Acta Pharmaceutica Sinica. B最新文献_第6页

Leveraging glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) for targeted membrane protein degradation 利用glypican-3 （GPC3）介导的溶酶体靶向嵌合体（GLTACs）靶向膜蛋白降解

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.044

Bin Yu

引用次数: 0

Author correction to “PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism” [Acta Pharm Sin B 13 (2023) 157–173] 作者更正“PRMT6通过触发6PGD/ENO1介导的细胞代谢促进肺癌的致瘤性和顺铂反应”[journal of pharmacy B 13 (2023) 157-173]

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.006

Mingming Sun , Leilei Li , Yujia Niu , Yingzhi Wang , Qi Yan , Fei Xie , Yaya Qiao , Jiaqi Song , Huanran Sun , Zhen Li , Sizhen Lai , Hongkai Chang , Han Zhang , Jiyan Wang , Chenxin Yang , Huifang Zhao , Junzhen Tan , Yanping Li , Shuangping Liu , Bin Lu , Changliang Shan

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GPC3-mediated lysosome-targeting chimeras (GLTACs) for targeted degradation of membrane proteins 靶向降解膜蛋白的gpc3介导溶酶体靶向嵌合体（GLTACs）

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.037

Yuxin Fang , Yaojin Zhu , Wei Wang , Zhewei Xia , Shipeng He , Guoqiang Dong , Chunquan Sheng

{"title":"GPC3-mediated lysosome-targeting chimeras (GLTACs) for targeted degradation of membrane proteins","authors":"Yuxin Fang , Yaojin Zhu , Wei Wang , Zhewei Xia , Shipeng He , Guoqiang Dong , Chunquan Sheng","doi":"10.1016/j.apsb.2025.02.037","DOIUrl":"10.1016/j.apsb.2025.02.037","url":null,"abstract":"<div><div>Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC <strong>WP0</strong> potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2156-2169"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923517","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

Intranodal injection of neoantigen-bearing engineered Lactococcus lactis triggers epitope spreading and systemic tumor regressions 结内注射携带新抗原的工程乳酸乳球菌可引发表位扩散和全身肿瘤消退

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.041

Junmeng Zhu , Yi Sun , Xiaoping Qian , Lin Li , Fangcen Liu , Xiaonan Wang , Yaohua Ke , Jie Shao , Lijing Zhu , Lifeng Wang , Qin Liu , Baorui Liu

{"title":"Intranodal injection of neoantigen-bearing engineered Lactococcus lactis triggers epitope spreading and systemic tumor regressions","authors":"Junmeng Zhu , Yi Sun , Xiaoping Qian , Lin Li , Fangcen Liu , Xiaonan Wang , Yaohua Ke , Jie Shao , Lijing Zhu , Lifeng Wang , Qin Liu , Baorui Liu","doi":"10.1016/j.apsb.2025.02.041","DOIUrl":"10.1016/j.apsb.2025.02.041","url":null,"abstract":"<div><div>Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic <em>Lactococcus lactis</em> (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2217-2236"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923520","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}

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Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer 亚精胺使蛋白酶体失活，增强前列腺癌的铁下垂

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.023

Dan Feng , Jian Zhang , Huanmin Niu , Xiaoxue Zheng , Mengqi Jia , Qiqi Lu , Jing Wang , Wenxue Guo , Qi Sun , Huiqing Yuan , Hongxiang Lou

{"title":"Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer","authors":"Dan Feng , Jian Zhang , Huanmin Niu , Xiaoxue Zheng , Mengqi Jia , Qiqi Lu , Jing Wang , Wenxue Guo , Qi Sun , Huiqing Yuan , Hongxiang Lou","doi":"10.1016/j.apsb.2025.02.023","DOIUrl":"10.1016/j.apsb.2025.02.023","url":null,"abstract":"<div><div>The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe<sup>2+</sup> levels <em>in vitro</em>. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe<sup>2+</sup>, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2095-2113"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923522","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

Overview of host-directed antiviral targets for future research and drug development 展望宿主抗病毒靶点的未来研究和药物开发

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.011

Xiaoxia Gu , Mengzhu Zheng , Ya Gao , Shuang Lin , Xiaotian Zhang , Chunmei Chen , Hucheng Zhu , Weiguang Sun , Yonghui Zhang

{"title":"Overview of host-directed antiviral targets for future research and drug development","authors":"Xiaoxia Gu , Mengzhu Zheng , Ya Gao , Shuang Lin , Xiaotian Zhang , Chunmei Chen , Hucheng Zhu , Weiguang Sun , Yonghui Zhang","doi":"10.1016/j.apsb.2025.03.011","DOIUrl":"10.1016/j.apsb.2025.03.011","url":null,"abstract":"<div><div>Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1723-1751"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924509","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

Construction and application of a large capacity VNAR library from the whitespotted bamboo shark (Chiloscyllium playgiosum) 大容量白斑竹鲨VNAR库的建设与应用

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.012

Hao Li , Litong Liu , Xinyi Kang , Chuan-Wei Chen , Mengran Wang , Shaoqin Fu , Qingtong Zhou , Bo Zhao , Dehua Yang , Ming-Wei Wang

{"title":"Construction and application of a large capacity VNAR library from the whitespotted bamboo shark (Chiloscyllium playgiosum)","authors":"Hao Li , Litong Liu , Xinyi Kang , Chuan-Wei Chen , Mengran Wang , Shaoqin Fu , Qingtong Zhou , Bo Zhao , Dehua Yang , Ming-Wei Wang","doi":"10.1016/j.apsb.2025.02.012","DOIUrl":"10.1016/j.apsb.2025.02.012","url":null,"abstract":"<div><div>Fifty whitespotted bamboo sharks (<em>Chiloscyllium playgiosum</em>) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10<sup>9</sup> colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10<sup>8</sup> CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1912-1921"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923354","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}

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Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk Taxifolin通过肝细胞-星状细胞串扰调节NDRG1在Thr328位点的磷酸化，从而减轻肝纤维化

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.017

Chuan Ding , Zeping Wang , Kao Shi , Sunan Li , Xinyue Dou , Yan Ning , Gang Cheng , Qiao Yang , Xianan Sang , Mengyun Peng , Qiang Lyu , Lu Wang , Xin Han , Gang Cao

{"title":"Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk","authors":"Chuan Ding , Zeping Wang , Kao Shi , Sunan Li , Xinyue Dou , Yan Ning , Gang Cheng , Qiao Yang , Xianan Sang , Mengyun Peng , Qiang Lyu , Lu Wang , Xin Han , Gang Cao","doi":"10.1016/j.apsb.2025.02.017","DOIUrl":"10.1016/j.apsb.2025.02.017","url":null,"abstract":"<div><div>Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) <em>in vivo</em> and <em>in vitro,</em> demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) <em>in vivo</em> and <em>in vitro</em> confirmed that pNDRG1<sub>T328</sub> exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1<sub>T328</sub> in hepatocytes.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2059-2076"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923363","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}

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Author correction to “The neuroprotective effect of traditional Chinese medicinal plants—A critical review” [Acta Pharm Sin B 13 (2023) 3208–3237] 作者对“中药植物的神经保护作用——综述”的更正[药物学报B 13 (2023) 3208-3237]

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2024.12.002

João Moreira , Mariana Machado , Mónica Dias-Teixeira , Ricardo Ferraz , Cristina Delerue-Matos , Clara Grosso

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Multi region dissection of Alzheimer's brain at single cell level 单细胞水平上阿尔茨海默病脑的多区域解剖

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2024.12.010

Meng Mao , Chengming Wang , Xiwen Ma , Jianping Ye

引用次数: 0