Pub Date : 2026-01-01Epub Date: 2025-09-24DOI: 10.1016/j.apsb.2025.09.037
Yaqi Yuan , Peng Jiang , Chuan Xiao , Jiapeng Lei , Bo Cheng , Hankun Hu , Wei Li
Psoriasis is a prevalent chronic inflammatory skin disorder, characterized by epidermal thickening and an inflammatory hypoxic microenvironment, which significantly hinder drug penetration through the thickened skin and limit the efficacy of photodynamic therapy (PDT). Here, we introduce a dual-section microneedle (MN) patch (termed S-PTP MN patch) to enhance the therapeutic efficacy of psoriasis treatment. The needle section contains PTP nanoparticles (NPs) loaded with triamcinolone acetonide (TA) and coated with a reactive oxygen species (ROS)-responsive layer, while the base section of the patch encapsulates sodium percarbonate (SPC) particles that serve as oxygen generators to facilitate deep penetration of the PTP NPs into inflammatory sites and improve PDT efficacy. Moreover, the PTP NPs enable sustained release of TA drug over 6 days, demonstrating potent anti-inflammatory activity. In an imiquimod-induced psoriatic mouse model, a single application of the S-PTP MN patch demonstrated superior therapeutic efficacy compared to the conventional topical TA cream, with significantly alleviated clinical symptoms, reduced epidermal thickness, and lowered inflammatory cytokine levels, highlighting the potential of the S-PTP MN patch as a clinically translatable strategy for effective psoriasis therapy.
{"title":"Oxygen-boosted dual-section microneedle patch for enhanced drug penetration and improved photodynamic and anti-inflammatory therapy in psoriasis","authors":"Yaqi Yuan , Peng Jiang , Chuan Xiao , Jiapeng Lei , Bo Cheng , Hankun Hu , Wei Li","doi":"10.1016/j.apsb.2025.09.037","DOIUrl":"10.1016/j.apsb.2025.09.037","url":null,"abstract":"<div><div>Psoriasis is a prevalent chronic inflammatory skin disorder, characterized by epidermal thickening and an inflammatory hypoxic microenvironment, which significantly hinder drug penetration through the thickened skin and limit the efficacy of photodynamic therapy (PDT). Here, we introduce a dual-section microneedle (MN) patch (termed S-PTP MN patch) to enhance the therapeutic efficacy of psoriasis treatment. The needle section contains PTP nanoparticles (NPs) loaded with triamcinolone acetonide (TA) and coated with a reactive oxygen species (ROS)-responsive layer, while the base section of the patch encapsulates sodium percarbonate (SPC) particles that serve as oxygen generators to facilitate deep penetration of the PTP NPs into inflammatory sites and improve PDT efficacy. Moreover, the PTP NPs enable sustained release of TA drug over 6 days, demonstrating potent anti-inflammatory activity. In an imiquimod-induced psoriatic mouse model, a single application of the S-PTP MN patch demonstrated superior therapeutic efficacy compared to the conventional topical TA cream, with significantly alleviated clinical symptoms, reduced epidermal thickness, and lowered inflammatory cytokine levels, highlighting the potential of the S-PTP MN patch as a clinically translatable strategy for effective psoriasis therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 458-469"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941493","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}
Pub Date : 2026-01-01Epub Date: 2025-09-18DOI: 10.1016/j.apsb.2025.09.026
Hengyue Shan , Yuzheng Zhou , Ying Qin , Taijie Guo , Xiao Zhang , Huaijiang Xiang , Qinyang He , Chen Shi , Dekang Li , Jingli Liu , Chunting Qi , Shi Chen , Jiajia Dong , Gang Xu , Ying Li , Zheng Zhang , Li Tan
SARS-CoV-2 continues to propagate globally, posing non-negligible risks of severe COVID-19. Although several clinical antivirals and immunosuppressants offer crucial protection, there is a persistent need for additional therapeutic options to counter emerging viral variants and drug resistances. New strategies focusing on host targets, or simultaneously suppressing viral replication and inflammation, particularly require rigorous validation. Compared to established antiviral targets, PLpro presents an alternative actionable vulnerability in SARS-CoV-2 infection. Meanwhile, RIPK1 was pinpointed to enhance both viral replication and the resulting cytokine storm in host cells. However, inhibitors targeting PLpro or RIPK1 require further optimization for preclinical studies, and their combined efficacy in vivo has yet to be explored. Here, we report the discoveries of potent and selective PLpro inhibitors and RIPK1 inhibitors through high-throughput approaches. Our lead compounds, SHY1643 and QY1892, demonstrated synergistic and robust effects in reducing the viral loads and cytokine release syndromes in SARS-CoV-2-infected mice. These findings establish a proof-of-concept combination therapy strategy for treating severe COVID-19, and provide promising leads for the clinical drug development.
