Acta Pharmaceutica Sinica. B最新文献_第3页

Cover Story 封面故事

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-04-17 DOI: 10.1016/S2211-3835(26)00136-X

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Aberrant astroglial Kir4.1 activation in the anterior cingulate cortex disrupts neuronal excitability and social behavior 异常星形胶质Kir4.1激活在前扣带皮层破坏神经元的兴奋性和社会行为

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 10.1016/j.apsb.2026.01.029

Zhengmao Li , Yixuan Zhang , Yan Chen , Ying Zhang , Yunlong Pan , Kerui Wang , Chen Li , Xiangyu Zhao , Weikang Hu , Yifan Luo , Jiawen Cheng , Hongzhen Zhang , Kohji Fukunaga , Yankai Xia , Jiandong Jiang , Xiuxiu Liu , Feng Han , Yingmei Lu

{"title":"Aberrant astroglial Kir4.1 activation in the anterior cingulate cortex disrupts neuronal excitability and social behavior","authors":"Zhengmao Li , Yixuan Zhang , Yan Chen , Ying Zhang , Yunlong Pan , Kerui Wang , Chen Li , Xiangyu Zhao , Weikang Hu , Yifan Luo , Jiawen Cheng , Hongzhen Zhang , Kohji Fukunaga , Yankai Xia , Jiandong Jiang , Xiuxiu Liu , Feng Han , Yingmei Lu","doi":"10.1016/j.apsb.2026.01.029","DOIUrl":"10.1016/j.apsb.2026.01.029","url":null,"abstract":"<div><div>Prenatal herbicide exposure is increasingly linked to neurodevelopmental disorders, yet effective pharmacological interventions remain lacking due to unclear pathogenic mechanisms. Here, we demonstrate that prenatal exposure to glufosinate ammonium (GLA), a widely used herbicide, triggers autism-like behaviors, including social deficits and repetitive grooming, in offspring mice. Whole-brain c-Fos mapping, <em>in vivo</em> calcium imaging, and patch-clamp recordings identified hypoactive pyramidal neurons in the anterior cingulate cortex (ACC) as the neural substrate of these behavioral deficits in prenatally GLA-exposed offspring mice. Mechanistically, transcriptomic and multi-omics analyses revealed that astrocyte activation in the ACC drove Kir4.1 potassium channel upregulation, which suppressed CaMKII<em>α</em><sup>+</sup> neuronal excitability <em>via</em> impaired astrocyte–neuron communication. Pharmacological inhibition of astroglial Kir4.1 not only restored neuronal activity but also rescued social deficits in GLA-exposed offspring, underscoring Kir4.1’s pivotal role in ACC dysfunction. Our study uncovers a novel astrocyte–neuron axis underlying herbicide-induced neurodevelopmental impairments and identifies Kir4.1 as a therapeutic target for environmental factor-associated autism.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2357-2374"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706603","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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An oral immune enhancer with excellent biocompatibility for effectively strengthening body’s immunity and treating cancer 具有良好生物相容性的口服免疫增强剂，可有效增强机体免疫力，治疗癌症

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.apsb.2026.01.041

Anqi Xie , Lei Feng , Yaping Shao , Yiqun Wan , Ying Zhang , Zheyi Liu , Haihua Ji , Hao Wan

