Biochemical pharmacology最新文献

{"title":"Serum-derived extracellular vesicles mediate acquired multidrug resistance of MCF-7 breast cancer cells induced by chemotherapeutic drugs","authors":"Mi Zhou ,&nbsp;Jiahuan Hong ,&nbsp;Xiaofeng Qiu ,&nbsp;Zixian Xiong ,&nbsp;Xiaoyong Liu ,&nbsp;Zhuan Qin ,&nbsp;Zhesi Luo ,&nbsp;Qi Chen ,&nbsp;Mianjie Lin ,&nbsp;Ling Min ,&nbsp;Xiaorong Yang ,&nbsp;Xinmin Guo ,&nbsp;Bin Xu ,&nbsp;Jianwen Mao","doi":"10.1016/j.bcp.2025.116923","DOIUrl":"10.1016/j.bcp.2025.116923","url":null,"abstract":"<div><div>Multidrug resistance (MDR) in tumor cells presents a significant challenge in cancer therapy. This study investigates the role of serum-derived extracellular vesicles (EVs) in mediating MDR during chemotherapeutic exposure. The findings indicate that short- or long-term co-incubation of doxorubicin (Dox)-pretreated serum derived EVs (EVs(S-PT)) caused drug-sensitive MCF-7 breast cancer cells to develop a MDR phenotype. In addition, serum EVs contain a high concentration of unglycosylated P-glycoprotein (P-gp). Chemotherapy treatment of tumor patients or exposure to chemotherapeutic drugs in vitro activates serum glycosyltransferases, inducing glycosylation of EVs P-gp and giving it drug-pumping activity. Furthermore, damage caused by Dox to the vascular endothelial barrier facilitates the crossing of serum EVs into the tumor microenvironment. These EVs are then taken up by tumor cells, providing them with access to a significant quantity of glycosylated P-gp proteins that possess transporter activity and the ability to evade degradation by the ubiquitin proteasome system. The results indicate that EVs(S-PT) transfers glycosylated P-gp across the damaged vascular endothelial barrier into MCF-7 cells and that these glycosylated P-gp remain intracellular for a long period of time, inducing MDR in the cells. Our study highlights a novel mechanism of acquired MDR and provides a potential avenue for therapeutic interventions targeting the serum EVs pathway in cancer therapy.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116923"},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800488","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":"A novel IgD-FcδR blocker, IgD-Fc-Ig fusion protein, effectively alleviates abnormal activation of T cells the disease progression in systemic lupus erythematosus","authors":"Jingjing He ,&nbsp;Danyan Liu ,&nbsp;Li Jiang ,&nbsp;Mengqin Chen ,&nbsp;Xi Ling ,&nbsp;Manling Dong ,&nbsp;Tiantian Wu ,&nbsp;Tingting Guo ,&nbsp;Nuo Xu ,&nbsp;Jing Zhang ,&nbsp;Tao Li ,&nbsp;Yueye Wang ,&nbsp;Jiemin Zhao ,&nbsp;Wei Wei ,&nbsp;Shangxue Yan ,&nbsp;Yujing Wu","doi":"10.1016/j.bcp.2025.116930","DOIUrl":"10.1016/j.bcp.2025.116930","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease with complex pathogenesis and unclear causes. Elevated levels of IgD have been observed in the peripheral blood of SLE patients, suggesting a potential role for IgD through its interaction with the IgD Fc receptor (FcδR). This study aimed to explore the impact of IgD on T cell function in SLE and evaluate the therapeutic potential of targeting the IgD-FcδR pathway using an IgD-Fc-Ig fusion protein. In SLE patients, biomarkers such as BAFF, ESR, anti-dsDNA and SLEDAI-2k, which are used to assess disease activity and clinical presentations, were significantly correlated with sIgD levels. As an IgD-FcδR blocker, IgD-Fc-Ig effectively suppressed the activation and proliferation of CD4⁺ T cells stimulated by IgD, restored the balance between Th17 and Treg cell subsets, and reduced the expression and interaction of phosphorylated Lck (p-Lck) and JAK2 (p-JAK2). Moreover, <em>in vivo</em> study demonstrated that IgD-Fc-Ig may also ameliorates disease manifestations in MRL/lpr mice with lupus nephritis. IgD-Fc-Ig could reduce serum IgD levels, proteinuria level and the kidney deposition of immune complex C3, ameliorate histopathological changes in kidney and spleen tissue. Additionally, it reversed the state of excessive activation and imbalance of Th17/Treg cell subsets, reduced cytokine levels, and downregulated p-JAK2 and p-STAT3 expression. In conclusion, our study revealed a correlation between abnormally increased sIgD and SLE pathogenesis, IgD-FcδR-Lck-JAK2-STAT3 may act as an important mechanism contributing to T cell activation in SLE. IgD-Fc-Ig fusion protein may represent a promising targeted therapy for SLE.