Acta Pharmaceutica Sinica. B最新文献_第6页

Biomimetic liposomes synergize with high-intensity focused ultrasound to induce ferroptosis in tumors 仿生脂质体与高强度聚焦超声协同作用诱导肿瘤铁下垂

1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 DOI: 10.1016/j.apsb.2026.02.024

Ruizhe Xu, Xuejing Li, Xiaomin Su, Xifeng Qin, Ying He, Siyu Wang, Yue Liu (292931), Jiayi Wu, Ting Wang, Mingyang Liu, Boshu Ouyang, Jia Li (160557), Wuli Yang, Bo Zhang, Hei Chen

{"title":"Biomimetic liposomes synergize with high-intensity focused ultrasound to induce ferroptosis in tumors","authors":"Ruizhe Xu, Xuejing Li, Xiaomin Su, Xifeng Qin, Ying He, Siyu Wang, Yue Liu (292931), Jiayi Wu, Ting Wang, Mingyang Liu, Boshu Ouyang, Jia Li (160557), Wuli Yang, Bo Zhang, Hei Chen","doi":"10.1016/j.apsb.2026.02.024","DOIUrl":"https://doi.org/10.1016/j.apsb.2026.02.024","url":null,"abstract":"The efficient targeted delivery and on-demand release of nanomedicines still present significant challenges in tumor therapy. In the present study, we developed a novel strategy of tumor ferroptosis therapy through the synergistic effect of nanomedicines (biomimetic liposomes) and a medical device (high-intensity focused ultrasound, HIFU). It was found that HIFU irradiation induced heightened expressions of CD44 and reactive oxygen species (ROS) in tumor cells by 1.43-fold and 2.64-fold, respectively. This allowed the gambogic acid-loaded, platelet-mimicking liposomes (PLip) to more precisely target the tumor cells through the interaction of CD44 and P-selectin on the PLip and subsequently ROS-responsively release the drug from PLip, thus effectively killing tumor cells. Crucially, gambogic acid also significantly enhanced ROS production, leading to lipid peroxidation and augmented ferroptosis induced by HIFU. In summary, HIFU demonstrates immense potential in synergizing with nanomedicines to combat tumors. HIFU upregulated CD44 and ROS, enabling platelet-mimicking liposomes to target tumors and release gambogic acid, enhancing lipid peroxidation and ferroptosis, demonstrating synergistic nanomedicine-device tumor therapy potential.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of PGK1 enhances sensitivity to tyrosine kinase inhibitor in T315I-mutant leukemia 抑制PGK1增强t315i突变白血病对酪氨酸激酶抑制剂的敏感性

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 10.1016/j.apsb.2025.12.039

Huijing Wang , Fengyu Jiang , An Pan , Chenlong Jin , Yangyang Xue , Wenjie Liu , Renjun Gu , Yanyu Zhou , Qiuhong Shen , Tonghui Ma , Xiaoxuan Yu

{"title":"Inhibition of PGK1 enhances sensitivity to tyrosine kinase inhibitor in T315I-mutant leukemia","authors":"Huijing Wang , Fengyu Jiang , An Pan , Chenlong Jin , Yangyang Xue , Wenjie Liu , Renjun Gu , Yanyu Zhou , Qiuhong Shen , Tonghui Ma , Xiaoxuan Yu","doi":"10.1016/j.apsb.2025.12.039","DOIUrl":"10.1016/j.apsb.2025.12.039","url":null,"abstract":"<div><div>Phosphoglycerate kinase 1 (PGK1) is traditionally recognized for its pivotal role in glycolysis. Our findings reveal that PGK1 also functions as a protein kinase phosphorylating valosin-containing protein (VCP) at S746, which subsequently reduces Beclin 1 deubiquitination and impairs autophagy. Inhibition of PGK1 initiates autophagy in T315I-mutant chronic myeloid leukemia (CML) cells, thereby enhancing their sensitivity to first-generation Tyrosine Kinase Inhibitor (TKI) imatinib and third-generation TKI ponatinib. Despite the significant clinical implications, few PGK1-targeting inhibitors have been approved for clinical use to date. Through a comprehensive high-throughput screening of ∼20,000 natural compounds, we identified flavonoid as potent inhibitors of the enzymatic activity of PGK1. Subsequent structural optimization of these flavonoid derivatives led to the development of CPU-216, a compound that binds to the GLU344 and PHE292 residues of PGK1, effectively inhibiting its enzymatic and kinase activity. Notably, CPU-216 induces autophagy <em>via</em> VCP and Beclin 1 in CML-T315I cells, enhancing their responsiveness to TKIs. These discoveries propose a novel therapeutic strategy for T315I-mutant CML, underscoring the potential to develop targeted treatments that leverage the kinase functions of PGK1.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1449-1465"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553427","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

