Acta Pharmaceutica Sinica. B最新文献

{"title":"Unveiling nonribosomal peptide synthetases from the ergot fungus Claviceps purpurea involved in the formation of diverse ergopeptines","authors":"Jing-Jing Chen,&nbsp;Ting Gong,&nbsp;Wei-Bo Wang,&nbsp;Tian-Jiao Chen,&nbsp;Jin-Ling Yang,&nbsp;Ping Zhu","doi":"10.1016/j.apsb.2025.03.022","DOIUrl":"10.1016/j.apsb.2025.03.022","url":null,"abstract":"<div><div>Ergopeptines or their derivatives are widely used for treating neurodegenerative and cerebrovascular diseases. The nonribosomal peptide synthetase—<span>d</span>-lysergyl peptide synthetase A (LPSA) determines ergopeptine formation but the detailed mechanism remains to be elucidated. Here, we characterized two LPSAs from <em>Claviceps purpurea</em> Cp-1 strain through heterologous expression in <em>Aspergillus nidulans</em> feeding with <span>d</span>-lysergic acid. We proved that Cp-LPSA1 catalyzed the formation of ergocornine, <em>α</em>-ergocryptine, and <em>β</em>-ergocryptine, precisely controlled by the substrate specificity of its three modules. Cp-LPSA2 was initially inactive but could be restored to catalyze <em>α</em>-ergosine formation. Using this platform, we validated that P1-LPSA1 and P1-LPSA2 from the reported <em>C. purpurea</em> P1 strain catalyzed ergotamine and <em>α</em>-ergocryptine formation, respectively. Typically, the non-ribosomal peptide codes implicated in every module of the LPSAs were defined and elucidated, in which certain key residues could play a switched role for substrate specificity and product interconversion. By constructing chimeric LPSAs through module assembly, the production of the desired ergopeptines was achieved. Notably, 1.46 mg/L of <em>α</em>-ergocryptine and 1.09 mg/L of ergotamine were produced respectively by mixed-culture of <em>C. paspali</em> No. 24 (fermentation supernatant) and the recombinants of <em>A. nidulans</em>. Our findings provide insights into the biosynthetic mechanism of ergopeptines and lay a foundation for directed ergopeptine biosynthesis.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3321-3337"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472221","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}

{"title":"Mechanism of Alzheimer's disease treatment by sound and light stimulation","authors":"Lixuan Ren ,&nbsp;Xiwen Ma ,&nbsp;Jianping Ye","doi":"10.1016/j.apsb.2025.03.031","DOIUrl":"10.1016/j.apsb.2025.03.031","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3346-3348"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472224","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}

{"title":"Editorial of the special column on nanomedicines for tumor microenvironment modulation","authors":"Huile Gao ,&nbsp;Feihu Wang ,&nbsp;Yang Shi","doi":"10.1016/j.apsb.2025.05.027","DOIUrl":"10.1016/j.apsb.2025.05.027","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2816-2817"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472423","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}

{"title":"Advancements in CRISPR/Cas systems for disease treatment","authors":"Yangsong Xu,&nbsp;Hao Le,&nbsp;Qinjie Wu,&nbsp;Ning Wang,&nbsp;Changyang Gong","doi":"10.1016/j.apsb.2025.05.007","DOIUrl":"10.1016/j.apsb.2025.05.007","url":null,"abstract":"<div><div>The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system present in most bacteria and archaea, protecting them from infection by exogenous genetic elements. Due to its simplicity, cost-effectiveness, and precise gene editing capabilities, CRISPR/Cas technology has emerged as a promising tool for treating diseases. The continuous refinement of derivative systems has further broadened its scope in disease treatment. Nevertheless, the heterogeneous physiopathological nature of diseases and variations in disease onset sites pose significant challenges for <em>in vivo</em> applications of CRISPR systems. The efficiency of CRISPR systems in disease treatment is directly influenced by the performance of the delivery system. Additionally, concerns such as off-target effects present crucial hurdles in the clinical implementation of CRISPR systems. This review provides a comprehensive overview of the development of CRISPR systems, vector technologies, and their applications in disease treatment, while also addressing the challenges encountered in clinical settings. Furthermore, future research directions are outlined to pave the way for advancements in CRISPR-based therapies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2818-2844"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471801","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}

