Acta Pharmaceutica Sinica. B最新文献

英文中文

AT-17 redefines local anesthetics by targeting mitochondrial apoptosis AT-17通过靶向线粒体凋亡重新定义局麻药

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.10.013

Xiaoyuan Chen

引用次数: 0

Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management 新一代临床相关抗体检测：解锁电化学生物传感器用于重大疾病管理

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.08.016

Zheng Zhao , Zhiwei Chen , Jacques Crommen , Shengfeng Huang , Qiqin Wang , Zhengjin Jiang

Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

自身免疫性疾病、癌症和病毒感染分别以慢性病理、不受调节的细胞增殖和快速传播为特征，对全球健康构成重大威胁，需要紧急预警和治疗策略。抗体根据其临床作用，主要分为自身抗体和治疗性抗体，为这些严重疾病的精确诊断和治疗提供了重要信息，并显示出相当大的价值。在生物分析应用的技术中，电化学生物传感器以其快速响应、高灵敏度、小型化、低成本、易操作等独特优势，已成为药物精确诊断和治疗监测的发展趋势。本文系统地综述了临床相关抗体在自身免疫性疾病、癌症和病毒感染中的关系和作用，并详细介绍了相关电化学生物传感器的组成、策略、发展和应用趋势。此外，它强调了电化学传感器在临床相关抗体背景下的进步和前景的挑战和机遇。

{"title":"Next-generation clinically relevant antibody detection: Unlocking electrochemical biosensors for critical disease management","authors":"Zheng Zhao , Zhiwei Chen , Jacques Crommen , Shengfeng Huang , Qiqin Wang , Zhengjin Jiang","doi":"10.1016/j.apsb.2025.08.016","DOIUrl":"10.1016/j.apsb.2025.08.016","url":null,"abstract":"<div><div>Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5632-5662"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475562","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

Engineered plant extracellular vesicles: Emerging nanoplatforms for combinational cancer immunotherapy 工程植物细胞外囊泡：联合癌症免疫治疗的新兴纳米平台

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.08.020

Fucai Chen , Rongrong Bao , Wanyi Yang , Yijing Lu , Jiaxin Guo , Wenjing Chen , Jiale Li , Kuanhan Feng , Wen Zhang , Liuqing Di , Liang Feng , Ruoning Wang

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

植物源性细胞外囊泡（PDEVs）是指植物释放的一组纳米颗粒。这些颗粒的特点是脂质双层结构，含有各种蛋白质、脂质、核酸和独特的代谢物。虽然PDEVs的研究相对较新，只有十年左右的时间，但在基础研究和临床转化领域都显示出良好的发展前景。证据表明，PDEVs在调节炎症和治疗肿瘤方面具有良好的应用前景。它们独特的囊泡模拟结构和恒星生物相容性使它们成为运送各种抗癌药物（包括RNA、蛋白质和传统化疗药物）的首选候选者。越来越多的研究表明，PDEVs可以被设计为联合癌症免疫治疗的创新平台。因此，本文对PDEVs在癌症治疗和联合癌症免疫治疗中的工程方法和策略的最新进展进行了广泛的总结。本文综述了PDEVs的基本特征，包括其生物发生过程和组成，抗肿瘤活性和机制。最后，讨论了pdev作为递送载体的体内安全性以及规模化生产和临床转化的挑战。

{"title":"Engineered plant extracellular vesicles: Emerging nanoplatforms for combinational cancer immunotherapy","authors":"Fucai Chen , Rongrong Bao , Wanyi Yang , Yijing Lu , Jiaxin Guo , Wenjing Chen , Jiale Li , Kuanhan Feng , Wen Zhang , Liuqing Di , Liang Feng , Ruoning Wang","doi":"10.1016/j.apsb.2025.08.020","DOIUrl":"10.1016/j.apsb.2025.08.020","url":null,"abstract":"<div><div>Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the <em>in vivo</em> safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5663-5701"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475563","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

Sorafenib promotes the E3 ubiquitin ligase FBXW7 to increase tau degradation and ameliorate tauopathies 索拉非尼促进E3泛素连接酶FBXW7增加tau降解和改善tau病变

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.09.024

Yunqiang Zhou , Yong Wang , Huiying Yang , Chi Zhang , Jian Meng , Lingliang Zhang , Kun Li , Ling-ling Huang , Xian Zhang , Hong Luo , Yunwu Zhang

