Biomedicine & Pharmacotherapy最新文献

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An insight into allele-selective approaches to lowering mutant huntingtin protein for Huntington’s disease treatment 洞察等位基因选择性降低突变亨廷顿蛋白以治疗亨廷顿氏症的方法
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117557
Jia-yuan Yao , Ting Liu , Xin-ru Hu , Hui Sheng , Zi-hao Chen , Hai-yang Zhao , Xiao-jia Li , Yang Wang , Liang Hao
{"title":"An insight into allele-selective approaches to lowering mutant huntingtin protein for Huntington’s disease treatment","authors":"Jia-yuan Yao ,&nbsp;Ting Liu ,&nbsp;Xin-ru Hu ,&nbsp;Hui Sheng ,&nbsp;Zi-hao Chen ,&nbsp;Hai-yang Zhao ,&nbsp;Xiao-jia Li ,&nbsp;Yang Wang ,&nbsp;Liang Hao","doi":"10.1016/j.biopha.2024.117557","DOIUrl":"10.1016/j.biopha.2024.117557","url":null,"abstract":"<div><div>Huntington's disease (HD), a monogenic neurodegenerative disorder, stems from a CAG repeat expansion within the mutant huntingtin gene (<em>HTT</em>). This leads to a detrimental gain-of-function of the mutated huntingtin protein (mHTT). As of now, there exist no efficacious therapies to alter the disease progression. In view of the monogenetic mutation nature and an indispensable role of wild-type <em>HTT</em> in healthy neurodevelopment and cellular functions, the developing strategy of allele-selectively deleting/silencing mutant <em>HTT</em> as well as only inactivating mHTT without altering wild-type <em>HTT</em> or wild-type huntingtin protein (wtHTT) comes highly recommended, and may offer a promising treatment option for HD. Here, we reviewed the therapeutic approaches that allele-selective lowering mHTT expression by targeting only mutant <em>HTT</em> DNA, RNA and mHTT along with recent preclinical and clinical outcomes and challenges, in anticipation of some novel ideas to be introduced into HD therapeutic research.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Dissecting the roles of prosaposin as an emerging therapeutic target for tumors and its underlying mechanisms 剖析作为肿瘤新兴治疗靶点的丙种球蛋白的作用及其内在机制
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117551
Lirong Yan , Zhenpeng Wen , Yi Yang , Aoran Liu , Fang Li , Yuzhe Zhang , Chunjiao Yang , Yanke Li , Ye Zhang
{"title":"Dissecting the roles of prosaposin as an emerging therapeutic target for tumors and its underlying mechanisms","authors":"Lirong Yan ,&nbsp;Zhenpeng Wen ,&nbsp;Yi Yang ,&nbsp;Aoran Liu ,&nbsp;Fang Li ,&nbsp;Yuzhe Zhang ,&nbsp;Chunjiao Yang ,&nbsp;Yanke Li ,&nbsp;Ye Zhang","doi":"10.1016/j.biopha.2024.117551","DOIUrl":"10.1016/j.biopha.2024.117551","url":null,"abstract":"<div><div>As a dual-function protein, prosaposin (PSAP) is a lysosome-associated protein that participates in a variety of cellular processes. In the lysosome, PSAP is processed to activate enzymes that degrade lipids. In addition, PSAP proteins located extracellularly are involved in cancer progression, such as proliferation and tumor death suppression signaling. Moreover, under different situations, PSAP exhibits distinct metastasis potentials in tumors. However, comprehensive insight into PSAP in cancer progression has been lacking. Here, we provide a framework of the role of PSAP in cancer and its clinical application in cancer patients, providing a novel perspective on the clinical translation of PSAP.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Oleanolic acid 28-O-β-D-glucopyranoside: A novel therapeutic agent against ulcerative colitis via anti-inflammatory, barrier-preservation, and gut microbiota-modulation 齐墩果酸 28-O-β-D-吡喃葡萄糖苷:通过抗炎、屏障保护和肠道微生物群调节治疗溃疡性结肠炎的新型治疗剂
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117534
Caixia Wang , Hanlin Liu , Zhuoqiao Li , Qingya Yang , Qianyun Wang , Ting Yang , Daohao Tang , Cuizhu Wang , Jinping Liu