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116930"},"PeriodicalIF":5.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802205","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":"Scutellarein ameliorates pulmonary arterial hypertension via sirtuin 1 mediated deacetylation of nicotinamide nucleotide transhydrogenase","authors":"Heng Tang ,&nbsp;Ke Ning ,&nbsp;Boji Wu ,&nbsp;Xuhong Wang ,&nbsp;Jingyu He ,&nbsp;Pingping Li ,&nbsp;Lina Pan ,&nbsp;Jiawen Zhang ,&nbsp;Yi He ,&nbsp;Shizhu Bian ,&nbsp;Xingyu Ma ,&nbsp;Jihang Zhang ,&nbsp;Chuan Liu ,&nbsp;Zhexue Qin ,&nbsp;Houyuan Hu","doi":"10.1016/j.bcp.2025.116932","DOIUrl":"10.1016/j.bcp.2025.116932","url":null,"abstract":"<div><div>Scutellarein (Sc), a natural flavonoid, holds potential for treating pulmonary arterial hypertension (PAH), yet its mechanisms remain unexplored. This study investigated Sc’s therapeutic effects and underlying pathways in PAH. In vivo experiments demonstrated that Sc significantly attenuated right ventricular hypertension, pulmonary arterial remodeling, αSMA expression, and vascular inflammation in PAH models. In vitro, Sc suppressed hypoxia-induced proliferation, migration, inflammation, and pyroptosis in human pulmonary artery smooth muscle cells (HPASMCs). Mechanistically, Sc activated the SIRT1/NAD⁺ axis to restore mitochondrial homeostasis: it upregulated SIRT1 expression and elevated NAD⁺ levels by promoting SIRT1-mediated deacetylation of nicotinamide nucleotide transhydrogenase (NNT), thereby enhancing NNT activity. Elevated NAD⁺ further activated SIRT1, forming a self-reinforcing SIRT1/NNT/NAD⁺ feedback loop that mitigated hypoxia-induced mitochondrial dysfunction. This study identifies Sc as a novel regulator of the SIRT1-dependent NNT deacetylation pathway, which stabilizes NAD⁺ homeostasis to counteract HPASMCs dysregulation in PAH. These findings highlight Sc’s potential as a therapeutic candidate for PAH, offering insights into targeting mitochondrial-metabolic pathways for vascular remodeling diseases.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116932"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794641","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":"Insights into 2D and 3D cell culture models for nanoparticle-based drug delivery to glioblastoma","authors":"Girstautė Dabkevičiūtė ,&nbsp;Vilma Petrikaitė","doi":"10.1016/j.bcp.2025.116931","DOIUrl":"10.1016/j.bcp.2025.116931","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains a formidable challenge due to its aggressive nature, protected location within the brain, and resistance to conventional treatments. Its complex tumor microenvironment (TME), coupled with the blood–brain barrier (BBB), hinders drug delivery leading to poor treatment outcomes. Nanoparticles (NPs) offer a promising solution, as they can improve the pharmacokinetic properties of anticancer agents. By functionalizing NPs with targeting molecules, researchers aim to enhance drug concentration in the brain. However, developing effective NP-based therapies requires robust in vitro models that accurately capture the complexities of GBM.</div><div>Two-dimensional (2D) and three-dimensional (3D) cell culture models provide a versatile platform for studying NP-cell interactions. By customizing cell types, incorporating TME components, and adjusting flow conditions, researchers can tailor these models to specific research questions. While 2D models offer a simpler starting point, 3D models, such as multicellular spheroids and organoids, can more accurately replicate the complex TME, including the BBB and tumor heterogeneity. These models enable a more comprehensive evaluation of NP efficacy and safety, ultimately accelerating drug development and reducing reliance on animal testing.