Cover Story 封面故事

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2026-03-20 DOI: 10.1016/S2211-3835(26)00067-5

引用次数: 0

Aptamers targeting respiratory syncytial virus showed high inhibitory activity by blocking the G protein 以呼吸道合胞病毒为靶点的适体通过阻断G蛋白表现出较高的抑制活性

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.apsb.2025.12.027

Ge Yang , Guangyu Jiang , Xintao Lian , Boming Cui , Shuo Wu , Huiqiang Wang , Haiyan Yan , Kun Wang , Rongmei Gao , Feng Qu , Jiandong Jiang , Yuhuan Li

引用次数: 0

Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy 胶质母细胞瘤的靶向免疫抑制网络：克服免疫缺陷和提高治疗效果的新策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.apsb.2026.01.015

Songlei Zhou , Xiaokun Zhang , Jiayi Lin , Fenfen Ma , Hongzhuan Chen , Jun Chen , Xin Luan

{"title":"Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy","authors":"Songlei Zhou , Xiaokun Zhang , Jiayi Lin , Fenfen Ma , Hongzhuan Chen , Jun Chen , Xin Luan","doi":"10.1016/j.apsb.2026.01.015","DOIUrl":"10.1016/j.apsb.2026.01.015","url":null,"abstract":"<div><div>Glioblastoma (GBM), the most aggressive primary brain tumor, remains a formidable therapeutic challenge, with a median survival under 15 months. Despite the current standard of care-comprising maximal safe surgical resection, radiotherapy, and temozolomide chemotherapy-patient outcomes have seen minimal improvement over the past two decades. A key barrier to effective treatment is GBM’s robust and multifaceted immunosuppressive network, which critically undermines antitumor immunity. While much of the research has focused on the local immunosuppressive tumor microenvironment, systemic immunosuppression represents an equally important yet often underappreciated obstacle, significantly impairing host immune competence. Effective immunotherapy relies on an intact and functional immune system capable of mounting durable T cell-mediated responses. However, GBM induces profound systemic immune dysfunction, manifested by severe lymphopenia and depletion of effector immune cells, which further limits immune-mediated tumor control. Therefore, a comprehensive understanding of both systemic and local immunosuppressive mechanisms is essential for the rational design of effective immunotherapeutic strategies. In this review, we examine the unique physiological features of the brain, dissect the immunosuppressive landscape of GBM at both local and systemic levels, and highlight recent insights into the underlying mechanisms. We also discuss current immunotherapeutic modalities, and emerging drug delivery strategies aimed at overcoming immunosuppression to improve therapeutic efficacy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1272-1291"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553435","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

Liposomal simvastatin potentiates intranasal H1N1 influenza subunit vaccine via increasing transcytosis of antigen and submucosal dendritic cell recruitment 辛伐他汀脂质体通过增加抗原的胞吞作用和粘膜下树突状细胞募集来增强鼻内H1N1流感亚单位疫苗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2026-01-05 DOI: 10.1016/j.apsb.2025.12.021