{"title":"An oral immune enhancer with excellent biocompatibility for effectively strengthening body’s immunity and treating cancer","authors":"Anqi Xie , Lei Feng , Yaping Shao , Yiqun Wan , Ying Zhang , Zheyi Liu , Haihua Ji , Hao Wan","doi":"10.1016/j.apsb.2026.01.041","DOIUrl":"10.1016/j.apsb.2026.01.041","url":null,"abstract":"<div><div>Enhancing immunity offers a versatile yet effective strategy for treating or preventing diseases. Here, we obtained a new polysaccharide (AFP-80) from <em>Anoectochilus formosanus</em> that unexpectedly stimulated immune systems without causing any detectable adverse effects. AFP-80 was applied to encapsulate <em>Lactobacillus plantarum</em> (LP), a probiotic with immunoregulatory properties, through bridging by Fe<sup>3+</sup>–tannic acid network (Fe–TA) to establish an oral immune enhancer (LP@Fe-TA@AFP-80). Upon oral administration, LP@Fe-TA@AFP-80 colonized intestines with high survival rates, aided by gastrointestinal stress-shielding and adhesive properties of AFP-80 and Fe–TA, respectively, leading to synergistic immuno-enhancing effects through combining AFP-80 and live LP. As a result, in immunocompromised mice, LP@Fe-TA@AFP-80 significantly renovated immune functions, which was deciphered to be closely associated with the rebalance of gut microbiota toward a profile with positively-immunoregulatory bacteria enriched as well as the involvement of peroxisome proliferators-activated receptor signaling pathway activation. Additionally, LP@Fe-TA@AFP-80 effectively treated cancer, <em>e.g.</em>, 4T1 breast and MC38 colon tumors, either alone or in combination with immune checkpoint blockade therapy, by remodeling tumor immune microenvironment and gut microbiota. Moreover, LP@Fe-TA@AFP-80 demonstrated excellent biocompatibility, as directly revealed by negligible biotoxicity even after 6 months of consecutive ingestion, highlighting its great potential to be implemented into people’s daily life for disease prevention.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2474-2497"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706753","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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Pathology-directed drug delivery strategies: How to overcome blood–brain barrier for the treatment of brain diseases 病理导向给药策略：如何克服血脑屏障治疗脑部疾病

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-10-22 DOI: 10.1016/j.apsb.2025.10.016

Yun Chen , Xinzhu Sun , Yilong Xi , Zhenyu Luo , Huarong Lai , Dongxin Zhu , Yifan Zhang , Fenglin Xu , Jian Li , Jianping Zhou , Yang Ding , Huaqing Zhang

{"title":"Pathology-directed drug delivery strategies: How to overcome blood–brain barrier for the treatment of brain diseases","authors":"Yun Chen , Xinzhu Sun , Yilong Xi , Zhenyu Luo , Huarong Lai , Dongxin Zhu , Yifan Zhang , Fenglin Xu , Jian Li , Jianping Zhou , Yang Ding , Huaqing Zhang","doi":"10.1016/j.apsb.2025.10.016","DOIUrl":"10.1016/j.apsb.2025.10.016","url":null,"abstract":"<div><div>Despite the different degrees of blood–brain barrier (BBB) damage in diverse brain diseases, it remains a formidable barrier that restricts most drugs from penetrating the brain. A comprehensive understanding and elucidation of the disease-specific changes of BBB in various brain pathologies are essential for directing the customized brain-targeted drug delivery systems, potentially improving cerebral delivery efficiency and therapeutic efficacy. Hence, this review compared anatomical and physiological changes of BBB under healthy and pathological states and discussed the effects of these changes on cerebral delivery efficiency. Thereafter, a particular emphasis was placed on the pathology-directed drug delivery strategies tailored to different brain diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and brain tumors. By combining insights from cutting-edge studies and emerging technologies, we proposed forward-looking suggestions on future directions to brain-targeted drug delivery, thereby improving the therapeutic efficacy and accelerating the translation from preclinical attempts into clinical practice.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2250-2281"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706761","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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Editorial of special column of hot topic reviews in drug delivery (II) 《给药热点评论》专题编辑（二）

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-04-17 DOI: 10.1016/j.apsb.2026.03.002

Wei Wu , Wei He , Zongming Zhao

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Editor Profiles: Guest Editors of Special Column on Hot Topic Reviews in Drug (II) 编辑简介：《药物热点评论专题（二）》特约编辑

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2026-04-17 DOI: 10.1016/j.apsb.2026.03.049

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Albumin-based nanocarriers: Singularities, synthesis methods, clinical relevance and targeting strategies in cancer 基于白蛋白的纳米载体：在癌症中的独特性、合成方法、临床相关性和靶向策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-12-03 DOI: 10.1016/j.apsb.2025.11.035