{"title":"Oleanolic acid 28-O-β-D-glucopyranoside: A novel therapeutic agent against ulcerative colitis via anti-inflammatory, barrier-preservation, and gut microbiota-modulation","authors":"Caixia Wang ,&nbsp;Hanlin Liu ,&nbsp;Zhuoqiao Li ,&nbsp;Qingya Yang ,&nbsp;Qianyun Wang ,&nbsp;Ting Yang ,&nbsp;Daohao Tang ,&nbsp;Cuizhu Wang ,&nbsp;Jinping Liu","doi":"10.1016/j.biopha.2024.117534","DOIUrl":"10.1016/j.biopha.2024.117534","url":null,"abstract":"<div><div>Ulcerative colitis (UC), an incurable and recurrent inflammatory bowel disease, presents a significant threat to health and highlights the need for novel therapeutic strategies. Oleanolic acid 28-<em>O-β</em>-D-glucopyranoside (OAG) is a naturally occurring pentacyclic triterpenoid found in ginseng. In this study, we demonstrated that OAG exhibited remarkable anti-UC activity in LPS-induced Caco-2 cells and DSS-induced model mice. First, OAG alleviated the symptoms of UC by mitigating weight loss, reducing the DAI score, and increasing colon length. Second, the inflammatory response was inhibited after OAG intervention, evidenced decreases in the spleen coefficient, cytokine levels, and inflammatory cell infiltration in colon tissue. Thirdly, OAG also enhanced intestinal epithelial barrier function, as evidenced by elevated TEER values, increased expression of tight junction proteins, diminished bacterial translocation, and maintained intact ultrastructure of colonic mucosal cells. Notably, compared with 5-aminosalicylic acid, OAG demonstrated superior efficacy in enhancing mucosal barrier function. Fourth, OAG increased microbial diversity, promoted the abundance of beneficial bacteria, reduced the abundance of harmful bacteria, and rebalanced the gut microbiome. Finally, the PI3K-AKT and MAPK signaling pathways were identified as crucial mechanisms underlying the therapeutic effects of OAG against UC through multi-omics. In summary, we identified OAG as a novel therapeutic agent against UC, demonstrating anti-inflammatory, barrier-preserving, and gut microbiota-modulating effects, highlighting its promising potential as a candidate UC drug.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses 皮内注射新型沙眼衣原体微粒候选疫苗可产生保护性免疫反应
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117563
Dung T. Huynh , Emanuele Nolfi , Safia Guleed , Lobna Medfai , Natascha Wolf , Rienke F. Uijen , Marien I. de Jonge , Peter van Ulsen , Jes Dietrich , Joen Luirink , Alice J.A.M. Sijts , Wouter S.P. Jong
{"title":"Intradermal administration of novel particulate Chlamydia trachomatis vaccine candidates drives protective immune responses","authors":"Dung T. Huynh ,&nbsp;Emanuele Nolfi ,&nbsp;Safia Guleed ,&nbsp;Lobna Medfai ,&nbsp;Natascha Wolf ,&nbsp;Rienke F. Uijen ,&nbsp;Marien I. de Jonge ,&nbsp;Peter van Ulsen ,&nbsp;Jes Dietrich ,&nbsp;Joen Luirink ,&nbsp;Alice J.A.M. Sijts ,&nbsp;Wouter S.P. Jong","doi":"10.1016/j.biopha.2024.117563","DOIUrl":"10.1016/j.biopha.2024.117563","url":null,"abstract":"<div><div><em>Chlamydia trachomatis</em> causes the most prevalent bacterial sexually transmitted infection worldwide. Its complex lifecycle and the lack of appropriate antigen delivery vehicles make it difficult to develop an effective <em>C. trachomatis</em> vaccine. Recently, bacterial protein bodies (PBs) have emerged as promising bioparticles for vaccine antigen delivery. By developing a PB-tag for translational fusion, we were able to induce the aggregation of recombinant antigens expressed in <em>Escherichia coli</em> into PBs. Here, we investigated the immunogenicity and efficacy of PBs containing either the <em>C. trachomatis</em> MOMP-derived CTH522-SP or HtrA antigen in mice. Intradermal administration of c-di-AMP-adjuvanted PB-CTH522-SP and PB-HtrA vaccines, produced in an LPS-detoxified <em>E. coli</em> strain, induced antigen-specific cellular immunity, as measured by significant release of IFN-γ and IL17a in draining cervical lymph node and splenic cell cultures. Moreover, significant induction of HtrA-specific IFN-γ expressing CD4<sup>+</sup> and CD8<sup>+</sup> T cells was detected in the spleens. While immunization with the two PB vaccines led to prominent levels of specific antibodies in both serum and vaginal compartments, only antiserum against PB-CTH522-SP exhibited <em>C. trachomatis</em>-specific neutralization activity. Importantly, intradermal immunization with PB-CTH522-SP significantly reduced bacterial counts following <em>C. trachomatis</em> genital challenge. These data highlight the potential of the PB-based platform for the development of <em>C. trachomatis</em> vaccines.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 in nano-immunotherapy for gynecological cancers: A new frontier 妇科癌症纳米免疫疗法的进展:新领域