{"title":"Discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model","authors":"Hengyue Shan , Yuzheng Zhou , Ying Qin , Taijie Guo , Xiao Zhang , Huaijiang Xiang , Qinyang He , Chen Shi , Dekang Li , Jingli Liu , Chunting Qi , Shi Chen , Jiajia Dong , Gang Xu , Ying Li , Zheng Zhang , Li Tan","doi":"10.1016/j.apsb.2025.09.026","DOIUrl":"10.1016/j.apsb.2025.09.026","url":null,"abstract":"<div><div>SARS-CoV-2 continues to propagate globally, posing non-negligible risks of severe COVID-19. Although several clinical antivirals and immunosuppressants offer crucial protection, there is a persistent need for additional therapeutic options to counter emerging viral variants and drug resistances. New strategies focusing on host targets, or simultaneously suppressing viral replication and inflammation, particularly require rigorous validation. Compared to established antiviral targets, PLpro presents an alternative actionable vulnerability in SARS-CoV-2 infection. Meanwhile, RIPK1 was pinpointed to enhance both viral replication and the resulting cytokine storm in host cells. However, inhibitors targeting PLpro or RIPK1 require further optimization for preclinical studies, and their combined efficacy <em>in vivo</em> has yet to be explored. Here, we report the discoveries of potent and selective PLpro inhibitors and RIPK1 inhibitors through high-throughput approaches. Our lead compounds, SHY1643 and QY1892, demonstrated synergistic and robust effects in reducing the viral loads and cytokine release syndromes in SARS-CoV-2-infected mice. These findings establish a proof-of-concept combination therapy strategy for treating severe COVID-19, and provide promising leads for the clinical drug development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 387-405"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941528","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}
Pub Date : 2026-01-01Epub Date: 2025-11-01DOI: 10.1016/j.apsb.2025.10.043
Chunsen Yuan , Taotao Jin , Hangke Lei , Juanjuan Liu , Wendan Pu , Yang Zhang , Chenwen Li , Dingde Huang , Jianxiang Zhang , Jiawei Guo
{"title":"Author correction to “Self-illuminating liposome-derived in situ triggerable photodynamic therapy combining radionuclide therapy for synergistic treatment of lung cancer” [Acta Pharm Sin B 15 (2025) 4973–4994]","authors":"Chunsen Yuan , Taotao Jin , Hangke Lei , Juanjuan Liu , Wendan Pu , Yang Zhang , Chenwen Li , Dingde Huang , Jianxiang Zhang , Jiawei Guo","doi":"10.1016/j.apsb.2025.10.043","DOIUrl":"10.1016/j.apsb.2025.10.043","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 660-663"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941471","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}
Pub Date : 2026-01-01Epub Date: 2025-11-04DOI: 10.1016/j.apsb.2025.10.047
Baohu Li , Hui Xu , Xiaoyu Shi , Chunhua Ma , Jinfei Yang , Peng Zhan
{"title":"Clinical insight-driven novel drug development: Multidisciplinary integration and transformative opportunities","authors":"Baohu Li , Hui Xu , Xiaoyu Shi , Chunhua Ma , Jinfei Yang , Peng Zhan","doi":"10.1016/j.apsb.2025.10.047","DOIUrl":"10.1016/j.apsb.2025.10.047","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 651-655"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941472","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}
Pub Date : 2026-01-01Epub Date: 2025-10-29DOI: 10.1016/j.apsb.2025.10.032
Anqi Lin , Zhirou Zhang , Aimin Jiang , Kexin Li , Ying Shi , Hong Yang , Jian Zhang , Rongrong Liu , Yaxuan Wang , Antonino Glaviano , Quan Cheng , Bufu Tang , Zhengang Qiu , Peng Luo
With the rapid advancements in computer technology and bioinformatics, the prediction of protein–ligand-binding sites has become a central component of modern drug discovery and development. Traditional experimental methods are often constrained by long experimental cycles and high costs; therefore, the development of accurate and efficient computational methods is of paramount significance for conserving time and cost. This review comprehensively summarizes the methodological advancements and current applications in the field of screening for druggable protein target sites, systematically comparing the fundamental principles, advantages, and disadvantages of four main categories of methods: structure- and sequence-based methods, machine learning-based methods, binding site feature analysis methods, and druggability assessment methods. Subsequently, by integrating classic case studies, this paper elaborately discusses the technical support and theoretical guidance afforded by the screening of protein druggable target sites for drug discovery and drug repositioning. Finally, this paper thoroughly explores the current challenges inherent in the field of protein–ligand binding site prediction, with a particular focus on future technological trends, systematically elucidating the developmental prospects and potential applications of these predictive methods.
