Acta Pharmaceutica Sinica. B最新文献_第2页

Sympathetic nerve activity in obesity-associated insulin resistance 肥胖相关胰岛素抵抗的交感神经活动

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.01.018

Shuchou Xia , Huili Wu , Jianping Ye

引用次数: 0

Reshaping antivenom therapy: A triple-synergy strategy featuring broadly neutralizing antibodies and a small-molecule PLA2 inhibitor 重塑抗蛇毒血清治疗：具有广泛中和抗体和小分子PLA2抑制剂的三重协同策略

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.019

Yangyihua Zhou , Ning Shi , Xiang Gao , Longlong Luo

引用次数: 0

CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury CMD-OPT模型能够发现一种有效的、选择性的RIPK2抑制剂，作为治疗急性肝损伤的临床前候选药物

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.003

Yong Chen , Xue Yuan , Wei Yan , Yurong Zou , Haoche Wei , Yuhan Wei , Minghai Tang , Yulian Chen , Ziyan Ma , Tao Yang , Kongjun Liu , Baojian Xiong , Xiuying Hu , Jianhong Yang , Lijuan Chen

{"title":"CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury","authors":"Yong Chen , Xue Yuan , Wei Yan , Yurong Zou , Haoche Wei , Yuhan Wei , Minghai Tang , Yulian Chen , Ziyan Ma , Tao Yang , Kongjun Liu , Baojian Xiong , Xiuying Hu , Jianhong Yang , Lijuan Chen","doi":"10.1016/j.apsb.2025.05.003","DOIUrl":"10.1016/j.apsb.2025.05.003","url":null,"abstract":"<div><div>Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-<em>κ</em>B signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound <strong>RP20</strong>, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning <strong>RP20</strong> as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3708-3724"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572183","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

Immune organoid for cancer immunotherapy 用于癌症免疫治疗的免疫类器官

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.031

Xiao-He Wang, Wu-Yin Wang, Zhi-Jun Sun

{"title":"Immune organoid for cancer immunotherapy","authors":"Xiao-He Wang, Wu-Yin Wang, Zhi-Jun Sun","doi":"10.1016/j.apsb.2025.04.031","DOIUrl":"10.1016/j.apsb.2025.04.031","url":null,"abstract":"<div><div>Cancer immunotherapy, which harnesses the patient's own immune system to target malignant cells, has shown remarkable promise in reducing tumor burden and extending survival. However, the complex tumor microenvironment (TME) limits therapeutic benefits to a subset of patients, making it challenging to develop accurate <em>in vitro</em> models for drug response prediction, drug discovery, and personalized medicine. Organoids, three-dimensional (3D) “mini-organs” derived from individual patients that faithfully recapitulate the structural, molecular, and gene expression profiles of primary tumors along with their complex TME <em>in vitro</em>, have emerged as powerful tools for patient-specific drug screening and therapeutic strategy development. Their versatility has led to widespread adoption across both clinical and basic cancer research. However, a key limitation of traditional organoid models is their lack of immune system components. Recent years have seen significant efforts to address this challenge through the integration of immune cells with organoids, aiming to create more physiologically relevant models. This review describes 3D culture methods for immunocompetent organoids, explores organoid–immune cell interactions, and discusses their applications in cancer immunotherapy and drug screening, along with recent advances in related clinical studies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3419-3435"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572732","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

Enzyme-independent functions of HDAC3 in the adult heart 成人心脏中HDAC3的酶非依赖性功能

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.002

Sichong Qian , Chen Zhang , Wenbo Li , Shiyang Song , Guanqiao Lin , Zixiu Cheng , Wenjun Zhou , Huiqi Yin , Yueli Wang , Haiyang Li , Ying H. Shen , Zheng Sun

{"title":"Enzyme-independent functions of HDAC3 in the adult heart","authors":"Sichong Qian , Chen Zhang , Wenbo Li , Shiyang Song , Guanqiao Lin , Zixiu Cheng , Wenjun Zhou , Huiqi Yin , Yueli Wang , Haiyang Li , Ying H. Shen , Zheng Sun","doi":"10.1016/j.apsb.2025.05.002","DOIUrl":"10.1016/j.apsb.2025.05.002","url":null,"abstract":"<div><div>The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33–70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2<em>β</em> (LAP2<em>β</em>). Tethering LAP2<em>β</em> to the HDAC3 Δ33–70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3561-3574"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572774","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

Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury 生物材料及干细胞/外泌体治疗外伤性脑损伤的研究进展

