Acta Pharmaceutica Sinica. B最新文献_第3页

High intensity forced ultrasound-driven ferroptosis as a strategy for anti-tumor immune priming 高强度强迫超声驱动铁下垂作为抗肿瘤免疫启动的策略

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.006

Xuejing Li , Jiayi Wu , Ruizhe Xu , Xifeng Qin , Siyu Wang , Wuli Yang , Zhiqing Pang

{"title":"High intensity forced ultrasound-driven ferroptosis as a strategy for anti-tumor immune priming","authors":"Xuejing Li , Jiayi Wu , Ruizhe Xu , Xifeng Qin , Siyu Wang , Wuli Yang , Zhiqing Pang","doi":"10.1016/j.apsb.2025.05.006","DOIUrl":"10.1016/j.apsb.2025.05.006","url":null,"abstract":"<div><div>Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3788-3804"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Artificial intelligence and anti-cancer drugs' response 人工智能和抗癌药物的反应

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.009

Xinrui Long , Kai Sun , Sicen Lai , Yuancheng Liu , Juan Su , Wangqing Chen , Ruhan Liu , Xiaoyu He , Shuang Zhao , Kai Huang

{"title":"Artificial intelligence and anti-cancer drugs' response","authors":"Xinrui Long , Kai Sun , Sicen Lai , Yuancheng Liu , Juan Su , Wangqing Chen , Ruhan Liu , Xiaoyu He , Shuang Zhao , Kai Huang","doi":"10.1016/j.apsb.2025.05.009","DOIUrl":"10.1016/j.apsb.2025.05.009","url":null,"abstract":"<div><div>Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3355-3371"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Polymer-assisted PD-L1 degradation and targeted photodynamic therapy synergize to suppress immunodeficient tumors 聚合物辅助PD-L1降解和靶向光动力治疗协同抑制免疫缺陷肿瘤

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.022

Changyong Guo , Shipeng He , Huaxing Shen, Wei Cong, Jinqiu Li, Yajing Ji, Wenjing Huang, Fei Gao, Honggang Hu

{"title":"Polymer-assisted PD-L1 degradation and targeted photodynamic therapy synergize to suppress immunodeficient tumors","authors":"Changyong Guo , Shipeng He , Huaxing Shen, Wei Cong, Jinqiu Li, Yajing Ji, Wenjing Huang, Fei Gao, Honggang Hu","doi":"10.1016/j.apsb.2025.05.022","DOIUrl":"10.1016/j.apsb.2025.05.022","url":null,"abstract":"<div><div>Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in “cold” tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable <em>N</em>-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3805-3818"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Unraveling the therapeutic landscape of approved non-peptide macrocycles 揭示被批准的非肽大环的治疗前景

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.021

Zhonghua Li , Zhenqiang Zhang , Bin Yu

引用次数: 0

Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection 细胞质和核NFATc3共同参与血管平滑肌细胞功能障碍，驱动主动脉瘤和夹层

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.016

Xiu Liu , Li Zhao , Deshen Liu , Lingna Zhao , Yonghua Tuo , Qinbao Peng , Fangze Huang , Zhengkun Song , Chuanjie Niu , Xiaoxia He , Yu Xu , Jun Wan , Peng Zhu , Zhengyang Jian , Jiawei Guo , Yingying Liu , Jun Lu , Sijia Liang , Shaoyi Zheng

{"title":"Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection","authors":"Xiu Liu , Li Zhao , Deshen Liu , Lingna Zhao , Yonghua Tuo , Qinbao Peng , Fangze Huang , Zhengkun Song , Chuanjie Niu , Xiaoxia He , Yu Xu , Jun Wan , Peng Zhu , Zhengyang Jian , Jiawei Guo , Yingying Liu , Jun Lu , Sijia Liang , Shaoyi Zheng","doi":"10.1016/j.apsb.2025.05.016","DOIUrl":"10.1016/j.apsb.2025.05.016","url":null,"abstract":"<div><div>This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC–NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC–NFATc3 overexpression. VSMC–NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine—targets eEF2 and inhibits protein synthesis—inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC–NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3663-3684"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma 利格列汀与cPLA2抑制协同作用，通过阻断dpp4介导的胶质瘤EGFR稳定来增强替莫唑胺的疗效

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.012

Dongyuan Su , Biao Hong , Shixue Yang , Jixing Zhao , Xiaoteng Cui , Qi Zhan , Kaikai Yi , Yanping Huang , Jiasheng Ju , Eryan Yang , Qixue Wang , Junhu Zhou , Yunfei Wang , Xing Liu , Chunsheng Kang

{"title":"Linagliptin synergizes with cPLA2 inhibition to enhance temozolomide efficacy by interrupting DPP4-mediated EGFR stabilization in glioma","authors":"Dongyuan Su , Biao Hong , Shixue Yang , Jixing Zhao , Xiaoteng Cui , Qi Zhan , Kaikai Yi , Yanping Huang , Jiasheng Ju , Eryan Yang , Qixue Wang , Junhu Zhou , Yunfei Wang , Xing Liu , Chunsheng Kang","doi":"10.1016/j.apsb.2025.05.012","DOIUrl":"10.1016/j.apsb.2025.05.012","url":null,"abstract":"<div><div>The polymerase 1 and transcript release factor (PTRF)–cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF–cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent <em>in vivo</em> investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4–EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3632-3645"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Antisense oligonucleotides targeting IRF4 alleviate psoriasis 针对IRF4的反义寡核苷酸可缓解银屑病

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.004

Yanxia Yu , Yirui Wang , Weiwei Chen , Chang Zhang , Zhuo li , Jing Yu , Minhao Wang , Can Song , Sihao Yan , Jiayi Lu , Liangdan Sun

{"title":"Antisense oligonucleotides targeting IRF4 alleviate psoriasis","authors":"Yanxia Yu , Yirui Wang , Weiwei Chen , Chang Zhang , Zhuo li , Jing Yu , Minhao Wang , Can Song , Sihao Yan , Jiayi Lu , Liangdan Sun","doi":"10.1016/j.apsb.2025.05.004","DOIUrl":"10.1016/j.apsb.2025.05.004","url":null,"abstract":"<div><div>Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4<sup>+</sup> (CD4<sup>+</sup>) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1<em>β</em>. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-<em>γ</em>t (ROR<em>γ</em>t) and increasing the secretion of IL-17A, thereby establishing the IL-1<em>β</em>/IL-23A–IRF4–EP300–<em>RORC</em>–IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a <em>Irf4</em><sup><em>−/−</em></sup> gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for <em>Irf4</em>. This amelioration was accompanied by a decreased number of IL-17A-producing CD4<sup>+</sup> T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3575-3590"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Non-blocking anti-PD-L1 nanobody conjugated to TLR7 agonist mediates macrophage/NK cell-associated antitumor effects 结合TLR7激动剂的非阻断抗pd - l1纳米体介导巨噬细胞/NK细胞相关的抗肿瘤作用

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.005

Chao Hu , Chen Chen , Xiaolu Yu , Zhiying Li , Feng Tang , Qi Sun , Yiru Long , Likun Gong

引用次数: 0

Nanomedicine-induced pyroptosis for anti-tumor immunotherapy: Mechanism analysis and application prospects 纳米药物诱导焦亡抗肿瘤免疫治疗：机制分析及应用前景

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.021

Yuelin Huang , Chunting Wang , Yanhong Chen , Dengbin Wang , Defan Yao

引用次数: 0

Cover Story 封面故事

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/S2211-3835(25)00387-9

引用次数: 0