Acta Pharmaceutica Sinica. B最新文献

Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects 新一代抗真菌药物：机制、疗效和临床前景

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.013

Xueni Lu , Jianlin Zhou , Yi Ming , Yuan Wang , Ruirui He , Yangyang Li , Lingyun Feng , Bo Zeng , Yanyun Du , Chenhui Wang

{"title":"Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects","authors":"Xueni Lu , Jianlin Zhou , Yi Ming , Yuan Wang , Ruirui He , Yangyang Li , Lingyun Feng , Bo Zeng , Yanyun Du , Chenhui Wang","doi":"10.1016/j.apsb.2025.06.013","DOIUrl":"10.1016/j.apsb.2025.06.013","url":null,"abstract":"<div><div>Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 3852-3887"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863333","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

Blades and barriers: Oral vaccines for conquering cancers and warding off infectious diseases 刀锋和屏障：口服疫苗用于战胜癌症和抵御传染病

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.038

Kun Yang , Jinhua Liu , Yi Zhao , Haiting Xu , Menghang Zu , Baoyi Li , Xiaoxiao Shi , Rui L. Reis , Subhas C. Kundu , Bo Xiao

{"title":"Blades and barriers: Oral vaccines for conquering cancers and warding off infectious diseases","authors":"Kun Yang , Jinhua Liu , Yi Zhao , Haiting Xu , Menghang Zu , Baoyi Li , Xiaoxiao Shi , Rui L. Reis , Subhas C. Kundu , Bo Xiao","doi":"10.1016/j.apsb.2025.05.038","DOIUrl":"10.1016/j.apsb.2025.05.038","url":null,"abstract":"<div><div>Global public health faces substantial challenges from malignant tumors and infectious diseases. Vaccination provides an approach for treating and preventing these diseases. Oral vaccinations are particularly advantageous in disease treatment and prevention due to their non-invasive nature, high patient compliance, convenience, cost-effectiveness, and capacity to stimulate comprehensive and adaptive immune responses. However, the overwhelming majority of oral vaccines remain in experimental development, struggling with clinical and commercial translation due to their suboptimal efficacy. Thus, enhancing scientists’ understanding of the interaction between vaccines and gastrointestinal immune system, creating antigen delivery systems suitable for the gut mucosal environment, developing more potent antigenic epitopes, and using personalized combination therapies are critical for advancing the next generation of oral vaccines. This article explores the fundamental principles and applications of current oral anti-tumor and anti-infective vaccines and discusses considerations necessary for designing future oral vaccines.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 3925-3950"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863335","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

Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression 肝细胞中普遍存在的microRNA-320下调可触发rfx1介导的FGF1抑制，从而加速MASH进展

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.007

Liu Yang , Wenjun Li , Yingfen Chen , Ru Ya , Shengying Qian , Li Liu , Yawen Hao , Qiuhong Zai , Peng Xiao , Seonghwan Hwang , Yong He

{"title":"Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression","authors":"Liu Yang , Wenjun Li , Yingfen Chen , Ru Ya , Shengying Qian , Li Liu , Yawen Hao , Qiuhong Zai , Peng Xiao , Seonghwan Hwang , Yong He","doi":"10.1016/j.apsb.2025.06.007","DOIUrl":"10.1016/j.apsb.2025.06.007","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 <em>in situ</em> hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of <em>Rfx1</em> in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4096-4114"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863818","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

Macrophage DGKζ-mediated phosphatidic acid remodeling aggravates acute liver failure 巨噬细胞dgkζ介导的磷脂酸重塑可加重急性肝衰竭

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.019

Yumeng Miao , Tzuchun Lin , Bianlin Wang , Junyu Xu , Chongxian Li , Zuopeng Li , Xinwen Zhang , Chendong Zhou , Tuerganaili Aji , Minjia Tan , Haji Akber Aisa , Jingya Li

