Acta Pharmaceutica Sinica. B最新文献_第10页

Exemplifying interspecies variation of liposome in vivo fat e by the effects of anti-PEG antibodies 通过抗 PEG 抗体的影响体现脂质体体内脂肪 e 的种间差异

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-05 DOI: 10.1016/j.apsb.2024.07.009

Ercan Wu, Juan Guan, Yifei Yu, Shiqi Lin, Tianhao Ding, Yuxiu Chu, Feng Pan, Mengyuan Liu, Yang Yang, Zui Zhang, Jian Zhang, Changyou Zhan, Jun Qian

{"title":"Exemplifying interspecies variation of liposome in vivo fat e by the effects of anti-PEG antibodies","authors":"Ercan Wu, Juan Guan, Yifei Yu, Shiqi Lin, Tianhao Ding, Yuxiu Chu, Feng Pan, Mengyuan Liu, Yang Yang, Zui Zhang, Jian Zhang, Changyou Zhan, Jun Qian","doi":"10.1016/j.apsb.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.apsb.2024.07.009","url":null,"abstract":"The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) was much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by antiPEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"12 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945623","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

Discovery of novel small molecules targeting hepatitis B virus core protein from marine natural products with HiBiT-based high-throughput screening 利用基于 HiBiT 的高通量筛选，从海洋天然产物中发现靶向乙型肝炎病毒核心蛋白的新型小分子化合物

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-03 DOI: 10.1016/j.apsb.2024.07.019

Chao Huang, Yang Jin, Panpan Fu, Kongying Hu, Mengxue Wang, Wenjing Zai, Ting Hua, Xinluo Song, Jianyu Ye, Yiqing Zhang, Gan Luo, Haiyu wang, Jiangxia Liu, Jieliang Chen, Xuwen Li, Zhenghong Yuan

{"title":"Discovery of novel small molecules targeting hepatitis B virus core protein from marine natural products with HiBiT-based high-throughput screening","authors":"Chao Huang, Yang Jin, Panpan Fu, Kongying Hu, Mengxue Wang, Wenjing Zai, Ting Hua, Xinluo Song, Jianyu Ye, Yiqing Zhang, Gan Luo, Haiyu wang, Jiangxia Liu, Jieliang Chen, Xuwen Li, Zhenghong Yuan","doi":"10.1016/j.apsb.2024.07.019","DOIUrl":"https://doi.org/10.1016/j.apsb.2024.07.019","url":null,"abstract":"Due to the limitations of current anti-HBV therapies, the HBV core (HBc) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound , a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound (IC = 0.24 μmol/L. Furthermore, was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 for anti-HBV activity. Treatment with in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"25 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945670","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

Drug discovery targeting thyroid hormone receptor β (THRβ) for the treatment of liver diseases and other medical indications 针对甲状腺激素受体 β (THRβ) 的药物研发，用于治疗肝脏疾病和其他医疗适应症

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-02 DOI: 10.1016/j.apsb.2024.07.025

Kean Wang, Feiyang Chen, Jiang Wang, Hong Liu

引用次数: 0

Advancements and challenges in immunocytokines: A new arsenal against cancer 免疫细胞因子的进步与挑战：抗击癌症的新武器

IF 14.5 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-02 DOI: 10.1016/j.apsb.2024.07.024

Wenqiang Shi, Nan Liu, Huili Lu

{"title":"Advancements and challenges in immunocytokines: A new arsenal against cancer","authors":"Wenqiang Shi, Nan Liu, Huili Lu","doi":"10.1016/j.apsb.2024.07.024","DOIUrl":"https://doi.org/10.1016/j.apsb.2024.07.024","url":null,"abstract":"Immunocytokines, employing targeted antibodies to concentrate cytokines at tumor sites, have shown potential advantages such as prolonged cytokine half-lives, mitigated adverse effects, and synergistic antitumor efficacy from both antibody and cytokine components. First, we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications. Notably, anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8 T cells and reinvigorate them to elicit robust antitumor immune responses. Then, we focus on their molecular structures and action mechanisms, striving to elucidate the correlations between diverse molecular structures and their antitumor efficacy. Moreover, our exploration extends to the realm of novel cytokines, including IL-10, IL-18, and IL-24, unraveling their potential in the construction of immunocytokines. However, safety concerns remain substantial barriers to immunocytokines' development. To address this challenge, we explore potential strategies, such as cytokine engineering and prodrug design, which can foster next-generation immunocytokines development. Overall, this review concentrates on the design of molecular structures in immunocytokines, underscoring the direction and focus of ongoing efforts to improve safety profiles while maximizing therapeutic efficacy.","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"95 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945665","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

Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy 药物发现中组合库的编码和显示技术：从生物学到治疗学的时代即将到来