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.010

Wenya Chi , Yingying He , Shuisheng Chen , Lingyi Guo , Yan Yuan , Rongjie Li , Ruiyao Liu , Dairan Zhou , Jianzhong Du , Tao Xu , Yuan Yu

{"title":"Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury","authors":"Wenya Chi , Yingying He , Shuisheng Chen , Lingyi Guo , Yan Yuan , Rongjie Li , Ruiyao Liu , Dairan Zhou , Jianzhong Du , Tao Xu , Yuan Yu","doi":"10.1016/j.apsb.2025.05.010","DOIUrl":"10.1016/j.apsb.2025.05.010","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood–brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3511-3544"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572773","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

Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells 单细胞RNA测序显示参白解毒汤通过调节TMEM131-TNF信号通路介导的免疫抑制性树突状细胞分化，延缓结直肠肿瘤发生

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.05.013

Yuquan Tao , Yinuo Ma , Limei Gu , Ye Zhang , Qinchang Zhang , Lisha Zhou , Jie Pan , Meng Shen , Xuefei Zhuang , Linmei Pan , Weixing Shen , Chengtao Yu , Dan Dong , Dong Zhang , Tingsheng Ling , Yang Sun , Haibo Cheng

{"title":"Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells","authors":"Yuquan Tao , Yinuo Ma , Limei Gu , Ye Zhang , Qinchang Zhang , Lisha Zhou , Jie Pan , Meng Shen , Xuefei Zhuang , Linmei Pan , Weixing Shen , Chengtao Yu , Dan Dong , Dong Zhang , Tingsheng Ling , Yang Sun , Haibo Cheng","doi":"10.1016/j.apsb.2025.05.013","DOIUrl":"10.1016/j.apsb.2025.05.013","url":null,"abstract":"<div><div>Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in <em>Apc</em><sup>Min/+</sup> mice and clinical patients. There was a marked accumulation of CCL22<sup>+</sup> dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22<sup>+</sup> DCs, which may represent “exhausted DCs”. Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22<sup>+</sup> DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3545-3560"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572775","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 platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy 在黑色素瘤免疫治疗中增强肿瘤渗透和延长循环的工程血小板衍生外泌体球

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.013

Jian Zhao , Xinyan Lv , Qi Lu , Kaiyuan Wang , Lili Du , Xiaoyuan Fan , Fei Sun , Fengxiang Liu , Zhonggui He , Hao Ye , Jin Sun

{"title":"Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy","authors":"Jian Zhao , Xinyan Lv , Qi Lu , Kaiyuan Wang , Lili Du , Xiaoyuan Fan , Fei Sun , Fengxiang Liu , Zhonggui He , Hao Ye , Jin Sun","doi":"10.1016/j.apsb.2025.04.013","DOIUrl":"10.1016/j.apsb.2025.04.013","url":null,"abstract":"<div><div>Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells’ large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked <em>via</em> pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3756-3766"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572186","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

Extracellular vesicles as biomarkers and drug delivery systems for tumor 细胞外囊泡作为肿瘤的生物标志物和药物传递系统

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.033

Xue Wang , Wenjing Chen , Wei Zeng , Kuanhan Feng , Yu Zheng , Ping Wang , Fucai Chen , Wen Zhang , Liuqing Di , Ruoning Wang

引用次数: 0

Discovery of Yersinia LcrV as a novel biased agonist of formyl peptide receptor 1 to bi-directionally modulate intracellular kinases in triple-negative breast cancer 发现耶尔森菌LcrV作为甲酰基肽受体1的新型偏倚激动剂双向调节三阴性乳腺癌细胞内激酶

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-07-01 DOI: 10.1016/j.apsb.2025.04.030

Yunjun Ge , Huiwen Guan , Ting Li , Jie Wang , Liang Ying , Shuhui Guo , Jinjian Lu , Richard D. Ye , Guosheng Wu

{"title":"Discovery of Yersinia LcrV as a novel biased agonist of formyl peptide receptor 1 to bi-directionally modulate intracellular kinases in triple-negative breast cancer","authors":"Yunjun Ge , Huiwen Guan , Ting Li , Jie Wang , Liang Ying , Shuhui Guo , Jinjian Lu , Richard D. Ye , Guosheng Wu","doi":"10.1016/j.apsb.2025.04.030","DOIUrl":"10.1016/j.apsb.2025.04.030","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that <em>Yersinia pestis</em> LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and <em>β</em>-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3646-3662"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572181","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