Acta Pharmaceutica Sinica. B最新文献_第2页

A microfluidic coculture model for mapping signaling perturbations and precise drug screening against macrophage-mediated dynamic myocardial injury.

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1016/j.apsb.2024.11.004

Zhao Gao, Zhiyong Du, Yu Hou, Kun Hua, Pengfei Tu, Xiaoni Ai, Yong Jiang

{"title":"A microfluidic coculture model for mapping signaling perturbations and precise drug screening against macrophage-mediated dynamic myocardial injury.","authors":"Zhao Gao, Zhiyong Du, Yu Hou, Kun Hua, Pengfei Tu, Xiaoni Ai, Yong Jiang","doi":"10.1016/j.apsb.2024.11.004","DOIUrl":"10.1016/j.apsb.2024.11.004","url":null,"abstract":"<p><p>Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb<sub>1</sub> and protocatechualdehyde as promising cardioprotective candidates <i>in vitro</i> and <i>in vivo</i>. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.</p>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"5393-5406"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977078","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

Reductive stress-a common metabolic feature of obesity and cancer.

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI: 10.1016/j.apsb.2024.08.034

Man Luo, Xiwen Ma, Jianping Ye

{"title":"Reductive stress-a common metabolic feature of obesity and cancer.","authors":"Man Luo, Xiwen Ma, Jianping Ye","doi":"10.1016/j.apsb.2024.08.034","DOIUrl":"10.1016/j.apsb.2024.08.034","url":null,"abstract":"<p><p>Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD<sup>+</sup> ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepared to address the issue with new insights published recently. NADH is used in production of NADPH, glutathione, ATP and heat in the classical biochemistry. In obesity, elevation of NADH/NAD<sup>+</sup> ratio, likely from overproduction due to substrate overloading, has been found in the liver for insulin resistance and gluconeogenesis. New evidence demonstrates that the elevation may induce lipogenesis, purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and NRF2. In cancer cells, NADH/NAD<sup>+</sup> elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial respiration. Alternatively, NRF2 overactivation from gene mutation represents another mechanism of NADH/NAD<sup>+</sup> elevation from NADH production in the cancer cells. The elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential molecules. It appears that the causes of reductive stress are different between obesity and cancer, while its impact in anabolism is similar in the two conditions.</p>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"5181-5185"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977124","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

Intestinal epithelial cell NCoR deficiency ameliorates obesity and metabolic syndrome.

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 Epub Date: 2024-10-10 DOI: 10.1016/j.apsb.2024.09.019

Shaocong Hou, Hengcai Yu, Caihong Liu, Andrew M F Johnson, Xingfeng Liu, Qian Jiang, Qijin Zhao, Lijuan Kong, Yanjun Wan, Xiaowei Xing, Yibing Chen, Jingwen Chen, Qing Wu, Peng Zhang, Changtao Jiang, Bing Cui, Pingping Li

{"title":"Intestinal epithelial cell NCoR deficiency ameliorates obesity and metabolic syndrome.","authors":"Shaocong Hou, Hengcai Yu, Caihong Liu, Andrew M F Johnson, Xingfeng Liu, Qian Jiang, Qijin Zhao, Lijuan Kong, Yanjun Wan, Xiaowei Xing, Yibing Chen, Jingwen Chen, Qing Wu, Peng Zhang, Changtao Jiang, Bing Cui, Pingping Li","doi":"10.1016/j.apsb.2024.09.019","DOIUrl":"10.1016/j.apsb.2024.09.019","url":null,"abstract":"<p><p>Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPAR<i>α</i> and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPAR<i>α</i> activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPAR<i>α</i> activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.</p>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"5267-5285"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977116","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

Aclysiran, an RNAi therapeutic agent targeting ACLY, treats hypercholesterolemia and atherosclerosis in ApoE ^-/- mice.

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 Epub Date: 2024-10-24 DOI: 10.1016/j.apsb.2024.10.008

Meijie Chen, Peter J Little, Sudong Kong, Maciej Banach, Jianping Weng, Suowen Xu

引用次数: 0

Respiratory delivered vaccines: Current status and perspectives in rational formulation design.

IF 14.7 1区医学

Acta Pharmaceutica Sinica. B Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1016/j.apsb.2024.08.026

Lan Wu, Wenwen Xu, Huiyang Jiang, Mingshi Yang, Dongmei Cun

{"title":"Respiratory delivered vaccines: Current status and perspectives in rational formulation design.","authors":"Lan Wu, Wenwen Xu, Huiyang Jiang, Mingshi Yang, Dongmei Cun","doi":"10.1016/j.apsb.2024.08.026","DOIUrl":"10.1016/j.apsb.2024.08.026","url":null,"abstract":"<p><p>The respiratory tract is susceptible to various infections and can be affected by many serious diseases. Vaccination is one of the most promising ways that prevent infectious diseases and treatment of some diseases such as malignancy. Direct delivery of vaccines to the respiratory tract could mimic the natural process of infection and shorten the delivery path, therefore unique mucosal immunity at the first line might be induced and the efficiency of delivery can be high. Despite considerable attempts at the development of respiratory vaccines, the rational formulation design still warrants attention, <i>i.e.</i>, how the formulation composition, particle properties, formulation type (liquid or solid), and devices would influence the immune outcome. This article reviews the recent advances in the formulation design and development of respiratory vaccines. The focus is on the state of the art of delivering antigenic compounds through the respiratory tract, overcoming the pulmonary bio-barriers, enhancing delivery efficiencies of respiratory vaccines as well as maintaining the stability of vaccines during storage and use. The choice of devices and the influence of deposition sites on vaccine efficiencies were also reviewed.</p>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"14 12","pages":"5132-5160"},"PeriodicalIF":14.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977127","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