Acta Pharmaceutica Sinica. B最新文献

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

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}

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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