Afeng Yang , Chen Zhang , Aihua Wu , Jiaojiao Xu , Hongzheng Lin , Zhe Li , Tingting Li , Yunlu Li , Ningshao Xia , Xunlong Shi , Tianying Zhang , Wei Lu

{"title":"Liposomal simvastatin potentiates intranasal H1N1 influenza subunit vaccine via increasing transcytosis of antigen and submucosal dendritic cell recruitment","authors":"Afeng Yang , Chen Zhang , Aihua Wu , Jiaojiao Xu , Hongzheng Lin , Zhe Li , Tingting Li , Yunlu Li , Ningshao Xia , Xunlong Shi , Tianying Zhang , Wei Lu","doi":"10.1016/j.apsb.2025.12.021","DOIUrl":"10.1016/j.apsb.2025.12.021","url":null,"abstract":"<div><div>Intranasal vaccines specifically eliciting mucosal immunity in the upper respiratory tract have shown advantages in protecting against respiratory virus invasion. Yet, no clinically licensed intranasal adjuvant remains a major hurdle for the development of intranasal vaccines with low immunogenic antigens like subunit vaccines. Here, we show that liposomes loading simvastatin (Lipo-SV) serve as potent mucosal adjuvants for the intranasal liposomal subunit vaccine encapsulating the hemagglutinin 1 (HA1) glycoprotein of A/PR/8/34 (PR8) H1N1 influenza (Lipo-HA1), providing robust protection against the lethal PR8 H1N1 infection. Compared to cholera toxin subunit B (CTB), the only mucosal adjuvant used in humans, the Lipo-SV substantiate intranasal Lipo-HA1 vaccines to elicit robust systemic and local mucosal immune responses. The underlying mechanism of the adjuvanticity of Lipo-SV involves the increased transcytosis of antigens by inhibiting the geranylgeranylation of RAB5 and RAB7B GTPases in nasal epithelial cells. Moreover, Lipo-SV enhance the submucosal recruitment of dendritic cell for antigen uptake <em>via</em> the Toll-like receptor 4-dependent pathway. Unlike CTB, intranasal Lipo-SV do not induce inflammation in the lung or the inflammatory cytokines in the central nervous system. Our results present a paradigm of design of mucosal adjuvant to target the mucosal epithelial cells in addition to the antigen-presenting cells.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1625-1642"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553401","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

Multi-omics-based identification of METTL11B as a novel biomarker in esophageal squamous cell carcinoma METTL11B作为食管鳞状细胞癌新生物标志物的多组学鉴定

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI: 10.1016/j.apsb.2026.01.025

Wenke Jin , Hongyao Li , Yanmei Chen , Wei Wang , Rui Liu , Ning Li , Yong Yuan

引用次数: 0

Single-cell RNA sequencing-guided drug discovery to alleviate radiotherapy-induced esophageal toxicity 单细胞RNA测序引导药物发现以减轻放疗引起的食道毒性

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2025-12-27 DOI: 10.1016/j.apsb.2025.12.038

Wenling Tu , Hangfeng Liu , Hongyu Lin , Jinkang Zhang , Tang Feng , Zhenyu Ding , Qing Li , Yuhong Shi , Zehua Zhou , Shuyu Zhang

引用次数: 0

bHLH130 mediates gibberellin signaling to regulate tanshinone biosynthesis in Salvia miltiorrhiza bHLH130介导赤霉素信号通路调控丹参酮的合成

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2025-12-03 DOI: 10.1016/j.apsb.2025.11.041

Haizheng Yu , Ruiyang Yao , Sixue Zhang , Yongxing Chen , Caiyan Liang , Yijing Liu , Wenrui Li , Bingcong Xing , Dongfeng Yang , Lei Zhang