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin–proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

tau病，包括阿尔茨海默病（AD），是一系列以微管相关蛋白tau的病理积累为特征的神经退行性疾病。由于神经细胞中tau蛋白的异常修饰和沉积对tau病的病因至关重要，因此降低tau蛋白水平的方法，如促进tau蛋白降解，可能成为疾病治疗的有效策略。通过筛选fda批准的药物，我们发现索拉非尼显著降低了总tau蛋白和磷酸化tau蛋白水平。我们发现索拉非尼治疗减轻了PS19 tau模型小鼠的认知缺陷和tau病理。在机制上，我们发现索拉非尼抑制参与tau磷酸化的多种激酶并促进自噬。重要的是，我们进一步证明了索拉非尼还促进了E3泛素连接酶FBXW7的表达，该酶可以通过泛素-蛋白酶体途径结合tau并介导tau降解。最后，我们发现FBXW7在AD患者和tau模型小鼠的大脑中表达下降，并且FBXW7在海马中的过度表达减轻了PS19小鼠的认知缺陷和tau病理。这些结果表明索拉非尼可能通过促进tau降解和降低tau磷酸化而成为一种有希望的治疗tau病的选择，并且靶向FBXW7也可以作为tau病的替代治疗策略。

{"title":"Sorafenib promotes the E3 ubiquitin ligase FBXW7 to increase tau degradation and ameliorate tauopathies","authors":"Yunqiang Zhou , Yong Wang , Huiying Yang , Chi Zhang , Jian Meng , Lingliang Zhang , Kun Li , Ling-ling Huang , Xian Zhang , Hong Luo , Yunwu Zhang","doi":"10.1016/j.apsb.2025.09.024","DOIUrl":"10.1016/j.apsb.2025.09.024","url":null,"abstract":"<div><div>Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin–proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5817-5831"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475567","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

A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis 一种有前途的新型局部麻醉剂，通过减少线粒体相关的细胞凋亡来有效麻醉口腔炎症

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.09.001

Haofan Wang , Yihang Hao , Wenrui Gai , Shilong Hu , Wencheng Liu , Bo Ma , Rongjia Shi , Yongzhen Tan , Ting Kang , Ao Hai , Yi Zhao , Yaling Tang , Ling Ye , Jin Liu , Xinhua Liang , Bowen Ke

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17’s inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

局部麻醉剂（LAs），如阿替卡因（AT），在炎症环境中表现出有限的疗效，这对其在口腔医学中的临床应用构成了重大限制。在我们之前的研究中，我们开发了AT-17，它在慢性炎症条件下表现出有效的特性，似乎是一种新的口服LA，可以解决这一挑战。在本研究中，我们进一步阐明了AT-17在急性炎症中的有益作用，特别是在口腔急性炎症中，线粒体相关的凋亡起着至关重要的作用。结果表明，AT-17通过改善线粒体功能障碍，有效抑制脂多糖（LPS）诱导的神经细胞凋亡。这一过程包括抑制线粒体活性氧（mtROS）的产生和随后NRF2通路的激活。最值得注意的是，线粒体相关凋亡的改善是AT-17抑制电压门控钠通道的关键因素。此外，AT-17被证明通过Na+/NCLX/ETC信号轴减少神经细胞中mtROS的产生。总之，我们已经开发了一种新的局部麻醉剂，通过增强线粒体相关的细胞凋亡，在炎症条件下表现出明显的麻醉功能。这一进展对未来的药物开发和加深我们对潜在作用机制的理解具有相当大的希望。

{"title":"A promising novel local anesthetic for effective anesthesia in oral inflammatory conditions through reducing mitochondria-related apoptosis","authors":"Haofan Wang , Yihang Hao , Wenrui Gai , Shilong Hu , Wencheng Liu , Bo Ma , Rongjia Shi , Yongzhen Tan , Ting Kang , Ao Hai , Yi Zhao , Yaling Tang , Ling Ye , Jin Liu , Xinhua Liang , Bowen Ke","doi":"10.1016/j.apsb.2025.09.001","DOIUrl":"10.1016/j.apsb.2025.09.001","url":null,"abstract":"<div><div>Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction <em>in vitro</em>. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17’s inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na<sup>+</sup>/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5854-5866"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475577","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

Arsenic trioxide-based nanoparticles for enhanced chemotherapy by activating pyroptosis 基于三氧化二砷的纳米颗粒通过激活焦亡来增强化疗