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116931"},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787639","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":"NUF2 activated by YY1 promotes prostate cancer malignancy via p38/MAPK signaling axis and serves as a therapeutic target","authors":"Chengqi Jin ,&nbsp;Jing Xu ,&nbsp;Wentao Luo ,&nbsp;Hanxu Guo ,&nbsp;Li Ding ,&nbsp;Yongqiang Liu ,&nbsp;Ji Liu ,&nbsp;Libin Zou ,&nbsp;Yang Yu ,&nbsp;Yajuan Hao ,&nbsp;Bin Yang","doi":"10.1016/j.bcp.2025.116919","DOIUrl":"10.1016/j.bcp.2025.116919","url":null,"abstract":"<div><div>Prostate cancer (PCa) is one of the most prevalent malignancies in the male urogenital system. Despite extensive research into its mechanisms of initiation and progression, the full scope of its pathophysiology remains insufficiently understood. This study demonstrated that NUF2 was significantly overexpressed in PCa, with its elevated levels correlating with poor patient survival outcomes. Silencing NUF2 notably impaired PCa cell proliferation and metastasis in both in vitro and in vivo models, whereas its overexpression promoted these processes. Additionally, YY1 was identified as a direct transcriptional activator of NUF2, binding to its promoter and enhancing its oncogenic effects through activation of downstream targets. Moreover, NUF2 promoted PCa progression by recruiting p38, accelerating its phosphorylation, and activating the p38/MAPK signaling pathway. Through the PubChem database, fisetin was identified as a small molecule inhibitor of NUF2. Fisetin effectively inhibited PCa cell proliferation, and NUF2 overexpression reversed this inhibitory effect. In conclusion, our results suggest that NUF2 overexpression accelerated PCa progression via the p38/MAPK pathway, regulated by YY1. The identification of fisetin as a NUF2 inhibitor offers a promising therapeutic strategy for targeting NUF2 to impede PCa growth. NUF2 may thus serve as a valuable prognostic biomarker and a potential therapeutic target for PCa.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116919"},"PeriodicalIF":5.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787641","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":"Vascular cellular senescence in human atherosclerosis: The critical modulating roles of CDKN2A and CDK4/6 signaling pathways","authors":"Guofu Hu ,&nbsp;Haihua Zhou ,&nbsp;Zihui Yuan ,&nbsp;Jian Wang","doi":"10.1016/j.bcp.2025.116916","DOIUrl":"10.1016/j.bcp.2025.116916","url":null,"abstract":"<div><div>Vascular cellular senescence promotes vascular aging and atherogenesis. Mitigating vascular cellular senescence serves as a promising therapy for atherosclerosis. Transcriptomic analysis was conducted to reveal the differentially expressed genes (DEGs) regulating cell proliferation, growth, senescence, and death in human atherosclerotic lesions <em>vs.</em> normal vessels. The key DEGs were screened out using Venn diagrams. Ox-LDL induced umbilical vein endothelial cells (HUVECs) and high fat diet-fed <em>ApoE^-/-</em> mice were utilized to construct model. We identified CDKN2A as a senescence-related DEG. The upregulated CDKN2A depressed the downstream CDK4/6 in ox-LDL treated HUVECs. Ox-LDL aggravated cell-cycle arrest, decreased cellular viability, inhibited migration, led to flattened and enlarged senescent morphology, generated ROS, and elevated β-galactosidase activity along with increment in β-galactosidase expression, which were ameliorated by CDKN2A knockdown and, conversely, were exacerbated by the addition of CDK4/6 inhibitor palbociclib. β-galactosidase activity and ROS production were significantly elevated in human and mice atherosclerotic lesions. β-galactosidase, co-localized with CD31, was obviously upregulated in atherosclerotic lesions, indicating endothelial cellular senescence <em>in vivo</em>. CDKN2A, co-localized with CD31, was markedly increased in atherosclerotic lesions, indicating the CDKN2A immunopositivity in endothelial cells <em>in vivo</em>. Colocalization of CDKN2A with CDK4/6 revealed the potential connection <em>in vivo</em>. Palbociclib exacerbated vascular cell senescence and atherogenesis in mice. Endothelial cellular senescence is present in atherosclerotic lesions. CDKN2A and CDK4/6 pathway is active in endothelial cellular senescence and atherogenesis, and altering CDKN2A and CDK4/6 pathway plays a critical role in alleviating endothelial cellular senescence and atherosclerosis, implying novel targets for prevention of vascular aging and atherogenesis.