Acta Pharmaceutica Sinica. B最新文献_第3页

Strategies for intravesical drug delivery: From bladder physiological barriers and potential transport mechanisms 膀胱内给药策略：从膀胱生理屏障和潜在的运输机制入手

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.07.003

Zheng-an Li , Kai-chao Wen , Ji-heng Liu , Chuan Zhang , Feng Zhang , Feng-qian Li

{"title":"Strategies for intravesical drug delivery: From bladder physiological barriers and potential transport mechanisms","authors":"Zheng-an Li , Kai-chao Wen , Ji-heng Liu , Chuan Zhang , Feng Zhang , Feng-qian Li","doi":"10.1016/j.apsb.2024.07.003","DOIUrl":"10.1016/j.apsb.2024.07.003","url":null,"abstract":"<div><div>Intravesical drug delivery (IDD), as a noninvasive, local pathway of administration, has great clinical significance for bladder diseases, especially bladder cancer. Despite the many advantages of IDD such as enhanced focal drug exposure and avoidance of systemic adverse drug reactions, the effectiveness of drug delivery is greatly challenged by the physiological barriers of the bladder. In this review, the routes and barriers encountered in IDD are first discussed, and attention is paid to the potential internal/mucosal retention and absorption-transport mechanisms of drugs. On this basis, the avoidance, overcoming and utilization of the \"three barriers\" is further emphasized, and current design and fabrication strategies for intravesical drug delivery systems (IDDSs) are described mainly from the perspectives of constructing drug reservoirs, enhancing permeability and targeting, with the hope of providing systematic understanding and inspirations for the research of novel IDDSs and their treatment of bladder diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4738-4755"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141612758","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

Future prospects in clinical translation of inorganic nanoparticles 无机纳米粒子临床转化的未来前景

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.001

Ke Xu , Ying Liu , Chunying Chen

引用次数: 0

Activation of pregnane X receptor sensitizes alcoholic steatohepatitis by transactivating fatty acid binding protein 4 通过转录激活脂肪酸结合蛋白 4，激活孕烷 X 受体使酒精性脂肪性肝炎变得敏感

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.029

Yiwen Zhang , Bingfang Hu , Shaoxing Guan , Pan Li , Yingjie Guo , Pengfei Xu , Yongdong Niu , Yujin Li , Ye Feng , Jiewen Du , Jun Xu , Xiuchen Guan , Jingkai Gu , Haiyan Sun , Min Huang

{"title":"Activation of pregnane X receptor sensitizes alcoholic steatohepatitis by transactivating fatty acid binding protein 4","authors":"Yiwen Zhang , Bingfang Hu , Shaoxing Guan , Pan Li , Yingjie Guo , Pengfei Xu , Yongdong Niu , Yujin Li , Ye Feng , Jiewen Du , Jun Xu , Xiuchen Guan , Jingkai Gu , Haiyan Sun , Min Huang","doi":"10.1016/j.apsb.2024.08.029","DOIUrl":"10.1016/j.apsb.2024.08.029","url":null,"abstract":"<div><div>Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16<em>α</em>-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR–FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4776-4788"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187069","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

Adipose ADM2 ameliorates NAFLD via promotion of ceramide catabolism 脂肪 ADM2 通过促进神经酰胺分解代谢改善非酒精性脂肪肝

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.09.010

Pengcheng Wang , Song-Yang Zhang , YongQiang Dong , Guangyi Zeng , Huiying Liu , Xian Wang , Changtao Jiang , Yin Li

{"title":"Adipose ADM2 ameliorates NAFLD via promotion of ceramide catabolism","authors":"Pengcheng Wang , Song-Yang Zhang , YongQiang Dong , Guangyi Zeng , Huiying Liu , Xian Wang , Changtao Jiang , Yin Li","doi":"10.1016/j.apsb.2024.09.010","DOIUrl":"10.1016/j.apsb.2024.09.010","url":null,"abstract":"<div><div>The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic <em>de novo</em> lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2<em>α</em> was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4883-4898"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706968","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

Systemic and dynamic immune landscape of Omicron-infected subjects treated with Lianhua Qingwen capsules 使用连花清瘟胶囊治疗奥米克龙感染者的全身和动态免疫状况

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.09.011

Shijun Chen , Fuxiang Wang , Yuanlong Lin , Yinyin Xie , Ruihong Zhang , Juan Chen , Niu Qiao , Tong Yin , Yun Tan , Hai Fang , Hongzhou Lu , Zhu Chen , Shanhe Yu , Jiang Zhu , Zhenhua Jia , Saijuan Chen

引用次数: 0

A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression 一种磷酸甘油酸突变酶 1 异源抑制剂可抑制 TAM 介导的结肠癌进展

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.09.007

Cheng Wang , Minghao Zhang , Shunyao Li , Miaomiao Gong , Ming-yu Luo , Mo-cong Zhang , Jing-Hua Zou , Ningxiang Shen , Lu Xu , Hui-min Lei , Ling Bi , Liang Zhu , Zhengting Wang , Hong-zhuan Chen , Lu Zhou , Ying Shen