{"title":"bHLH130 mediates gibberellin signaling to regulate tanshinone biosynthesis in Salvia miltiorrhiza","authors":"Haizheng Yu , Ruiyang Yao , Sixue Zhang , Yongxing Chen , Caiyan Liang , Yijing Liu , Wenrui Li , Bingcong Xing , Dongfeng Yang , Lei Zhang","doi":"10.1016/j.apsb.2025.11.041","DOIUrl":"10.1016/j.apsb.2025.11.041","url":null,"abstract":"<div><div><em>Salvia miltiorrhiza</em> is a prominent traditional Chinese medicinal (TCM) herb with notable therapeutic applications, especially in treatment of cardiovascular and cerebrovascular diseases. A crucial role in promoting tanshinone biosynthesis is attributed to the gibberellic acid (GA) signaling pathway; however, its precise regulatory mechanisms remain incompletely understood. In the current investigation, we identified bHLH130, a GA-responsive bHLH transcription factor (TF), <em>via</em> transcriptomic analysis of GA-treated hairy roots from <em>S. miltiorrhiza</em>. Functional analysis demonstrated that <em>bHLH130</em> overexpression markedly suppressed tanshinone biosynthesis, whereas its knockout resulted in elevated tanshinone accumulation. Additionally, it was confirmed that bHLH130 directly targets E-box motifs within the promoters of biosynthetic genes, including <em>DXS2</em>, <em>CPS1</em>, <em>KSL1</em>, and <em>CYP76AH1</em>, thereby negatively regulating their transcriptional activities. Moreover, bHLH130 interacts with DELLA4, forming a regulatory complex implicated in the modulation of tanshinone biosynthesis. Co-overexpression assays revealed that <em>DELLA4</em> attenuated the inhibitory effects of <em>bHLH130</em> on tanshinone accumulation. Collectively, our data propose that the bHLH130‒DELLA4 interaction constitutes a critical regulatory node, balancing GA signaling with secondary metabolite production and offering novel strategies for the metabolic engineering of tanshinones. In conclusion, this research delineates the regulatory role of bHLH130 in tanshinone synthesis, providing valuable insights into the GA-mediated modulation of secondary metabolism.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1747-1761"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553538","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

Liver–pancreas communication in disease and drug development 肝脏-胰腺在疾病和药物开发中的沟通

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.apsb.2026.01.018

Yan Jia , Qingtian Zhu , Qiong Pan , Guotao Lu , Jia Xiao

{"title":"Liver–pancreas communication in disease and drug development","authors":"Yan Jia , Qingtian Zhu , Qiong Pan , Guotao Lu , Jia Xiao","doi":"10.1016/j.apsb.2026.01.018","DOIUrl":"10.1016/j.apsb.2026.01.018","url":null,"abstract":"<div><div>The liver and pancreas are metabolically intertwined organs whose bidirectional communication is critical for maintaining systemic homeostasis. Dysregulation of this inter-organ crosstalk is a central driver in the pathology of a growing list of prevalent diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), liver cancer, acute and chronic pancreatitis, and various forms of diabetes. Given the substantial global health burden of these conditions and the lack of effective, Food and Drug Administration (FDA)-approved pharmacological interventions for those diseases, understanding the intricate mechanisms is an urgent and timely endeavor. This review provides a comprehensive synthesis of recent advancements in deciphering the molecular basis of liver–pancreas communication. We explore the multifaceted signaling networks involved, including the roles of liver-derived hepatokines, pancreas-derived hormones, extracellular vesicles, and metabolic exchanges. This axis is further integrated within broader systemic networks involving the gut, neuronal system, adipose tissue, and skeletal muscle. While clinical trials targeting this communication show promise (<em>e.g.</em>, FGF21- and bile acid-related drugs), significant challenges remain, particularly the lack of FDA-approved pharmacological treatments for alcohol-associated liver disease (ALD), and acute/chronic pancreatitis. Future research must elucidate specific signaling pathways, identify novel pancreas-derived factors, and develop innovative therapeutic strategies. In particular, small molecule drug discovery based on polypharmacology, for these complex metabolic and organ-specific diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 3","pages":"Pages 1250-1271"},"PeriodicalIF":14.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147553437","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