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.08.003

Shengmei Wang , Ding Ma , Minghua Yang , Ye Zhang , Shengfeng Wang , Wenhu Zhou

Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3-GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano self-assemblies formed through ion pairing between Mn²⁺ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn²⁺, and Dz. Mn²⁺ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO's direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

化疗仍然是肝细胞癌（HCC）的主要治疗选择，但其临床疗效往往不令人满意。本研究以三氧化二砷（ATO）为模型，阐明了自噬抑制在调节细胞对化疗反应中的作用，通过caspase-3-GSDME途径将细胞死亡从凋亡转变为焦亡，从而增强抗肿瘤疗效。在这些发现的基础上，研究人员开发了一种能够抑制自噬促进焦亡的ATO纳米药物递送系统，以增强肿瘤治疗。叶酸修饰的白蛋白作为稳定剂，通过Mn2+和ATO之间的离子配对形成纳米自组装，包封靶向Beclin 1的DNAzyme (Dz)， Beclin 1是一个关键的自噬调节因子。表征研究证实了ATO和Dz在纳米颗粒内的有效封装，旨在在细胞内微环境中分解，释放全活性成分，即ATO， Mn2+和Dz。Mn2+作为金属辅助因子激活Dz进行Beclin 1 mRNA的切割，抑制自噬，增强ato诱导的细胞焦亡。升高的细胞焦亡水平不仅增强了ATO对肿瘤细胞的直接杀伤能力，还能引发抗肿瘤免疫反应，协同增强疗效。经静脉注射后，纳米药物在肿瘤组织中积累并靶向肝癌细胞。与游离ATO相比，纳米药物在体内的抗肿瘤作用显著提高，在小鼠体内达到100%的45天存活率，具有良好的生物安全性。这项研究为肿瘤化疗致敏提供了新的见解，并为ATO纳米制剂的开发提供了一个有前途的策略。

{"title":"Arsenic trioxide-based nanoparticles for enhanced chemotherapy by activating pyroptosis","authors":"Shengmei Wang , Ding Ma , Minghua Yang , Ye Zhang , Shengfeng Wang , Wenhu Zhou","doi":"10.1016/j.apsb.2025.08.003","DOIUrl":"10.1016/j.apsb.2025.08.003","url":null,"abstract":"<div><div>Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis <em>via</em> the caspase-3-GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano self-assemblies formed through ion pairing between Mn<sup>2+</sup> and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, <em>i.e.</em>, ATO, Mn<sup>2+</sup>, and Dz. Mn<sup>2+</sup> acted as a metal cofactor to activate Dz for <em>Beclin</em> 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO's direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved <em>in vivo</em> anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 6001-6018"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476100","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

Amino acid restriction in obesity management: Inducing energy discharge 控制肥胖中的氨基酸限制：诱导能量释放

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.07.013

Lili Yu , Jianping Ye

引用次数: 0

Application of artificial intelligence in laboratory hematology: Advances, challenges, and prospects 人工智能在实验室血液学中的应用：进展、挑战与展望

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.05.036

Hongyan Liao , Feng Zhang , Fengyu Chen , Yifei Li , Yanrui Sun , Darcée D. Sloboda , Qin Zheng , Binwu Ying , Tony Hu

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

血液学疾病的诊断目前是根据不同测试的综合结果建立的，包括那些评估形态学(M)、免疫表型(I)、细胞遗传学(C)和分子生物学(M)的测试（统称为MICM分类）。在这个工作流中，大多数结果都是手动解释的（即，由一个人，没有自动化），这是依赖于专业知识的，劳动密集型的，耗时的，并且具有内在的观察者之间的可变性。此外，随着仪器和技术的进步，数据的维度和吞吐量越来越高，这给人工分析带来了额外的挑战。最近，人工智能（AI）已经成为临床血液学的一个有前途的工具，以确保及时诊断，精确的风险分层和治疗成功。在这篇综述中，我们总结了当前人工智能模型的进展、局限性和挑战，并提出了在MICM管道的每个部门中提高其性能的潜在策略。最后，我们分享观点，强调未来的发展方向，并呼吁广泛的跨学科合作，以人类水平的智慧策略完善人工智能，促进其融入临床工作流程。