{"title":"Computational approaches to druggable site identification: Current status and future perspective","authors":"Anqi Lin , Zhirou Zhang , Aimin Jiang , Kexin Li , Ying Shi , Hong Yang , Jian Zhang , Rongrong Liu , Yaxuan Wang , Antonino Glaviano , Quan Cheng , Bufu Tang , Zhengang Qiu , Peng Luo","doi":"10.1016/j.apsb.2025.10.032","DOIUrl":"10.1016/j.apsb.2025.10.032","url":null,"abstract":"<div><div>With the rapid advancements in computer technology and bioinformatics, the prediction of protein–ligand-binding sites has become a central component of modern drug discovery and development. Traditional experimental methods are often constrained by long experimental cycles and high costs; therefore, the development of accurate and efficient computational methods is of paramount significance for conserving time and cost. This review comprehensively summarizes the methodological advancements and current applications in the field of screening for druggable protein target sites, systematically comparing the fundamental principles, advantages, and disadvantages of four main categories of methods: structure- and sequence-based methods, machine learning-based methods, binding site feature analysis methods, and druggability assessment methods. Subsequently, by integrating classic case studies, this paper elaborately discusses the technical support and theoretical guidance afforded by the screening of protein druggable target sites for drug discovery and drug repositioning. Finally, this paper thoroughly explores the current challenges inherent in the field of protein–ligand binding site prediction, with a particular focus on future technological trends, systematically elucidating the developmental prospects and potential applications of these predictive methods.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 62-92"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941476","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}
Pub Date : 2026-01-01Epub Date: 2025-11-13DOI: 10.1016/j.apsb.2025.11.007
Zhenzhen Zhou, Yanying Sun, Da Feng, Zhao Wang, Fabao Zhao, Shenghua Gao, Peng Zhan, Dongwei Kang, Xinyong Liu
HIV-1 reverse transcriptase (RT) is responsible for reverse transcription of viral single-stranded RNA to double-stranded DNA, which plays an important role in the replication cycle of HIV-1 and has been identified as a key target for anti-HIV-1 drug discovery. Among HIV-1 RT inhibitors, allosteric inhibitors acting on non-catalytic sites have the advantages of high efficiency and low cytotoxicity, which are the focus of the research on anti-HIV-1 inhibitors. Great progress has been achieved in the structural biology of HIV-1 RT, which significantly facilitated the development of RT allosteric inhibitors. Herein, we provided a detailed review of the co-crystal structures of small molecule allosteric inhibitors in complex with RT reported in the last decade. Moreover, the strategies to discover novel and efficient inhibitors based on co-crystal structures have also been discussed, expecting to provide a reference for the development of the next-generation anti-HIV-1 drugs.