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.04.006

{"title":"Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy","authors":"","doi":"10.1016/j.apsb.2024.04.006","DOIUrl":"10.1016/j.apsb.2024.04.006","url":null,"abstract":"<div><p>Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation. We discuss the progress of novel targeted therapeutic agents, covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear, monocyclic, and bicyclic peptides, in addition to antibodies. We also address the pending challenges and future prospects of drug discovery, including the size of screening libraries, advantages and disadvantages of the technology, clinical translational potential, and market space. This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 8","pages":"Pages 3362-3384"},"PeriodicalIF":14.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524001345/pdfft?md5=e833fefe209f252d55436a3fb425667d&pid=1-s2.0-S2211383524001345-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613734","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

Lyophilized lymph nodes: A paradigm shift in CAR T-cell delivery for solid tumor therapy 冻干淋巴结：用于实体瘤治疗的 CAR T 细胞递送模式转变

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.05.023

引用次数: 0

Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells 树枝状纳米药物通过扰乱癌症相关成纤维细胞的新陈代谢，促进化疗免疫疗法的深入渗透并激活免疫细胞的功能

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.03.010

{"title":"Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells","authors":"","doi":"10.1016/j.apsb.2024.03.010","DOIUrl":"10.1016/j.apsb.2024.03.010","url":null,"abstract":"<div><p>Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, <em>α</em>-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4<sup>+</sup> T cell population, reducing CD4<sup>+</sup> and CD8<sup>+</sup> T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 8","pages":"Pages 3680-3696"},"PeriodicalIF":14.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524000923/pdfft?md5=e3ca7ec0b9522d3542cf3fc877195660&pid=1-s2.0-S2211383524000923-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125202","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

Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation 艾兰西酮通过抑制 JUN 依赖性 MEOX1 激活改善肺纤维化

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.04.013

{"title":"Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation","authors":"","doi":"10.1016/j.apsb.2024.04.013","DOIUrl":"10.1016/j.apsb.2024.04.013","url":null,"abstract":"<div><p>Pulmonary fibrosis poses a significant health threat with very limited therapeutic options available. In this study, we reported the enhanced expression of mesenchymal homobox 1 (MEOX1) in pulmonary fibrosis patients, especially in their fibroblasts and endothelial cells, and confirmed MEOX1 as a central orchestrator in the activation of profibrotic genes. By high-throughput screening, we identified Ailanthone (AIL) from a natural compound library as the first small molecule capable of directly targeting and suppressing MEOX1. AIL demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-<em>β</em>1 (TGF-<em>β</em>1). In an animal model of bleomycin-induced pulmonary fibrosis, AIL effectively mitigated the fibrotic process and restored respiratory functions. Mechanistically, AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1, thereby inhibiting MEOX1 expression and activity. In summary, our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in fibrosis. Moreover, we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis, specifically through the suppression of JUN-dependent MEOX1 activation.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 8","pages":"Pages 3543-3560"},"PeriodicalIF":14.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524001424/pdfft?md5=bdcbec35a606de8e85858f7564e70bb3&pid=1-s2.0-S2211383524001424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140762306","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

The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications 植物三萜类和类固醇在胆汁酸代谢、转运和信号传递中的作用：药理学和毒理学意义

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.04.027

{"title":"The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications","authors":"","doi":"10.1016/j.apsb.2024.04.027","DOIUrl":"10.1016/j.apsb.2024.04.027","url":null,"abstract":"<div><p>Bile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 8","pages":"Pages 3385-3415"},"PeriodicalIF":14.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524001680/pdfft?md5=5ea1569a240e6ead8fe2bb532d029a15&pid=1-s2.0-S2211383524001680-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140938813","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

Mitophagy and cGAS–STING crosstalk in neuroinflammation 神经炎症中的有丝分裂和 cGAS-STING 相互影响

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-08-01 DOI: 10.1016/j.apsb.2024.05.012

{"title":"Mitophagy and cGAS–STING crosstalk in neuroinflammation","authors":"","doi":"10.1016/j.apsb.2024.05.012","DOIUrl":"10.1016/j.apsb.2024.05.012","url":null,"abstract":"<div><p>Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response. Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS–STING pathway. We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions, primarily through the accumulation of damaged mitochondria, which activates the cGAS–STING pathway. This activation prompts the production of pro-inflammatory cytokines, exacerbating neuroinflammation. This review emphasizes the interaction between mitophagy and the cGAS–STING pathways. Effective mitophagy may suppress the cGAS–STING pathway, offering protection against neuroinflammation. Conversely, impaired mitophagy may activate the cGAS–STING pathway, leading to chronic neuroinflammation. Additionally, we explored how this interaction influences neurodegenerative disorders, suggesting a common mechanism underlying these diseases. In conclusion, there is a need for additional targeted research to unravel the complexities of mitophagy–cGAS–STING interactions and their role in neurodegeneration. This review highlights potential therapies targeting these pathways, potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions. This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.</p></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 8","pages":"Pages 3327-3361"},"PeriodicalIF":14.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211383524001904/pdfft?md5=9065b109f686d40cb2f2716e867bf812&pid=1-s2.0-S2211383524001904-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141055546","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