Acta Pharmaceutica Sinica. B最新文献_第8页

Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis 用于治疗脓毒症的双重警戒素-受体特异性靶向肽系统

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 DOI: 10.1016/j.apsb.2024.08.015

Seok-Jun Mun , Euni Cho , Woo Jin Gil , Seong Jae Kim , Hyo Keun Kim , Yu Seong Ham , Chul-Su Yang

{"title":"Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis","authors":"Seok-Jun Mun , Euni Cho , Woo Jin Gil , Seong Jae Kim , Hyo Keun Kim , Yu Seong Ham , Chul-Su Yang","doi":"10.1016/j.apsb.2024.08.015","DOIUrl":"10.1016/j.apsb.2024.08.015","url":null,"abstract":"<div><div>The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis. In this study, we developed a novel alarmin/receptor-targeting system using a TLR4/MD2/RAGE-blocking peptide (TMR peptide) derived from the HMGB1/PTX3-receptors interacting motifs. The TMR peptide successfully attenuated HMGB1/PTX3- and LPS-mediated inflammatory cytokine production by impairing its interactions with TLR4 and RAGE. Moreover, we developed TMR peptide-conjugated liposomes (TMR-Lipo) to improve the peptide pharmacokinetics. In combination therapy, moderately antibiotic-loaded TMR-Lipo demonstrated a significant therapeutic effect in a mouse model of cecal ligation- and puncture-induced sepsis. The identification of these peptides will pave the way for the development of novel pharmacological tools for sepsis therapy.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"Pages 5451-5463"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186914","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

Cell carriers change the in vivo fate of nanoparticles 细胞载体改变纳米粒子的体内命运

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 DOI: 10.1016/j.apsb.2024.08.011

Xiaotong Li , Jianhua He , Wei He

引用次数: 0

Pretheranostic agents with extraordinaryNIRF/photoacoustic imaging performanceand photothermal oncotherapy efficacy 具有非凡近红外荧光/光声成像性能和光热肿瘤疗法疗效的预theranostic 药剂

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 DOI: 10.1016/j.apsb.2024.07.017

Liu Shi , Zhenzhou Chen , Jiaxin Ou , En Liang , Zhipeng Chen , Qiuyue Fu , Lan Huang , Kui Cheng

{"title":"Pretheranostic agents with extraordinaryNIRF/photoacoustic imaging performanceand photothermal oncotherapy efficacy","authors":"Liu Shi , Zhenzhou Chen , Jiaxin Ou , En Liang , Zhipeng Chen , Qiuyue Fu , Lan Huang , Kui Cheng","doi":"10.1016/j.apsb.2024.07.017","DOIUrl":"10.1016/j.apsb.2024.07.017","url":null,"abstract":"<div><div>Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for <em>in vivo</em> monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm<sup>2</sup>, 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"Pages 5370-5381"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775571","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

Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS 通过纳米槲皮素介导的糖酵解和 OXPHOS杠杆作用，重构巨噬细胞的免疫代谢线路，从而治疗牙周炎

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.07.008

Yi Zhang , Junyu Shi , Jie Zhu , Xinxin Ding , Jianxu Wei , Xue Jiang , Yijie Yang , Xiaomeng Zhang , Yongzhuo Huang , Hongchang Lai

{"title":"Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS","authors":"Yi Zhang , Junyu Shi , Jie Zhu , Xinxin Ding , Jianxu Wei , Xue Jiang , Yijie Yang , Xiaomeng Zhang , Yongzhuo Huang , Hongchang Lai","doi":"10.1016/j.apsb.2024.07.008","DOIUrl":"10.1016/j.apsb.2024.07.008","url":null,"abstract":"<div><div>Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (<em>i.e.</em>, from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1<em>β</em> and TNF-<em>α</em>) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis <em>via</em> immunometabolic rewiring.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 5026-5036"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186919","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

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 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 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":"10.1016/j.apsb.2024.07.024","url":null,"abstract":"<div><div>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<sup>+</sup> 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.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4649-4664"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum to “Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis” [Acta Pharm Sin B 14 (2024) 3493–3512] 苯丙氨酸剥夺通过扰动内质网稳态抑制多发性骨髓瘤进展》的勘误 [Acta Pharm Sin B 14 (2024) 3493-3512]

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.018

Longhao Cheng , Xiaoxue Wang , Aijun Liu , Ying Zhu , Hu Cheng , Jiangling Yu , Lili Gong , Honglin Liu , Guolin Shen , Lihong Liu

引用次数: 0

The role of the microbiota–gut–brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism 微生物群-肠-脑轴在甲基苯丙胺诱导的神经毒性中的作用：微生物组成和短链脂肪酸代谢紊乱

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-11-01 DOI: 10.1016/j.apsb.2024.08.012

Lijian Chen , Kaikai Zhang , Jiali Liu , Xiuwen Li , Yi Liu , Hongsheng Ma , Jianzheng Yang , Jiahao Li , Long Chen , Clare Hsu , Jiahao Zeng , Xiaoli Xie , Qi Wang

{"title":"The role of the microbiota–gut–brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism","authors":"Lijian Chen , Kaikai Zhang , Jiali Liu , Xiuwen Li , Yi Liu , Hongsheng Ma , Jianzheng Yang , Jiahao Li , Long Chen , Clare Hsu , Jiahao Zeng , Xiaoli Xie , Qi Wang","doi":"10.1016/j.apsb.2024.08.012","DOIUrl":"10.1016/j.apsb.2024.08.012","url":null,"abstract":"<div><div>Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut–brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 11","pages":"Pages 4832-4857"},"PeriodicalIF":14.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186911","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 : 2024-11-01 DOI: 10.1016/S2211-3835(24)00392-7

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

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