{"title":"Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design","authors":"Zhenzhen Zhou, Yanying Sun, Da Feng, Zhao Wang, Fabao Zhao, Shenghua Gao, Peng Zhan, Dongwei Kang, Xinyong Liu","doi":"10.1016/j.apsb.2025.11.007","DOIUrl":"10.1016/j.apsb.2025.11.007","url":null,"abstract":"<div><div>HIV-1 reverse transcriptase (RT) is responsible for reverse transcription of viral single-stranded RNA to double-stranded DNA, which plays an important role in the replication cycle of HIV-1 and has been identified as a key target for anti-HIV-1 drug discovery. Among HIV-1 RT inhibitors, allosteric inhibitors acting on non-catalytic sites have the advantages of high efficiency and low cytotoxicity, which are the focus of the research on anti-HIV-1 inhibitors. Great progress has been achieved in the structural biology of HIV-1 RT, which significantly facilitated the development of RT allosteric inhibitors. Herein, we provided a detailed review of the co-crystal structures of small molecule allosteric inhibitors in complex with RT reported in the last decade. Moreover, the strategies to discover novel and efficient inhibitors based on co-crystal structures have also been discussed, expecting to provide a reference for the development of the next-generation anti-HIV-1 drugs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 93-121"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941477","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}
Pub Date : 2026-01-01Epub Date: 2025-10-24DOI: 10.1016/j.apsb.2025.10.019
Zheng Sun , Jun Ge , Hui Fu , Ziqiu Chen , Chengcheng Zhao , Xiuyan Li , Yujiao Sun , Zhonggao Gao , Yunfei Li , Yingpeng Li
Conventional drug-delivery systems (DDSs) for oncology often face challenges such as insufficient tumor selectivity, rapid systemic clearance, limited penetration across stromal and immune barriers, and suboptimal biocompatibility. Live immune cell-based drug-delivery systems (LCDDSs) overcome these limitations by exploiting the innate tumor-homing capacity, high biocompatibility, and dynamic tumor microenvironment (TME) interactions intrinsic to leukocytes, facilitating precise targeting with minimal systemic toxicity. Furthermore, immune cells act as “mobile microprocessors”, actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME. Nonetheless, the clinical translation of LCDDSs remains impeded by limited drug-loading capacities, premature payload degradation, potential impairment of immune-cell function, and insufficient persistence in immunosuppressive environments. To overcome these hurdles, immune cell reprogramming via genetic, metabolic, or epigenetic modifications emerges as a promising strategy. Such interventions improve cellular fitness, enhance tumor infiltration, augment payload transport efficiency, confer programmable release profiles, mitigate cellular exhaustion, and increase adaptability to the hostile TME. This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits, drug compatibility considerations, payload loading strategies, and design criteria essential for achieving clinical controllability, safety, and scalability. By integrating immune-cell engineering with cutting-edge drug delivery technologies, reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.
{"title":"Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives","authors":"Zheng Sun , Jun Ge , Hui Fu , Ziqiu Chen , Chengcheng Zhao , Xiuyan Li , Yujiao Sun , Zhonggao Gao , Yunfei Li , Yingpeng Li","doi":"10.1016/j.apsb.2025.10.019","DOIUrl":"10.1016/j.apsb.2025.10.019","url":null,"abstract":"<div><div>Conventional drug-delivery systems (DDSs) for oncology often face challenges such as insufficient tumor selectivity, rapid systemic clearance, limited penetration across stromal and immune barriers, and suboptimal biocompatibility. Live immune cell-based drug-delivery systems (LCDDSs) overcome these limitations by exploiting the innate tumor-homing capacity, high biocompatibility, and dynamic tumor microenvironment (TME) interactions intrinsic to leukocytes, facilitating precise targeting with minimal systemic toxicity. Furthermore, immune cells act as “mobile microprocessors”, actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME. Nonetheless, the clinical translation of LCDDSs remains impeded by limited drug-loading capacities, premature payload degradation, potential impairment of immune-cell function, and insufficient persistence in immunosuppressive environments. To overcome these hurdles, immune cell reprogramming <em>via</em> genetic, metabolic, or epigenetic modifications emerges as a promising strategy. Such interventions improve cellular fitness, enhance tumor infiltration, augment payload transport efficiency, confer programmable release profiles, mitigate cellular exhaustion, and increase adaptability to the hostile TME. This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits, drug compatibility considerations, payload loading strategies, and design criteria essential for achieving clinical controllability, safety, and scalability. By integrating immune-cell engineering with cutting-edge drug delivery technologies, reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 169-197"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941480","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}
Pub Date : 2026-01-01Epub Date: 2025-11-01DOI: 10.1016/j.apsb.2025.10.041
Yuhong Gao , Sijia Hua , Xiulin Dong , Kun Zhang , Xiaofeng Zhang , Jianfeng Yang
Vaccines play a crucial role in the prevention and treatment of multiple diseases. Given the constraints of conventional vaccines, the development of nanovaccines, characterized by their superior design flexibility and controllability, has emerged as a compelling alternative. By utilizing nanotechnology, nanovaccines optimize the targeted delivery of antigens and adjuvants, augment antigen presentation, and facilitate precise modulation of immune cell responses, thereby exhibiting substantial potential for both preventive and therapeutic applications across a range of diseases. However, research on nanovaccines is currently stalled at the preclinical stage, with numerous challenges and shortcomings hindering their clinical translation. Herein, we discuss various design concepts and strategies for nanovaccines, along with their biomedical applications, with an emphasis on the challenges, future directions, and strategies of their clinical translation. We specifically highlight the core principles that need to be achieved in the preclinical development of nanovaccines, aiming to explore strategies to overcome existing challenges and promote their clinical application.
