Acta Pharmaceutica Sinica. B最新文献_第7页

PTM-centered therapy in malignant tumors: A new story of colchicine 以ptm为中心的恶性肿瘤治疗：秋水仙碱的新故事

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.045

Min Huang

引用次数: 0

Polysaccharide nanoparticles as potential immune adjuvants: Mechanism and function 多糖纳米颗粒作为潜在的免疫佐剂：机制和功能

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.006

Yuhong Jiang, Shanshan Qi, Canquan Mao

{"title":"Polysaccharide nanoparticles as potential immune adjuvants: Mechanism and function","authors":"Yuhong Jiang, Shanshan Qi, Canquan Mao","doi":"10.1016/j.apsb.2025.03.006","DOIUrl":"10.1016/j.apsb.2025.03.006","url":null,"abstract":"<div><div>Adjuvants as essential ingredients amplify the magnitude and durability of immune responses in various vaccine strategies. Polysaccharides with potent immunoenhancing effects are widely applied as promising vaccine adjuvants, however, they have rarely been licensed for use in human vaccines due to the limitation of their efficacy and safety. Moreover, nanoparticles not only act as antigen drug delivery vectors but also possess intrinsic adjuvant functions, revealing the dual effects of nanoparticles in augmenting antigen-specific immune responses. Intriguingly, nanoparticle forms can enhance the immunostimulatory potency of polysaccharide adjuvants, since polysaccharide nanoparticles exert more excellent adjuvant effects than polysaccharides in initiating humoral, cellular and mucosal immune responses. Emerging evidence has also suggested that multiple immune-related signaling pathways including cGAS–STING, NLRP3, TLRs, cell death or metabolism signaling probably participate in the immunomodulation of polysaccharide nanoparticles, but systemic investigations into the adjuvant mechanism are still inadequate. This review aims to give an updated summary and discussion on the adjuvant function and mechanism of polysaccharide nanoparticles for understanding their superior adjuvant property and effectively utilizing them as potent immune adjuvants in vaccine development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1796-1815"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923350","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

Nano-drug delivery strategies affecting cancer-associated fibroblasts to reduce tumor metastasis 影响癌症相关成纤维细胞的纳米药物递送策略以减少肿瘤转移

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.040

Linghui Zou , Peng Xian , Qing Pu , Yangjie Song , Shuting Ni , Lei Chen , Kaili Hu

{"title":"Nano-drug delivery strategies affecting cancer-associated fibroblasts to reduce tumor metastasis","authors":"Linghui Zou , Peng Xian , Qing Pu , Yangjie Song , Shuting Ni , Lei Chen , Kaili Hu","doi":"10.1016/j.apsb.2025.02.040","DOIUrl":"10.1016/j.apsb.2025.02.040","url":null,"abstract":"<div><div>Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial–mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1841-1868"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923352","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

Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways 微生物代谢物3-吲哚丙酸通过抑制IL-13Rα1相关信号通路，减少肠内胶质细胞胶质化，减轻PD病理

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.029

Meiyu Shang , Jingwen Ning , Caixia Zang , Jingwei Ma , Yang Yang , Zhirong Wan , Jing Zhao , Yueqi Jiang , Qiuzhu Chen , Yirong Dong , Jinrong Wang , Fangfang Li , Xiuqi Bao , Dan Zhang

{"title":"Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways","authors":"Meiyu Shang , Jingwen Ning , Caixia Zang , Jingwei Ma , Yang Yang , Zhirong Wan , Jing Zhao , Yueqi Jiang , Qiuzhu Chen , Yirong Dong , Jinrong Wang , Fangfang Li , Xiuqi Bao , Dan Zhang","doi":"10.1016/j.apsb.2025.02.029","DOIUrl":"10.1016/j.apsb.2025.02.029","url":null,"abstract":"<div><div>Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13R<em>α</em>1 involved cytokine–cytokine receptor interaction pathway, leading to inactivation of downstream JAK1–STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut–brain axis.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2024-2038"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923361","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 chromosome-level Dendrobium moniliforme genome assembly reveals the regulatory mechanisms of flavonoid and carotenoid biosynthesis pathways 染色体水平的石斛基因组组装揭示了类黄酮和类胡萝卜素生物合成途径的调控机制

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.005

Jiapeng Yang , Qiqian Xue , Chao Li , Yingying Jin , Qingyun Xue , Wei Liu , Zhitao Niu , Xiaoyu Ding