Edgar Pérez-Herrero , Alberto Fernández-Medarde , Juan M. Irache

{"title":"Albumin-based nanocarriers: Singularities, synthesis methods, clinical relevance and targeting strategies in cancer","authors":"Edgar Pérez-Herrero , Alberto Fernández-Medarde , Juan M. Irache","doi":"10.1016/j.apsb.2025.11.035","DOIUrl":"10.1016/j.apsb.2025.11.035","url":null,"abstract":"<div><div>Proteins have emerged as highly promising biomaterials for the design of drug-loaded nanocarriers due to their biocompatibility, biodegradability and reduced immunogenicity. Among them, albumin stands out as the most widely used due to its unique physicochemical and biological properties, high affinity to important cell surface receptors, structural stability, long circulation time and intrinsic binding capacities. This review provides an overview of the advantages and limitations of the main proteins that have been proposed as biomaterials for nanoparticle fabrication, with a specific focus on albumin-based systems. It explores the physicochemical characteristics of these nanosystems, receptor binding affinity and functionalization strategies for both passive and active tumor targeting. The main synthesis methods and functionalization strategies are discussed, highlighting their relevance in cancer therapy. Their clinical relevance is stressed by the US Food and Drug Administration (FDA)-approved formulations and the additional albumin-bound drugs in ongoing trials. Despite promising preclinical data and numerous active targeting approaches reported, clinical translation remains limited. This review provides the necessary information to develop improved strategies and cover the gap between preclinical research and clinical application and outlines future perspectives for enhancing the therapeutic efficacy and specificity of albumin-based drug delivery nanosystems in oncology.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 1883-1913"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706755","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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In situ rewiring TAMs as annihilators by “Spark-relay” nanoinitiator with flexible reactant ratio for amplifying solid tumor immunotherapy 利用具有柔性反应物比的“火花接力”纳米引发剂原位重布线TAMs作为湮灭剂用于实体瘤免疫放大治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-10-28 DOI: 10.1016/j.apsb.2025.10.036

Xinping Luo, Yingmeng Jiang, Qing Zhang, Jie Yu, Chenxi Zhou, Zhanwei Zhou, Minjie Sun

{"title":"In situ rewiring TAMs as annihilators by “Spark-relay” nanoinitiator with flexible reactant ratio for amplifying solid tumor immunotherapy","authors":"Xinping Luo, Yingmeng Jiang, Qing Zhang, Jie Yu, Chenxi Zhou, Zhanwei Zhou, Minjie Sun","doi":"10.1016/j.apsb.2025.10.036","DOIUrl":"10.1016/j.apsb.2025.10.036","url":null,"abstract":"<div><div>Tailoring tumor-associated macrophages (TAMs) into the tumoricidal phenotype represents a high-profile strategy for tumor immunotherapy. However, the existing TAMs repolarization strategies are restricted by hostile microenvironmental stress and metabolic compensation, leading to limited anti-tumor phenotype sustainability. Herein, a “Spark-Relay” nanoinitiator (SRN) with flexible S/R reactant ratio was meticulously designed for rewiring TAMs as tumoricidal bioreactor and precisely overcome metabolic compensation. Briefly, SRN reshaped TAMs <em>in situ</em> relying on tissue tropism of macrophage membrane, firstly upregulating their reactive oxygen species (ROS) production <em>via</em> burst release of Spark element and initially shifting the TAMs into the anti-tumoral phenotype, subsequently elevating NO production by releasing Relay element, which is converted to NO <em>via</em> reaction with ROS and iNOS, leading to the generation of additional ROS and creating a positive feedback loop, thereby strengthening the metabolic rewiring of TAMs from passively defensive oxidative phosphorylation to positively offensive glycolysis, which significantly enhanced the antitumoral activity of TAMs and shrunk tumor immunosuppressive microenvironment, emerging as 5.5-fold increase of tumor-suppressive/supportive ratio (TSSR) of TAMs, 4.0-fold elevation of CD8<sup>+</sup> T cell infiltration, contributing to a satisfactory tumoricidal efficacy and providing a cascade amplification mode for TAMs-based cancer therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2513-2526"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706203","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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Novel liquid-based approaches for transmucosal drug delivery 经粘膜给药的新型液体方法

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-12-30 DOI: 10.1016/j.apsb.2025.12.042