{"title":"Concerns and challenges in clinics-guided nanovaccines design and applications","authors":"Yuhong Gao , Sijia Hua , Xiulin Dong , Kun Zhang , Xiaofeng Zhang , Jianfeng Yang","doi":"10.1016/j.apsb.2025.10.041","DOIUrl":"10.1016/j.apsb.2025.10.041","url":null,"abstract":"<div><div>Vaccines play a crucial role in the prevention and treatment of multiple diseases. Given the constraints of conventional vaccines, the development of nanovaccines, characterized by their superior design flexibility and controllability, has emerged as a compelling alternative. By utilizing nanotechnology, nanovaccines optimize the targeted delivery of antigens and adjuvants, augment antigen presentation, and facilitate precise modulation of immune cell responses, thereby exhibiting substantial potential for both preventive and therapeutic applications across a range of diseases. However, research on nanovaccines is currently stalled at the preclinical stage, with numerous challenges and shortcomings hindering their clinical translation. Herein, we discuss various design concepts and strategies for nanovaccines, along with their biomedical applications, with an emphasis on the challenges, future directions, and strategies of their clinical translation. We specifically highlight the core principles that need to be achieved in the preclinical development of nanovaccines, aiming to explore strategies to overcome existing challenges and promote their clinical application.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 198-230"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941481","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}
Pub Date : 2026-01-01Epub Date: 2025-11-13DOI: 10.1016/j.apsb.2025.11.016
Wenting Wang , Yanfei Liu , Yiwen Li , Qian Xu , Mengmeng Zhu , Jing Cui , Yue Liu
Vascular calcification (VC) is a marker of substantial vascular damage in patients with diabetes and has been recognized as a predictor of cardiovascular events and all-cause mortality. To date, no effective therapeutic strategy has been formulated for the management of VC. In this study, we integrated the treatment regimen of the Danlian-Tongmai (DLTM) formula, a traditional Chinese medicine (TCM) with anti-diabetic VC (anti-DVC) effects with intermittent fasting (IF), and established the Chinese medicine and intermittent fasting integration therapy (CMIT). CMIT synergistically enhanced the regulation of calcium-phosphorus homeostasis and vascular repair, and demonstrated significantly greater efficacy than DLTM or IF monotherapy in inhibiting calcium deposition and osteogenic differentiation both in vivo and in vitro. Transcriptomic sequencing revealed that the miR21-5p/Tpm1 axis mediated the anti-calcification effect of CMIT. MiR21-5p promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating Tpm1, while CMIT inhibited such processes. In conclusion, this study demonstrated that CMIT inhibited the osteogenic differentiation of VSMC and restored its contractile phenotype by inhibiting the activation of the miR21-5p/Tpm1 axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.