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116916"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787650","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":"Relevance of transportome among the mechanisms of chemoresistance in hepatoblastoma","authors":"Candela Cives-Losada ,&nbsp;Maitane Asensio ,&nbsp;Oscar Briz ,&nbsp;Luis Miguel Chinchilla-Tábora ,&nbsp;María Manuela Barranco ,&nbsp;Álvaro del Río-Álvarez ,&nbsp;Maria Luz Martinez-Chantar ,&nbsp;Matias A. Avila ,&nbsp;Stefano Cairo ,&nbsp;Carolina Armengol ,&nbsp;Jose J.G. Marin ,&nbsp;Rocio I.R. Macias","doi":"10.1016/j.bcp.2025.116914","DOIUrl":"10.1016/j.bcp.2025.116914","url":null,"abstract":"<div><div>Approximately 20 % of hepatoblastomas (HBs) exhibit a poor response to conventional chemotherapy due to mechanisms of chemoresistance (MOCs), such as reduced intracellular drug accumulation. This study evaluated the role of transportome in the multidrug resistance (MDR) of HB. Paired HB and adjacent liver tissue samples (n = 19) and HB-derived cell lines (HepG2, HuH6) were analyzed for their resistome characterization at mRNA (RT-qPCR, Taqman Low-Density Array, sequencing) and protein (western blot, immunohistochemistry, immunofluorescence) levels. Cell viability (MTT test) proliferation and migration (holographic microscopy) were determined. The impact of short-term (72 h) and long-term (&gt;10 months) exposure of HB cells to cisplatin or doxorubicin on the transportome was investigated. Solute carrier (SLC) family of transporters showed minor relevance in HB MDR, while drug export pumps, particularly MRP2, were associated with poor response to chemotherapy. Exposure of HB cells to doxorubicin or cisplatin up-regulated MDR1, MRP1 and MRP2. In cells with induced persistent chemoresistance, the expression of genes involved in other MOCs, and epigenetic machinery was altered. Chemoresistant cells showed cross-resistance to several anticancer drugs but maintained sensitivity to cabozantinib. In conclusion, drug export pumps, but not SLC uptake transporters, are key contributors to HB chemoresistance. Cabozantinib emerges as a potential therapeutic option for HBs resistant to conventional chemotherapy.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116914"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787646","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":"Characterization of [3H]AZ12464237 as a high affinity, non-nucleotide antagonist radioligand for the P2Y12 receptor","authors":"E. Johanna L. Stéen ,&nbsp;Efthalia-Natalia Tousiaki ,&nbsp;Lee Kingston ,&nbsp;Berend van der Wildt ,&nbsp;Nikolett Lénárt ,&nbsp;Wissam Beaino ,&nbsp;Mariska Verlaan ,&nbsp;Barbara Zarzycka ,&nbsp;Bastian Zinnhardt ,&nbsp;Ádám Dénes ,&nbsp;Luca Gobbi ,&nbsp;Iwan J.P. de Esch ,&nbsp;Charles S. Elmore ,&nbsp;Albert D. Windhorst ,&nbsp;Michael Honer ,&nbsp;Rob Leurs","doi":"10.1016/j.bcp.2025.116900","DOIUrl":"10.1016/j.bcp.2025.116900","url":null,"abstract":"<div><div>The purinergic receptor P2Y₁₂ (P2Y₁₂R) is a well-recognized target for anti-thrombotic agents. This receptor is also expressed in microglia, the main immune cells of the brain, where it modulates microglial activation states and inflammatory responses. To investigate P2Y₁₂R-mediated actions in the central nervous system (CNS), developing novel brain-penetrant ligands and further <em>in vitro</em> studies on brain tissues are essential. A radiolabeled, easily accessible tool compound would significantly advance such drug discovery efforts. Herein, we describe the ³H-labeling of a non-nucleotide P2Y₁₂R antagonist AZ12464237, and its <em>in vitro</em> binding properties to the receptor in membrane preparations from transfected cells, as well as on mouse brain tissues. The radioligand shows high affinity toward both the human and rat P2Y₁₂R, with <em>K_d</em> values of 3.12 ± 0.70 nM (human) and 16.6 ± 3.40 nM (rat), as determined by saturation binding studies. The binding kinetics of [³H]AZ12464237 are rapid with a short target residence time (∼1 min). We further confirmed the selectivity of the radioligand by performing competitive displacement studies, in which reported P2Y₁₂R ligands and other P2Y receptors ligands were tested for binding against [³H]AZ12464237. Additionally, the radioligand proved valuable for <em>in vitro</em> autoradiography studies on mouse brain tissues, although limited off-target binding was observed in P2Y₁₂R knock-out mouse brain. This could be traced to glycogen synthase kinase 3 α. Considering the growing interest in P2Y₁₂R as a biomarker for anti-inflammatory microglia, [³H]AZ12464237 represents a promising tool for <em>in vitro</em> studies, including screening assays aimed at identifying novel P2Y₁₂R ligands for CNS applications.