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117553
Xiao Gu , Cuicui Wang
{"title":"Advancements in nano-immunotherapy for gynecological cancers: A new frontier","authors":"Xiao Gu ,&nbsp;Cuicui Wang","doi":"10.1016/j.biopha.2024.117553","DOIUrl":"10.1016/j.biopha.2024.117553","url":null,"abstract":"<div><div>Gynecological cancers rank among the leading causes of death for women worldwide. Traditional treatment methods, including surgery, chemotherapy, and radiotherapy, are commonly employed in patients with these tumors. However, the effectiveness of these approaches remains suboptimal due to issues like treatment resistance and challenges in early detection. As an alternative, immunotherapy has shown promise by offering improved anti-tumor responses and fewer side effects. In recent years, there have been significant advances in nanoparticle (NP) and nanoengineering technologies, paving the way for the development of nano-immunotherapy—an approach designed to enhance the effectiveness of immunotherapy. Thanks to the flexibility, adaptability, small size, and responsiveness of NP platforms to the tumor microenvironment (TME), nano-immunotherapy has demonstrated improved anti-tumor activity and safety. This is achieved through enhanced tumor targeting, better delivery of immune agents, and reduced toxicity and side effects. Recently, researchers have explored the application of nano-immunotherapy in treating gynecological cancers, aiming to slow tumor progression and improve patient outcomes. In this review, we provide an overview of the latest advances in nano-immunotherapy for gynecological cancers, including ovarian, cervical, and endometrial cancers. Additionally, we discuss the challenges facing the clinical translation of nano-immunotherapy from the lab to real-world applications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Advances in nanoparticle-based therapeutics for ischemic stroke: Enhancing drug delivery and efficacy 基于纳米粒子的缺血性中风疗法的进展:增强药物输送和疗效
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117564
Peng Ji , Qingqing Xu , Jiahui Li , Zihan Wang , Wanyi Mao , Peng Yan
{"title":"Advances in nanoparticle-based therapeutics for ischemic stroke: Enhancing drug delivery and efficacy","authors":"Peng Ji ,&nbsp;Qingqing Xu ,&nbsp;Jiahui Li ,&nbsp;Zihan Wang ,&nbsp;Wanyi Mao ,&nbsp;Peng Yan","doi":"10.1016/j.biopha.2024.117564","DOIUrl":"10.1016/j.biopha.2024.117564","url":null,"abstract":"<div><div>Ischemic stroke, characterized by vascular occlusion, has recently emerged as one of the primary causes of mortality and disability worldwide. Conventional treatment modalities, such as thrombolytic and neuroprotective therapies, face numerous challenges, including limited bioavailability, significant neurotoxicity, suboptimal targeting, short half-life, and poor blood-brain barrier (BBB) penetration. Nanoparticle-based drug delivery systems present distinct advantages, such as small size, enhanced lipophilicity, and modifiability, which can potentially address these limitations. Utilizing nanoparticles for drug delivery in ischemic stroke therapy offers improved drug bioavailability, reduced neurotoxicity, enhanced targeted delivery, prolonged drug half-life, and better dissolution kinetics. This review aims to provide a comprehensive overview of current strategies in preclinical studies for managing or preventing ischemic stroke from a nanomaterial perspective, highlighting the advantages and limitations of each approach.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
N-butanol extract of Broussonetia papyrifera (L.) L′Hér. ex Vent root bark alleviates atopic dermatitis by targeting E3 ubiquitin ligase WWP1 to promote NLRP3 degradation Broussonetia papyrifera (L.) L′Hér. ex Vent根皮正丁醇提取物通过靶向E3泛素连接酶WWP1促进NLRP3降解缓解特应性皮炎
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-13 DOI: 10.1016/j.biopha.2024.117561
Cheng Zeng , Liangkun Weng , Yuanming Song , Yihang Huang , Wenjing Xiang , Zhiming Ye , Can Yu , Zixuan Lai , Yuxuan Song , Huiwen Yang , Luyong Zhang , Bing Liu