Daniélle van Staden, Hendrik J.R. Lemmer, Wilna Liebenberg, Josias H. Hamman

{"title":"Novel liquid-based approaches for transmucosal drug delivery","authors":"Daniélle van Staden, Hendrik J.R. Lemmer, Wilna Liebenberg, Josias H. Hamman","doi":"10.1016/j.apsb.2025.12.042","DOIUrl":"10.1016/j.apsb.2025.12.042","url":null,"abstract":"<div><div>Advancements in drug discovery, such as artificial intelligence, computational technology, and combinatorial chemistry, have led to numerous new promising drug candidates. However, most still fail to reach the market due to poor physicochemical properties, resulting in off-target or toxic effects. As a potential solution, non-invasive and targeted drug delivery at mucosal surfaces can deliver drugs directly to therapeutic sites to avoid off-target effects, decrease required drug doses, bypass hepatic first-pass metabolism, and circumvent uncontrolled drug release. Liquid-based drug delivery systems have advanced tremendously over recent years, with novel dosage forms such as ionic liquids, liquid crystals, stimuli-responsive phase transforming liquid systems, nanoemulsions, double-emulsions, self-emulsifying delivery systems, and eutectic systems being developed. These systems hold vast promise for transmucosal drug delivery as liquids generally provide superior spreadability compared to solid dosage forms, and some liquid systems provide prolonged mucosal retention times compared to conventional solutions. However, liquid dosage forms present regulatory challenges such as preservation, sterility, and stability requirements. This review discusses novel liquid-based formulation approaches to cross the ocular-, nasal-, oromucosal-, and vaginal mucosal barriers emphasizing advanced liquid drug delivery systems and the progress made toward clinical translation as a platform for future transmucosal liquid-based dosage form development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2119-2152"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706204","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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Isoalantolactone induces AML pyroptosis and potentiates α-PD-1 efficacy by targeting selenoprotein TXNRD1 异丙酸内酯通过靶向硒蛋白TXNRD1诱导AML焦亡并增强α-PD-1的疗效

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2026-04-01 Epub Date: 2025-12-29 DOI: 10.1016/j.apsb.2025.12.040

Xiaoxuan Yu , Yanyu Zhou , Shibo Sun , Lu Tang , Wan Zhang , Jianqiang Xu , Wukun Liu

{"title":"Isoalantolactone induces AML pyroptosis and potentiates α-PD-1 efficacy by targeting selenoprotein TXNRD1","authors":"Xiaoxuan Yu , Yanyu Zhou , Shibo Sun , Lu Tang , Wan Zhang , Jianqiang Xu , Wukun Liu","doi":"10.1016/j.apsb.2025.12.040","DOIUrl":"10.1016/j.apsb.2025.12.040","url":null,"abstract":"<div><div>The suppressive microenvironment of AML limits anti-PD-1 efficacy, making pyroptosis induction a key strategy for its remodeling. Isoalantolactone (IAL), a naturally occurring small molecule, has been identified herein to inhibit cytosolic thioredoxin reductase1 (TXNRD1) and trigger pyroptosis in AML cells, thereby enhancing the efficacy of anti-PD-1 antibody therapy. Mechanistically, the <em>α</em>,<em>β</em>-unsaturated carbonyl group of IAL covalently bound to the selenocysteine residue at the position 498 (Sec<sup>498</sup>) of TXNRD1 through a Michael addition reaction. Clinical sample analysis revealed that TXNRD1 is overexpressed in AML, which correlates with poor prognosis. Additionally, we found that the TXNRD inhibitor auranofin has demonstrated good efficacy against AML. The inhibition of TXNRD1 activates the transcription factor peroxisome proliferator-activated receptor gamma (PPAR<em>γ</em>), which, in turn, upregulates the transcription of caspase-3, subsequently increasing the cleavage of gasdermin E to induce pyroptosis <em>via</em> the non-classical pathway in AML cells. Additionally, enhanced caspase-3 activity promotes poly ADP-ribose polymerase 1 (PARP-1) cleavage and upregulates PD-L1 expression, thereby increasing sensitivity to anti-PD-1 monoclonal antibodies. Overall, the current study highlights a promising approach for augmenting therapy using anti-PD-1 monoclonal antibodies in AML by targeting TXNRD1 to induce pyroptosis and ameliorate the immunosuppressive microenvironment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 4","pages":"Pages 2317-2331"},"PeriodicalIF":14.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706206","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