{"title":"A chromosome-level Dendrobium moniliforme genome assembly reveals the regulatory mechanisms of flavonoid and carotenoid biosynthesis pathways","authors":"Jiapeng Yang , Qiqian Xue , Chao Li , Yingying Jin , Qingyun Xue , Wei Liu , Zhitao Niu , Xiaoyu Ding","doi":"10.1016/j.apsb.2025.03.005","DOIUrl":"10.1016/j.apsb.2025.03.005","url":null,"abstract":"<div><div><em>Dendrobium moniliforme</em> (<em>D. moniliforme</em>) is a traditional medicinal herb widely cultivated in Asia. Flavonoids, one of the largest groups of secondary metabolites in plants, are significant medicinal components in <em>Dendrobium</em> species. Several subgroups of R2R3-MYB proteins have been validated to directly regulate flavonoid biosynthesis. Using PacBio sequencing technology, we assembled a high-quality chromosome-level <em>D. moniliforme</em> genome with a total length of 1.20 Gb and a contig N50 of 3.97 Mb. The BUSCO assessment of genome annotation was 91.4%. By integrating the genome and transcriptome, we identified biosynthesis pathway enzyme genes related to flavonoids, polysaccharides, carotenoids, and alkaloids. A total of 90 R2R3-MYBs were identified in <em>D. moniliforme</em> and classified into 21 subgroups. Studies on the functions of R2R3-MYB transcription factors revealed that R2R3-MYB in SG6 can up-regulate flavonoid biosynthesis. Various validation experiments, including subcellular localization, transient overexpression, UPLC–MS/MS, HPLC, yeast one-hybrid, and dual-luciferase assays, demonstrated that DMYB69 directly up-regulates the expression of enzyme genes involved in flavonoid biosynthesis, increasing the content of flavonoids such as anthocyanin, flavone, and flavonol. Additionally, DMYB44 was shown to directly up-regulate the expression of carotenoid biosynthesis enzyme genes, thereby increasing carotenoid content. This study provides an essential genome resource and theoretical basis for molecular breeding research in <em>D. moniliforme</em>.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2253-2272"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923523","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

Amyloid-like fibrils derived from β-sheets of gp120 contribute to the neuronal pathology of HIV-associated neurocognitive disorders 源自gp120 β-薄片的淀粉样原纤维与hiv相关神经认知障碍的神经病理有关

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.024

Chan Yang , Ruyu Wang , Chen Cheng , Jiaqi Yu , Kunyu Lu , Haobin Li , Jinshen Wang , Guodong Hu , Hao Yang , Jianfu He , Hao Su , Qingping Zhan , Suiyi Tan , Tong Zhang , Shuwen Liu

引用次数: 0

Feature-based molecular networking (FBMN): An efficient booster for discovering novel natural products or metabolites 基于特征的分子网络（FBMN）：发现新的天然产物或代谢物的有效助推器

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.019

Meiru Han , Huan Xia , Guiyang Xia , Xiaohong Wei , Jinyu Li , Yuzhuo Wu , Sheng Lin

引用次数: 0

Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injury via targeting PCBP2 毛蕊花苷通过靶向PCBP2改善肝细胞铁下垂和肝缺血再灌注损伤

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.03.002

Kexin Jia , Yinhao Zhang , Fanghong Li , Runping Liu , Jianzhi Wu , Jiaorong Qu , Ranyi Luo , Zixi Huang , Zhe Xu , Xiaojiaoyang Li