{"title":"Chinese medicine and intermittent fasting integration therapy attenuate diabetic vascular calcification via miR21-5p/Tpm1-mediated osteogenic differentiation of VSMCs","authors":"Wenting Wang , Yanfei Liu , Yiwen Li , Qian Xu , Mengmeng Zhu , Jing Cui , Yue Liu","doi":"10.1016/j.apsb.2025.11.016","DOIUrl":"10.1016/j.apsb.2025.11.016","url":null,"abstract":"<div><div>Vascular calcification (VC) is a marker of substantial vascular damage in patients with diabetes and has been recognized as a predictor of cardiovascular events and all-cause mortality. To date, no effective therapeutic strategy has been formulated for the management of VC. In this study, we integrated the treatment regimen of the Danlian-Tongmai (DLTM) formula, a traditional Chinese medicine (TCM) with anti-diabetic VC (anti-DVC) effects with intermittent fasting (IF), and established the Chinese medicine and intermittent fasting integration therapy (CMIT). CMIT synergistically enhanced the regulation of calcium-phosphorus homeostasis and vascular repair, and demonstrated significantly greater efficacy than DLTM or IF monotherapy in inhibiting calcium deposition and osteogenic differentiation both <em>in vivo</em> and <em>in vitro</em>. Transcriptomic sequencing revealed that the <em>miR21-5p</em>/<em>Tpm1</em> axis mediated the anti-calcification effect of CMIT. <em>MiR21-5p</em> promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating <em>Tpm1</em>, while CMIT inhibited such processes. In conclusion, this study demonstrated that CMIT inhibited the osteogenic differentiation of VSMC and restored its contractile phenotype by inhibiting the activation of the <em>miR21-5p</em>/<em>Tpm1</em> axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 352-370"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941527","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}
Osteoarthritis (OA) presents significant therapeutic challenges due to the irreversible cartilage loss driven by chondrocyte metabolic imbalance and a severe inflammatory microenvironment. Conventional treatments are limited by poor chondrocyte-targeting and ineffectiveness of single-target medication. Here, we develop an anti-inflammatory neutrophil-derived microvesicle (MV)-based gene therapy for OA treatment, which leverages the intrinsic cartilage-penetrating capabilities of MVs to improve the targeted delivery of microRNA-140-5p (miR140) to chondrocytes, and the synergistic effect of anti-inflammatory MVs and miR140 to dual modulate the metabolic homeostasis of chondrocytes and the inflamed microenvironment. We demonstrate that miR140@MVs not only alleviate synovial inflammation via reprogramming the phenotypes of macrophages and adsorbing inflammatory factors, but also restore normal cartilage thickness in a destabilized medial meniscus mouse model due to the rebuilt metabolic homeostasis of chondrocytes, thus gaining a remarkable therapeutic effect up to 28 days. This study provides an immuno-stimulation method for production of anti-inflammatory MVs, and puts forward a safe and effective MVs-based miRNA system for treatment of joint-related diseases.
{"title":"Dual metabolic-inflammation modulation in MicroRNA@neutrophil-derived microvesicles achieve robust osteoarthritis therapy","authors":"Yijun Chen, Yongbin Wang, Ruonan Yan, Yichen Liu, Yupeng Dai, Lingjing Xue, Caoyun Ju, Can Zhang","doi":"10.1016/j.apsb.2025.09.020","DOIUrl":"10.1016/j.apsb.2025.09.020","url":null,"abstract":"<div><div>Osteoarthritis (OA) presents significant therapeutic challenges due to the irreversible cartilage loss driven by chondrocyte metabolic imbalance and a severe inflammatory microenvironment. Conventional treatments are limited by poor chondrocyte-targeting and ineffectiveness of single-target medication. Here, we develop an anti-inflammatory neutrophil-derived microvesicle (MV)-based gene therapy for OA treatment, which leverages the intrinsic cartilage-penetrating capabilities of MVs to improve the targeted delivery of microRNA-140-5p (miR140) to chondrocytes, and the synergistic effect of anti-inflammatory MVs and miR140 to dual modulate the metabolic homeostasis of chondrocytes and the inflamed microenvironment. We demonstrate that miR140@MVs not only alleviate synovial inflammation <em>via</em> reprogramming the phenotypes of macrophages and adsorbing inflammatory factors, but also restore normal cartilage thickness in a destabilized medial meniscus mouse model due to the rebuilt metabolic homeostasis of chondrocytes, thus gaining a remarkable therapeutic effect up to 28 days. This study provides an immuno-stimulation method for production of anti-inflammatory MVs, and puts forward a safe and effective MVs-based miRNA system for treatment of joint-related diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"16 1","pages":"Pages 423-443"},"PeriodicalIF":14.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941531","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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