Acta Pharmaceutica Sinica. B最新文献_第4页

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through β-catenin/CREB interruption 转铁蛋白受体靶向免疫刺激剂通过β-catenin/CREB 干扰光动力免疫疗法治疗转移性肿瘤

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.05.030

{"title":"Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through β-catenin/CREB interruption","authors":"","doi":"10.1016/j.apsb.2024.05.030","DOIUrl":"10.1016/j.apsb.2024.05.030","url":null,"abstract":"<div><p>The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting <em>β</em>-catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between <em>β</em>-catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C–C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524002260/pdfft?md5=bd3d0e528bea4dbf84a885e1aac3c35d&pid=1-s2.0-S2211383524002260-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141274200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy 线粒体代谢阻断纳米辅助剂可逆转免疫耐受微环境，使基于白蛋白的紫杉醇化疗免疫疗法更敏感

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.05.028

{"title":"Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy","authors":"","doi":"10.1016/j.apsb.2024.05.028","DOIUrl":"10.1016/j.apsb.2024.05.028","url":null,"abstract":"<div><p>Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-<em>β</em> dual-inhibitor <em>via</em> inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen <em>in vitro</em>, which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-<em>β</em> in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524002247/pdfft?md5=48f1a87a9755d99b23156aa106fd1108&pid=1-s2.0-S2211383524002247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Jun12682, a potent SARS-CoV-2 papain-like protease inhibitor with exceptional antiviral efficacy in mice Jun12682 是一种强效的 SARS-CoV-2 木瓜蛋白酶样蛋白酶抑制剂，对小鼠具有卓越的抗病毒疗效

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.07.001

引用次数: 0

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation 淫羊藿苷通过抑制 PADI2 介导的中性粒细胞浸润和中性粒细胞胞外陷阱的形成来抑制尿道癌的进展

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.06.029

{"title":"Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation","authors":"","doi":"10.1016/j.apsb.2024.06.029","DOIUrl":"10.1016/j.apsb.2024.06.029","url":null,"abstract":"<div><p>Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524002600/pdfft?md5=052d3d123fc6ac471b1e4968f1b74826&pid=1-s2.0-S2211383524002600-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141549271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity 芦荟大黄素通过调节细胞对游离脂肪酸的敏感性来改变肠内分泌细胞的分化命运，从而促进粘膜愈合

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.05.027

{"title":"Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity","authors":"","doi":"10.1016/j.apsb.2024.05.027","DOIUrl":"10.1016/j.apsb.2024.05.027","url":null,"abstract":"<div><p>The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury. Label retaining cells (LRCs) expressing SRY-box transcription factor 9 (SOX9) promote epithelial repair by replenishing LGR5<sup>+</sup> intestinal stem cells (ISCs). While, LRCs are also considered precursor cells for enteroendocrine cells (EECs) which exacerbate mucosal damage in inflammatory bowel disease (IBD). The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear. In this study, we investigated the effects of a natural anthraquinone called aloe emodin (derived from the Chinese herb rhubarb) on mucosal healing in IBD models. Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9<sup>+</sup> LRCs, thereby promoting mucosal healing. Furthermore, we discovered that aloe emodin acted as an antagonist of free fatty acid receptors (FFAR1), suppressing the FFAR1-mediated G<em>βγ</em>/serine/threonine-protein kinase (AKT) pathway and promoting the translocation of forkhead box protein O1 (FOXO1) into the nucleus, ultimately resulting in the intervention of differentiation fate. These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221138352400220X/pdfft?md5=fe75aa13a31229bbb33ebee804785940&pid=1-s2.0-S221138352400220X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141528596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing cancer nanomedicine with machine learning 利用机器学习推动癌症纳米医学的发展

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.06.018

引用次数: 0

Allosteric regulation of Keap1 by 8β-hydroxy-α-cyclocostunolide for the treatment of acute lung injury 8β-hydroxy-α-cyclocostunolide 对 Keap1 的异位调节用于治疗急性肺损伤

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.06.025

引用次数: 0

Discovery and evaluation of a novel 18F-labeled vasopressin 1a receptor PET ligand with peripheral binding specificity 发现和评估具有外周结合特异性的新型 18F 标记加压素 1a 受体 PET 配体

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.05.033

{"title":"Discovery and evaluation of a novel 18F-labeled vasopressin 1a receptor PET ligand with peripheral binding specificity","authors":"","doi":"10.1016/j.apsb.2024.05.033","DOIUrl":"10.1016/j.apsb.2024.05.033","url":null,"abstract":"<div><p>The arginine-vasopressin (AVP) hormone plays a pivotal role in regulating various physiological processes, such as hormone secretion, cardiovascular modulation, and social behavior. Recent studies have highlighted the V1a receptor as a promising therapeutic target. In-depth insights into V1a receptor-related pathologies, attained through <em>in vivo</em> imaging and quantification in both peripheral organs and the central nervous system (CNS), could significantly advance the development of effective V1a inhibitors. To address this need, we develop a novel V1a-targeted positron emission tomography (PET) ligand, [<sup>18</sup>F]V1A-2303 ([<sup>18</sup>F]<strong>8</strong>), which demonstrates favorable <em>in vitro</em> binding affinity and selectivity for the V1a receptor. Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies, autoradiography, biodistribution assessments. Furthermore, [<sup>18</sup>F]<strong>8</strong> was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity, whole-body distribution, and kinetic properties. Our research indicated [<sup>18</sup>F]<strong>8</strong> as a valuable tool for noninvasively studying V1a receptors in peripheral organs, and as a foundational element for the development of next-generation, brain-penetrant ligands specifically designed for the CNS.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":null,"pages":null},"PeriodicalIF":14.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524002296/pdfft?md5=32b93366e822a62bc8cd622576bed926&pid=1-s2.0-S2211383524002296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Story 封面故事

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/S2211-3835(24)00298-3

引用次数: 0

Unveiling ferroptosis as a promising therapeutic avenue for colorectal cancer and colitis treatment 揭示铁蛋白沉积是治疗结直肠癌和结肠炎的有效途径

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-09-01 DOI: 10.1016/j.apsb.2024.05.025

引用次数: 0