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116900"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778765","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":"CD8+ T cell-based immunotherapy: Promising frontier in human diseases","authors":"Quynh Chau Ton Nu ,&nbsp;Gitima Deka ,&nbsp;Pil-Hoon Park","doi":"10.1016/j.bcp.2025.116909","DOIUrl":"10.1016/j.bcp.2025.116909","url":null,"abstract":"<div><div>The abundant cell components of the adaptive immune system called T lymphocytes (T cells) play important roles in mediating immune responses to eliminate the invaders and create the memory of the germs to form a new immunity for the next encounter. Among them, cytotoxic T cells expressing cell-surface CD8 are the most critical effector cells that directly eradicate the target infected cells by recognizing antigens presented by major histocompatibility complex class I molecules to protect our body from pathological threats. In the continuous evolution of immunotherapy, various CD8⁺ T cell-based therapeutic strategies have been developed based on the role and molecular concept of CD8⁺ T cells. The emergence of such remarkable therapies provides promising hope for multiple human disease treatments such as autoimmunity, infectious disease, cancer, and other non-infectious diseases. In this review, we aim to discuss the current knowledge on the utilization of CD8⁺ T cell-based immunotherapy for the treatment of various diseases, the molecular basis involved, and its limitations. Additionally, we summarize the recent advances in the use of CD8⁺ T cell-based immunotherapy and provide a comprehensive overview of CD8⁺ T cells, including their structure, underlying mechanism of function, and markers associated with CD8⁺ T cell exhaustion. Building upon these foundations, we delineate the advancement of CD8⁺ T cell-based immunotherapies with fundamental operating principles followed by research studies, and challenges, as well as illustrate human diseases involved in this development.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"237 ","pages":"Article 116909"},"PeriodicalIF":5.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778764","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":"A novel way of regression of pregnant corpus luteum during parturition in mice: The ferroptosis associated with NCOA4-mediated ferritinophagy","authors":"Yulu Zhang,&nbsp;Fei Li,&nbsp;Yanmin Cheng,&nbsp;Jun Zhu,&nbsp;Yue Li,&nbsp;Hongru Zhao,&nbsp;Jiahao Song,&nbsp;Jiting Yin,&nbsp;Bei Yang,&nbsp;Haibin Kuang","doi":"10.1016/j.bcp.2025.116910","DOIUrl":"10.1016/j.bcp.2025.116910","url":null,"abstract":"<div><div>Numerous studies have shown that inappropriate regression of corpus luteum would lead to adverse pregnancy outcomes during gestation. However, the detailed mechanisms and types of programmed cell death involved in the regression of pregnant corpus luteum are largely unknown. Here, we investigated whether ferroptosis and ferritinophagy were involved in luteal regression during parturition in mice and related mechanisms. The results showed that ferroptosis and ferritinophagy were both involved in luteal regression during mice <em>peri</em>-parturition <em>in vivo</em>. Erastin (ferroptosis agonist) treatment significantly accelerated luteal regression and induced premature labor in pregnant mice. PGF2α treatment induced the ferroptosis and ferritinophagy of luteal cells in vitro. Nevertheless, inhibition or promotion of ferroptosis significantly altered the states of PGF2α-induced luteal cell viability and ferroptosis. Furthermore, inhibition of autophagy (3-methyladenine co-treatment) alleviated PGF2α-induced ferritinophagy and ferroptosis of luteal cells, and knockdown of NCOA4 reduced the degradation of FTH1 and the level of ferroptosis of luteal cells induced by PGF2α. In summary, our current data demonstrated that the ferroptosis associated with NCOA4-mediated ferritinophagy was a novel way of luteal regression during <em>peri</em>-parturition in mice. Targeting ferroptosis in the corpus luteum may be a therapeutic strategy for preventing luteal insufficiency in the future.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116910"},"PeriodicalIF":5.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759062","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}