{"title":"Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injury via targeting PCBP2","authors":"Kexin Jia , Yinhao Zhang , Fanghong Li , Runping Liu , Jianzhi Wu , Jiaorong Qu , Ranyi Luo , Zixi Huang , Zhe Xu , Xiaojiaoyang Li","doi":"10.1016/j.apsb.2025.03.002","DOIUrl":"10.1016/j.apsb.2025.03.002","url":null,"abstract":"<div><div>Hepatic ischemia-reperfusion injury (HIRI) has been considered as an inevitable process of liver transplantation. Hepatocyte ferroptosis is a key factor in HIRI development, yet precise mechanism and potential therapies are still unclear. Here, we demonstrated a strong correlation between hepatocyte ferroptosis and the downregulation of poly(rC)-binding protein (PCBP2), which compromised the stability of antiporter system Xc<sup>–</sup> (consisted of SL3A2/SLC7A11). Besides, inhibiting PCBP2 contributed to facilitating cofactor p300 to enhance the transcriptional activity of HIF1<em>α</em>, leading to the expression and secretion of HMGB1. Then, released HMGB1 from ferroptotic hepatocytes worsened M1 macrophage recruitment and immune response during HIRI. Additionally, acteoside (ACT) was shown to assist PCBP2 in stabilizing the mRNA stability of <em>Slc3a2</em> and <em>Slc7a11</em>, as well as enhance the binding affinity of PCBP2–system Xc<sup>–</sup>. Beyond that, ACT also supported PCBP2 to limit HMGB1-induced M1 macrophage recruitment through imposing restrictions on p300 and HIF1<em>α</em>. Furthermore, specific knockdown of PCBP2 in hepatocytes directly interposed the therapeutic efficacy of ACT on HIRI mice. In conclusion, ACT alleviated hepatocyte ferroptosis and HIRI <em>via</em> promoting PCBP2 to maintain the stability of system Xc<sup>–</sup> and limit HIF1<em>α</em>/p300–HMGB1 signaling. These findings highlight the therapeutic benefits of ACT in treating HIRI and offer insights into innovative therapeutic strategies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2077-2094"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924446","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

CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer cdk1介导的USP37磷酸化调节SND1稳定性并促进结直肠癌的肿瘤发生

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.014

Liang Wu , Can Cheng , Ning Zhao , Liang Zhu , Heng Li , Jingwen Liu , Yang Wu , Xi Chen , Hanhui Yao , Lianxin Liu

{"title":"CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer","authors":"Liang Wu , Can Cheng , Ning Zhao , Liang Zhu , Heng Li , Jingwen Liu , Yang Wu , Xi Chen , Hanhui Yao , Lianxin Liu","doi":"10.1016/j.apsb.2025.02.014","DOIUrl":"10.1016/j.apsb.2025.02.014","url":null,"abstract":"<div><div>Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1–USP37–SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1938-1955"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923356","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

Microneedle delivery platform integrated with Staphylococcus epidermidis-derived extracellular vesicles-based nanoantibiotics for efficient bacterial infection atopic dermatitis treatment 微针给药平台结合表皮葡萄球菌衍生的细胞外囊泡纳米抗生素有效治疗细菌感染特应性皮炎

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-04-01 DOI: 10.1016/j.apsb.2025.02.038

Hong Zhou , Shuting Zhang , Xinxin Liu , Aiping Feng , Siyuan Chen , Wei Liu

{"title":"Microneedle delivery platform integrated with Staphylococcus epidermidis-derived extracellular vesicles-based nanoantibiotics for efficient bacterial infection atopic dermatitis treatment","authors":"Hong Zhou , Shuting Zhang , Xinxin Liu , Aiping Feng , Siyuan Chen , Wei Liu","doi":"10.1016/j.apsb.2025.02.038","DOIUrl":"10.1016/j.apsb.2025.02.038","url":null,"abstract":"<div><div>Due to the difficulty of overcoming the abnormal epidermal barriers and addressing <em>S. aureus</em> infections without disrupting indigenous skin microbiota, effective treatment of bacterial infection atopic dermatitis (AD) remains a significant clinical challenge. Skin microbiota-derived extracellular vesicles (EVs) shows protentional for skin disease treatment, but the lack of antimicrobial activity and limited skin penetration hamper their application in bacterial infection AD treatment. Here, we developed novel nanoantibiotics by loading Lev into <em>S. epidermidis-</em>derived EVs (Lev@SE-EVs), with supreme antimicrobial activity, regulating epidermal immune responses and enhanced epidermal barrier functionality. The nanoantibiotics were further integrated into hyaluronic acid-based microneedle (MN) for efficient transdermal delivery of therapeutic agents and effectively treating bacterial infection in AD. Upon insertion into the skin, the rapidly released Lev@SE-EVs from MN are uptake by <em>S. aureus</em> in a selective manner, fibroblasts, and surrounding immune cells to exert therapeutic effects in the infected dermal layer, resulting in mitigated skin inflammation, reduced <em>S. aureus</em> burden and increased dermis repair. Notably, Lev@SE-EVs induce IL-17A<sup>+</sup> CD8<sup>+</sup> T-cell accumulation in the skin in an unrelated inflammation manner, which may represent heterologous protection. This EVs-integrated MN assisted Lev@SE-EVs to alleviate skin inflammation, repair skin, and provide an effective and safe therapeutic approach for bacterial infection AD treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2197-2216"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923519","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