dependently inhibited cell viability and colony formation in 786-O, Caki-1, A498, and RENCA cells, while also inducing apoptosis in 786-O and Caki-1 cells. A RENCA allograft mouse model was used for <em>in vivo</em> assays. DEO significantly suppressed tumor growth without causing notable changes in body weight, organ coefficients, or serum biochemical markers (ALT, AST, BUN, Cr). Network pharmacology analysis predicted the PI3K/AKT signaling pathway as a key mediator of DEO's anti-RCC effects. Western blotting showed that DEO downregulated the expression of EGFR, p-EGFR (Tyr1068), PI3K p110α, p-Akt (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), 4E-BP1, p-4E-BP1 (Thr37/46), HIF-1α, and Bcl-2. Overactivation of AKT attenuated DEO's inhibitory effects on cell viability in 786-O cells. In conclusion, this study is the first to demonstrate that DEO exerts anti-RCC effects in both cellular and animal models, primarily through inhibition of the PI3K/AKT pathway. These findings suggest that DEO holds promise as a lead compound for RCC management.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118136"},"PeriodicalIF":6.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916600","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}
引用次数: 0
Comparison between the effect of ethanolic extract of Urtica urens L. and bisphosphonate in the treatment of induced osteoporosis in rats 荨麻醇提物与双膦酸盐对大鼠诱导性骨质疏松症的治疗作用比较
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-07 DOI: 10.1016/j.biopha.2025.118112
Massara Mzid , Maha Ben Jemaa , Khansa Chaabouni , Fatma Ayedi , Zouheir Sahnoun , Tarek Rebai
{"title":"Comparison between the effect of ethanolic extract of Urtica urens L. and bisphosphonate in the treatment of induced osteoporosis in rats","authors":"Massara Mzid ,&nbsp;Maha Ben Jemaa ,&nbsp;Khansa Chaabouni ,&nbsp;Fatma Ayedi ,&nbsp;Zouheir Sahnoun ,&nbsp;Tarek Rebai","doi":"10.1016/j.biopha.2025.118112","DOIUrl":"10.1016/j.biopha.2025.118112","url":null,"abstract":"<div><div>We were interested in this work to make a comparison between the protective effect of the ethanolic extract of <em>Urtica urens</em> L. (UU) and the effect of the bisphosphonate (BP) against osteoporosis induced in rats by intraperitoneal (IP) and oral (gavage) administration. The female rats were ovariectomized to cause osteoporosis. Several biological, histological, and histomorphometric analyses were used to study bone development. The results indicate that the EtOH extract of UU has a positive effect against osteoporosis for both routes of administration (IP and gavage). This effect could be attributed to the high richness of UU leaves in flavonoids, polyphenols, vitamins (vitamin D), and minerals (Ca and P). UU and BP have a histology score at 4 after 12 weeks of ovariectomy and for 60 days. Biological, histological, and histomorphometric studies have shown that UU and BP have significantly similar effects on the treatment of osteoporosis with both routes of administration. This plant could have a lower affinity than BP, possibly related to the dose. On the other hand, we concluded that IP administration is better than oral administration.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118112"},"PeriodicalIF":6.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912050","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}
引用次数: 0
Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor? 妊娠期四氢大麻酚暴露扰乱记忆受损青少年后代的海马线粒体呼吸:线粒体CB1受体是否有作用?
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2025-05-07 DOI: 10.1016/j.biopha.2025.118144
Gianluca Lavanco , Valentina Castelli , Cesare D’Amico , Francesca Vaccaro , Giuseppe Tringali , Maria Elisabetta Clementi , Patrizia Bottoni , Martin Kuchar , Petr Palivec , Olivia Engmann , Anna Brancato , Carla Cannizzaro
{"title":"Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor?","authors":"Gianluca Lavanco ,&nbsp;Valentina Castelli ,&nbsp;Cesare D’Amico ,&nbsp;Francesca Vaccaro ,&nbsp;Giuseppe Tringali ,&nbsp;Maria Elisabetta Clementi ,&nbsp;Patrizia Bottoni ,&nbsp;Martin Kuchar ,&nbsp;Petr Palivec ,&nbsp;Olivia Engmann ,&nbsp;Anna Brancato ,&nbsp;Carla Cannizzaro","doi":"10.1016/j.biopha.2025.118144","DOIUrl":"10.1016/j.biopha.2025.118144","url":null,"abstract":"<div><div>Mitochondria are central to cellular energy metabolism, contributing to synaptic transmission and plasticity. The mitochondrial membranes present the cannabinoid type-1 receptor (mito-CB1R), which has been functionally linked to neuronal energy supply and cognitive processing. Prenatal exposure to Δ9-tetrahydrocannabinol (pTHC) has been associated with cognitive impairments associated with molecular cellular and functional abnormalities in several brain regions, including the hippocampus. This study aims at assessing whether, besides the memory impairment, pTHC exposure may result in mitochondrial molecular and functional alterations in the hippocampus of the offspring. Moreover, the assessment of CB1R expression is also carried out as a proxy of CB1 signalling in pTHC-exposed offspring. THC (2 mg/Kg), or vehicle, was administered to the dams from gestational day (GD) 5 to GD20, and the offspring were tested for declarative memory using the Novel Object Recognition test in the L-maze. We also assessed: mitochondrial respiration by high-resolution respirometry; mitochondrial respiratory complex-I subunit NDUFS1 protein levels, and mito-CB1R expression by ELISA. Our results revealed: significant memory impairment in pTHC-exposed offspring; attenuated mitochondrial respiration in the hippocampus alongside a marked reduction in complex-I-subunit NDUFS1; a significant increase in mito-CB1R expression. This is the first evidence of pTHC exposure-induced impairment in memory processing in the offspring that suggests a functional link between an attenuation in mitochondrial bioenergetics and abnormal CB1R signalling in the hippocampus.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"187 ","pages":"Article 118144"},"PeriodicalIF":6.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916631","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}
引用次数: 0
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