{"title":"An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation","authors":"Xinxing Li ,&nbsp;Wenxin Ding ,&nbsp;Yan Lu ,&nbsp;Haiyan Zhu ,&nbsp;Weilian Bao ,&nbsp;Yang Liu ,&nbsp;Jiaren Lyu ,&nbsp;Lishuang Zhou ,&nbsp;Hong Li ,&nbsp;Jiyang Li ,&nbsp;Daofeng Chen","doi":"10.1016/j.apsb.2025.04.008","DOIUrl":"10.1016/j.apsb.2025.04.008","url":null,"abstract":"<div><div>The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from <em>Houttuynia cordata</em> (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without <em>in vitro</em> antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant <em>Staphylococcus aureus</em> (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut–lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut–lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral–bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3073-3091"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471858","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}

{"title":"Submicron-sized superantigen biomimetic liposomes: enhanced lung accumulation and synergistic chemoimmunotherapy","authors":"Fan Jia,&nbsp;Siyuan Peng,&nbsp;Wenhao Wang,&nbsp;Xin Pan","doi":"10.1016/j.apsb.2025.05.032","DOIUrl":"10.1016/j.apsb.2025.05.032","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3349-3350"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472225","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}

{"title":"Author correction to “The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery” [Acta Pharm Sin B 12 (2022) 1460–1472]","authors":"Jingyi Li ,&nbsp;Yaqi Zhang ,&nbsp;Miaorong Yu ,&nbsp;Aohua Wang ,&nbsp;Yu Qiu ,&nbsp;Weiwei Fan ,&nbsp;Lars Hovgaard ,&nbsp;Mingshi Yang ,&nbsp;Yiming Li ,&nbsp;Rui Wang ,&nbsp;Xiuying Li ,&nbsp;Yong Gan","doi":"10.1016/j.apsb.2025.04.015","DOIUrl":"10.1016/j.apsb.2025.04.015","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Page 3353"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472275","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}

{"title":"Submicron-sized superantigen biomimetic liposomes with highly efficient pulmonary accumulation to remodel local immune microenvironment for cancer chemoimmunotherapy","authors":"Bochuan Yuan ,&nbsp;Feng Zhang ,&nbsp;Qiucheng Yan ,&nbsp;Wanmei Wang ,&nbsp;Zhangyu Li ,&nbsp;Lina Du ,&nbsp;Yiguang Jin ,&nbsp;Fei Xie","doi":"10.1016/j.apsb.2025.03.019","DOIUrl":"10.1016/j.apsb.2025.03.019","url":null,"abstract":"<div><div>Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the <em>Escherichia coli</em> system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 2900-2914"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471780","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}

{"title":"Ablation of macrophage transcriptional factor FoxO1 protects against ischemia–reperfusion injury-induced acute kidney injury","authors":"Yao He ,&nbsp;Xue Yang ,&nbsp;Chenyu Zhang ,&nbsp;Min Deng ,&nbsp;Bin Tu ,&nbsp;Qian Liu ,&nbsp;Jiaying Cai ,&nbsp;Ying Zhang ,&nbsp;Li Su ,&nbsp;Zhiwen Yang ,&nbsp;Hongfeng Xu ,&nbsp;Zhongyuan Zheng ,&nbsp;Qun Ma ,&nbsp;Xi Wang ,&nbsp;Xuejun Li ,&nbsp;Linlin Li ,&nbsp;Long Zhang ,&nbsp;Yongzhuo Huang ,&nbsp;Lu Tie","doi":"10.1016/j.apsb.2025.04.009","DOIUrl":"10.1016/j.apsb.2025.04.009","url":null,"abstract":"<div><div>Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia–reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1’s pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3107-3124"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472274","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}

{"title":"Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system","authors":"Jizhuang Ma ,&nbsp;Keda Zhang ,&nbsp;Wenhan Li ,&nbsp;Yu Ding ,&nbsp;Yongfeng Chen ,&nbsp;Xiaoyu Huang ,&nbsp;Tong Yu ,&nbsp;Di Song ,&nbsp;Haoran Niu ,&nbsp;Huichao Xie ,&nbsp;Tianzhi Yang ,&nbsp;Xiaoyun Zhao ,&nbsp;Xinggang Yang ,&nbsp;Pingtian Ding","doi":"10.1016/j.apsb.2025.03.032","DOIUrl":"10.1016/j.apsb.2025.03.032","url":null,"abstract":"<div><div>Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of “vascular damage and plasmin (PLA) system inhibition.” We intended to construct a novel cationic surfactant (AEO_x-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEO_x) by ester bonds. AEO_x-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEO_x-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEO_x-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEO_x-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 6","pages":"Pages 3291-3304"},"PeriodicalIF":14.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472301","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}