{"title":"A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression","authors":"Cheng Wang , Minghao Zhang , Shunyao Li , Miaomiao Gong , Ming-yu Luo , Mo-cong Zhang , Jing-Hua Zou , Ningxiang Shen , Lu Xu , Hui-min Lei , Ling Bi , Liang Zhu , Zhengting Wang , Hong-zhuan Chen , Lu Zhou , Ying Shen","doi":"10.1016/j.apsb.2024.09.007","DOIUrl":"10.1016/j.apsb.2024.09.007","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of <em>PGAM1</em> correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8<sup>+</sup> T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4819-4831"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706959","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

Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer 结肠特异性口服脂质体控释用于增强结直肠癌化疗免疫疗法

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.09.015

Mengya Niu , Yihan Pei , Tiantian Jin , Junxiu Li , Liming Bai , Cuixia Zheng , Qingling Song , Hongjuan Zhao , Yun Zhang , Lei Wang

{"title":"Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer","authors":"Mengya Niu , Yihan Pei , Tiantian Jin , Junxiu Li , Liming Bai , Cuixia Zheng , Qingling Song , Hongjuan Zhao , Yun Zhang , Lei Wang","doi":"10.1016/j.apsb.2024.09.015","DOIUrl":"10.1016/j.apsb.2024.09.015","url":null,"abstract":"<div><div>A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable <em>in vivo</em> fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating <em>Clostridium butyricum</em> spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into <em>Clostridium butyricum</em> (CB) and colonized in the colon. Combined with colonic specifically <em>β</em>-glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue <em>via</em> the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead <em>Fusobacterium nucleatum</em> and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8<sup>+</sup> T cells and reactivated robust antitumor immunity.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4977-4993"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706966","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

Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment 通过光诱导混合纳米药物将抗炎疗法和 RNA 干扰结合起来治疗骨关节炎

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.06.009

Li Qiao , Zhiyao Li , Bowen Li , Fu Zhang , Zhuo Yao , Chongzhi Wu , Honglin Tang , Qi Pan , Peihua Shi , Yuan Ping

{"title":"Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment","authors":"Li Qiao , Zhiyao Li , Bowen Li , Fu Zhang , Zhuo Yao , Chongzhi Wu , Honglin Tang , Qi Pan , Peihua Shi , Yuan Ping","doi":"10.1016/j.apsb.2024.06.009","DOIUrl":"10.1016/j.apsb.2024.06.009","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(<em>β</em>-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection <em>in vivo</em>, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 5008-5025"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141528594","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

GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection GPR17 通过杏仁核基底外侧到海马 CA1 腹侧的谷氨酸能投射调节焦虑样行为

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.005

Ruizhe Nie, Xinting Zhou, Jiaru Fu, Shanshan Hu, Qilu Zhang, Weikai Jiang, Yizi Yan, Xian Cao, Danhua Yuan, Yan Long, Hao Hong, Susu Tang

{"title":"GPR17 modulates anxiety-like behaviors via basolateral amygdala to ventral hippocampal CA1 glutamatergic projection","authors":"Ruizhe Nie, Xinting Zhou, Jiaru Fu, Shanshan Hu, Qilu Zhang, Weikai Jiang, Yizi Yan, Xian Cao, Danhua Yuan, Yan Long, Hao Hong, Susu Tang","doi":"10.1016/j.apsb.2024.08.005","DOIUrl":"10.1016/j.apsb.2024.08.005","url":null,"abstract":"<div><div>Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, <em>in vitro</em> electrophysiology recordings, <em>in vivo</em> fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors <em>via</em> BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4789-4805"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186922","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

Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections 以 Gac/Rsm 双组分系统为靶点的新型苯并噻唑衍生物是铜绿假单胞菌感染的抗菌增效剂

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.002

Jun Liu , Wenfu Wu , Jiayi Hu , Siyu Zhao , Yiqun Chang , Qiuxian Chen , Yujie Li , Jie Tang , Zhenmeng Zhang , Xiao Wu , Shumeng Jiao , Haichuan Xiao , Qiang Zhang , Jiarui Du , Jianfu Zhao , Kaihe Ye , Meiyan Huang , Jun Xu , Haibo Zhou , Junxia Zheng , Pinghua Sun

{"title":"Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections","authors":"Jun Liu , Wenfu Wu , Jiayi Hu , Siyu Zhao , Yiqun Chang , Qiuxian Chen , Yujie Li , Jie Tang , Zhenmeng Zhang , Xiao Wu , Shumeng Jiao , Haichuan Xiao , Qiang Zhang , Jiarui Du , Jianfu Zhao , Kaihe Ye , Meiyan Huang , Jun Xu , Haibo Zhou , Junxia Zheng , Pinghua Sun","doi":"10.1016/j.apsb.2024.08.002","DOIUrl":"10.1016/j.apsb.2024.08.002","url":null,"abstract":"<div><div>The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. <em>Pseudomonas aeruginosa</em> infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, <strong>SN12</strong> (IC<sub>50</sub> = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations <em>in vitro</em>. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating <em>P. aeruginosa</em>-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, <strong>SN12</strong> slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that <strong>SN12</strong> significantly augmented the antibacterial effects of three widely used antibiotics—tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)—compared with single-dose antibiotic treatments for <em>P. aeruginosa</em> infection <em>in vivo</em>. The findings of this study suggest the potential of <strong>SN12</strong> as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4934-4961"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186923","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