{"title":"Macrophage DGKζ-mediated phosphatidic acid remodeling aggravates acute liver failure","authors":"Yumeng Miao , Tzuchun Lin , Bianlin Wang , Junyu Xu , Chongxian Li , Zuopeng Li , Xinwen Zhang , Chendong Zhou , Tuerganaili Aji , Minjia Tan , Haji Akber Aisa , Jingya Li","doi":"10.1016/j.apsb.2025.06.019","DOIUrl":"10.1016/j.apsb.2025.06.019","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + <span>d</span>-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1<em>β</em> (IL-1<em>β</em>) transcription. Through biotin labeling-mediated pull-down and LC–MS/MS analysis, diacylglycerol kinase <em>ζ</em> (DGK<em>ζ</em>), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGK<em>ζ</em> is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)–inositol 1,4,5-trisphosphate (IP<sub>3</sub>)–Ca<sup>2+</sup> signaling and subsequent janus kinase 2 (JAK2)–signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1<em>β</em> production and liver failure. DGK<em>ζ</em> knockdown/ablation or inhibition significantly impairs the DGK<em>ζ</em>–STAT3–IL-1<em>β</em> pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGK<em>ζ</em> inhibitor and acts against inflammation in a DGK<em>ζ</em>-reliant manner. Taken together, CAM12203 inhibits IL-1<em>β</em> transcription in macrophages by binding to DGK<em>ζ</em> and blocking the DGK<em>ζ</em>–STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGK<em>ζ</em> as a novel therapeutic target.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4078-4095"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863810","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

Rapid discovery of drug-introduced multiple organ dysfunction via NIR-II fluorescent imaging 通过NIR-II荧光成像快速发现药物引入的多器官功能障碍

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.023

Pu Jiang , Ruihu Song , Yue Hu , Xin He , Zewei Zhang , Xuemei Wei , Zhiming Wang , De-an Guo , Hao Chen

{"title":"Rapid discovery of drug-introduced multiple organ dysfunction via NIR-II fluorescent imaging","authors":"Pu Jiang , Ruihu Song , Yue Hu , Xin He , Zewei Zhang , Xuemei Wei , Zhiming Wang , De-an Guo , Hao Chen","doi":"10.1016/j.apsb.2025.06.023","DOIUrl":"10.1016/j.apsb.2025.06.023","url":null,"abstract":"<div><div>The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4285-4299"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863245","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 tumor specific AAV for IL-12 delivery in ovarian cancer immunotherapy 卵巢癌免疫治疗中IL-12传递的工程化肿瘤特异性AAV

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.05.033

Fan Tong , Hanmei Li , Huile Gao , Yuan Li

引用次数: 0

Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells 人工间充质干细胞细胞外囊泡通过靶向重塑脑微血管内皮细胞增强缺血性卒中治疗

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.06.009

Shengnan Li , Wei Lv , Jiangna Xu , Jiaqing Yin , Yuqin Chen , Linfeng Liu , Xiang Cao , Wenjing Li , Zhen Li , Hua Chen , Hongliang Xin

{"title":"Artificial mesenchymal stem cell extracellular vesicles enhanced ischemic stroke treatment through targeted remodeling brain microvascular endothelial cells","authors":"Shengnan Li , Wei Lv , Jiangna Xu , Jiaqing Yin , Yuqin Chen , Linfeng Liu , Xiang Cao , Wenjing Li , Zhen Li , Hua Chen , Hongliang Xin","doi":"10.1016/j.apsb.2025.06.009","DOIUrl":"10.1016/j.apsb.2025.06.009","url":null,"abstract":"<div><div>Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes <em>via</em> the H<sub>II</sub> phase transition of 1,2-dioleoyl<em>-sn-</em>glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 8","pages":"Pages 4248-4264"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863169","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

HomoPROTACKeap1: A new strategy of chemical knockdown of Keap1 for allergic rhinitis 化学敲低Keap1治疗变应性鼻炎的新策略

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/j.apsb.2025.07.032

Xiaofeng Qi

引用次数: 0

Cover Story 封面故事

IF 14.6 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2025-08-01 DOI: 10.1016/S2211-3835(25)00471-X

引用次数: 0

From S-nitrosation targets to drugs: A potential new paradigm in disease treatment 从s -亚硝化靶点到药物：疾病治疗的潜在新范式

IF 14.6 1区医学