{"title":"N-butanol extract of Broussonetia papyrifera (L.) L′Hér. ex Vent root bark alleviates atopic dermatitis by targeting E3 ubiquitin ligase WWP1 to promote NLRP3 degradation","authors":"Cheng Zeng ,&nbsp;Liangkun Weng ,&nbsp;Yuanming Song ,&nbsp;Yihang Huang ,&nbsp;Wenjing Xiang ,&nbsp;Zhiming Ye ,&nbsp;Can Yu ,&nbsp;Zixuan Lai ,&nbsp;Yuxuan Song ,&nbsp;Huiwen Yang ,&nbsp;Luyong Zhang ,&nbsp;Bing Liu","doi":"10.1016/j.biopha.2024.117561","DOIUrl":"10.1016/j.biopha.2024.117561","url":null,"abstract":"<div><h3>Background</h3><div><em>Broussonetia papyrifera</em> (L.) L′Hér. ex Vent (<em>B. papyrifera</em>) is a deciduous tree widely distributed in Asia. Previous studies have revealed that leaves of <em>B. papyrifera</em> ameliorated atopic dermatitis (AD)-like symptoms and inflammatory response. However, the impact and underlying mechanism of other parts of <em>B. papyrifera</em> on AD remain elusive<em>.</em></div></div><div><h3>Methods</h3><div>The AD mice induced by 1-Chloro-2,4-dinitrochlorobenzene were used to observe the histopathological alterations in the skin tissues using hematoxylin-eosin staining and toluidine blue staining techniques. Serum levels of inflammatory factors were quantified utilizing ELISA. Pyroptosis was analyzed by lactate dehydrogenase release and flow cytometry in human keratinocytes. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome was analyzed by western blots. Furthermore, the mechanism underlying the inhibition of NLRP3 inflammasome by N-butanol extracts of B. papyrifera root bark (NE-BPRB) was investigated using cellular thermal shift assay and surface plasmon resonance techniques.</div></div><div><h3>Results</h3><div>Treatment with NE-BPRB significantly ameliorated symptoms of AD mice and reduced serum levels of pro-inflammatory factors. NE-BPRB intervention exhibited inhibitory effects on NLRP3 inflammasome activation and pyroptosis <em>in vitro</em> and <em>in vivo</em>. NE-BPRB and its primary bioactive constituent chlorogenic acid (CA) promote the K48-linked ubiquitination of NLRP3, leading to its proteasomal degradation by binding WW domain containing E3 ubiquitin protein ligase 1 (WWP1).</div></div><div><h3>Conclusions</h3><div>The NE-BPRB and its primary bioactive constituent, CA, effectively inhibit the formation of the NLRP3 inflammasome and impede cell pyroptosis by promoting K48-linked ubiquitin-dependent proteasomal degradation of NLRP3 through binding to the E3 ubiquitin ligase WWP1, thereby resulting in improved AD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 in nano drug delivery system for liver cancer therapy based on mitochondria-targeting 基于线粒体靶向的肝癌治疗纳米给药系统的研究进展
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-11 DOI: 10.1016/j.biopha.2024.117520
Lixia Chen , Yitian He , Jinshuai Lan , Zhe Li , Donghao Gu , Wenlong Nie , Tong Zhang , Yue Ding
{"title":"Advancements in nano drug delivery system for liver cancer therapy based on mitochondria-targeting","authors":"Lixia Chen ,&nbsp;Yitian He ,&nbsp;Jinshuai Lan ,&nbsp;Zhe Li ,&nbsp;Donghao Gu ,&nbsp;Wenlong Nie ,&nbsp;Tong Zhang ,&nbsp;Yue Ding","doi":"10.1016/j.biopha.2024.117520","DOIUrl":"10.1016/j.biopha.2024.117520","url":null,"abstract":"<div><div>Based on poor efficacy and non-specific toxic side effects of conventional drug therapy for liver cancer, nano-based drug delivery system (NDDS) offers the advantage of drug targeting delivery. Subcellular targeting of nanomedicines on this basis enables more precise and effective termination of tumor cells. Mitochondria, as the crucial cell powerhouse, possesses distinctive physical and chemical properties in hepatoma cells different from that in hepatic cells, and controls apoptosis, tumor metastasis, and cellular drug resistance in hepatoma cells through metabolism and dynamics, which serves as a good choice for drug targeting delivery. Thus, mitochondria-targeting NDDS have become a recent research focus, showcasing the design of cationic nanoparticles, metal nanoparticles, mitochondrial peptide modification and so on. Although many studies have shown good results regarding anti-tumor efficacy, it is a long way to go before the successful translation of clinical application. Based on these, we summarized the specificity and importance of mitochondria in hepatoma cells, and reviewed the current mitochondria-targeting NDDS for liver cancer therapy, aiming to provide a better understanding for current development process, strengths and weaknesses of mitochondria-targeting NDDS as well as informing subsequent improvements and developments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117520"},"PeriodicalIF":6.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Scoulerine: A natural isoquinoline alkaloid targeting SLC6A3 to treat RCC Scoulerine:一种靶向 SLC6A3 的天然异喹啉生物碱,用于治疗 RCC