{"title":"Application of artificial intelligence in laboratory hematology: Advances, challenges, and prospects","authors":"Hongyan Liao , Feng Zhang , Fengyu Chen , Yifei Li , Yanrui Sun , Darcée D. Sloboda , Qin Zheng , Binwu Ying , Tony Hu","doi":"10.1016/j.apsb.2025.05.036","DOIUrl":"10.1016/j.apsb.2025.05.036","url":null,"abstract":"<div><div>The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (<em>i.e.</em>, by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5702-5733"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475564","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

Technologies and applications of current human cardiac organoids 当前人类心脏类器官的技术与应用

IF 14.6 1区医学 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/j.apsb.2025.09.013

Huan-Yu Zhao , Jie-Bing Jiang , Shu-Na Wang, Chao-Yu Miao

Human self-organizing cardioids, a recent breakthrough in cardiac organoid research, are constructed with the specialized cardiac lineage cells derived from human pluripotent stem cells (hPSCs) and have made rapid advancements since 2021. A key advantage of these organoids is their minimal reliance on external interventions, allowing them to more accurately replicate the heart's developmental processes through intrinsic signaling pathways, thereby closely mimicking natural cardiac characteristics. Consequently, they hold significant promise for improving drug safety evaluations, treating both congenital and acquired heart diseases, advancing eugenics practices, developing humanized cardiac disease models, conducting research in regenerative medicine, and understanding how unique environments (such as aerospace) affect human health. This review systematically describes the current various self-organizing cardioid construction techniques, comparing the structural differences caused by diverse signal stimulations, which would be instrumental in optimizing designs for more advanced and mature cardioids. Additionally, we summarize existing applications and address the challenges faced. Despite some uncertainties and challenges in current technologies and applications, this emerging cardiac organoid technology holds promise to provide new possibilities for cardiovascular medicine through continuous refinement.

人类自组织类心脏细胞是人类多能干细胞（hPSCs）衍生的特化心脏谱系细胞构建的心脏类器官研究的最新突破，自2021年以来取得了快速进展。这些类器官的一个关键优势是它们对外部干预的依赖最小，使它们能够通过内在信号通路更准确地复制心脏的发育过程，从而密切模仿自然心脏特征。因此，它们在改善药物安全性评估、治疗先天性和获得性心脏病、推进优生学实践、开发人性化心脏病模型、开展再生医学研究以及了解独特环境（如航空航天）如何影响人类健康方面具有重大前景。本文系统介绍了目前各种自组织类心结构构建技术，比较了不同信号刺激引起的结构差异，为更先进、更成熟的类心结构优化设计提供参考。此外，我们总结了现有的应用并解决了面临的挑战。尽管目前的技术和应用存在一些不确定性和挑战，但这种新兴的心脏类器官技术有望通过不断完善为心血管医学提供新的可能性。

{"title":"Technologies and applications of current human cardiac organoids","authors":"Huan-Yu Zhao , Jie-Bing Jiang , Shu-Na Wang, Chao-Yu Miao","doi":"10.1016/j.apsb.2025.09.013","DOIUrl":"10.1016/j.apsb.2025.09.013","url":null,"abstract":"<div><div>Human self-organizing cardioids, a recent breakthrough in cardiac organoid research, are constructed with the specialized cardiac lineage cells derived from human pluripotent stem cells (hPSCs) and have made rapid advancements since 2021. A key advantage of these organoids is their minimal reliance on external interventions, allowing them to more accurately replicate the heart's developmental processes through intrinsic signaling pathways, thereby closely mimicking natural cardiac characteristics. Consequently, they hold significant promise for improving drug safety evaluations, treating both congenital and acquired heart diseases, advancing eugenics practices, developing humanized cardiac disease models, conducting research in regenerative medicine, and understanding how unique environments (such as aerospace) affect human health. This review systematically describes the current various self-organizing cardioid construction techniques, comparing the structural differences caused by diverse signal stimulations, which would be instrumental in optimizing designs for more advanced and mature cardioids. Additionally, we summarize existing applications and address the challenges faced. Despite some uncertainties and challenges in current technologies and applications, this emerging cardiac organoid technology holds promise to provide new possibilities for cardiovascular medicine through continuous refinement.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 11","pages":"Pages 5734-5757"},"PeriodicalIF":14.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145475565","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 Q1 PHARMACOLOGY & PHARMACY

Acta Pharmaceutica Sinica. B

Pub Date : 2025-11-01 DOI: 10.1016/S2211-3835(25)00662-8

引用次数: 0

首页上一页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Acta Pharmaceutica Sinica. B

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