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-11 DOI: 10.1016/j.biopha.2024.117524
Tianrui Qu , Yu Sun , Jingying Zhao , Nanqi Liu , Jianli Yang , Dantong Lyu , Wenjie Huang , Weizhen Zhan , Tao Li , Zichuan Yao , Rongbo Yan , Haiyan Zhang , Hong Hong , Liye Shi , Xin Meng , Bo Yin
{"title":"Scoulerine: A natural isoquinoline alkaloid targeting SLC6A3 to treat RCC","authors":"Tianrui Qu ,&nbsp;Yu Sun ,&nbsp;Jingying Zhao ,&nbsp;Nanqi Liu ,&nbsp;Jianli Yang ,&nbsp;Dantong Lyu ,&nbsp;Wenjie Huang ,&nbsp;Weizhen Zhan ,&nbsp;Tao Li ,&nbsp;Zichuan Yao ,&nbsp;Rongbo Yan ,&nbsp;Haiyan Zhang ,&nbsp;Hong Hong ,&nbsp;Liye Shi ,&nbsp;Xin Meng ,&nbsp;Bo Yin","doi":"10.1016/j.biopha.2024.117524","DOIUrl":"10.1016/j.biopha.2024.117524","url":null,"abstract":"<div><div>Scoulerine, an isoquinoline alkaloid derived from the corydalis plant, exhibits diverse therapeutic properties against tumors, Alzheimer's disease, and inflammation. This research delves into the pharmacological impact and underlying mechanism of scoulerine on renal cell carcinoma (RCC). Our findings suggest that Scoulerine displays promise as a potential therapeutic agent for RCC, demonstrating notable inhibitory effects in both in vivo and in vitro models. In addition, scoulerine inhibited the viability of 769-P and 786-O cell lines in a time-dependent and dose-dependent manner, and promoted the level of apoptosis associated with B-cell lymphoma-2 associated X protein (Bax). Moreover, the administration of scoulerine resulted in a significant suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Subsequently, utilizing bioinformatics and spatial transcriptomic databases, we identified solute carrier family 6 Member 3 (SLC6A3) as the most promising target of scoulerine. Through experimental validation, we confirmed the functional and therapeutic relevance of SLC6A3 in scoulerine-mediated treatment of RCC. The results of our study indicate a significant affinity between scoulerine and SLC6A3, with competitive inhibition of this interaction leading to a reduction in the inhibitory impact of scoulerine on RCC cell viability. In conclusion, our findings suggest that scoulerine may induce apoptosis in RCC by targeting SLC6A3 and inhibiting the activation of the MAPK signaling pathway, thereby positioning it as a promising natural compound for potential future RCC treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117524"},"PeriodicalIF":6.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Carnosic acid ameliorates postinflammatory hyperpigmentation by inhibiting inflammatory reaction and melanin deposition 肉苁蓉酸能抑制炎症反应和黑色素沉积,从而改善炎症后色素沉着。
IF 6.9 2区 医学
Biomedicine & Pharmacotherapy Pub Date : 2024-10-10 DOI: 10.1016/j.biopha.2024.117522
Heyi Su , Fan Yang , Keyi Lu , Jiaxian Ma , Guangming Huo , Shengjie Li , Jianmei Li
{"title":"Carnosic acid ameliorates postinflammatory hyperpigmentation by inhibiting inflammatory reaction and melanin deposition","authors":"Heyi Su ,&nbsp;Fan Yang ,&nbsp;Keyi Lu ,&nbsp;Jiaxian Ma ,&nbsp;Guangming Huo ,&nbsp;Shengjie Li ,&nbsp;Jianmei Li","doi":"10.1016/j.biopha.2024.117522","DOIUrl":"10.1016/j.biopha.2024.117522","url":null,"abstract":"<div><div>The potential therapeutic effects of carnosic acid (CA) on postinflammatory hyperpigmentation (PIH) were evaluated, including its effects on melanin deposition in zebrafish, melanogenesis and melanosome transfer in skin cells and skin wound healing in mice. Our results demonstrated that CA dose-dependently decreased melanin deposition in the skin of juvenile zebrafishes. It also inhibited melanogenesis in melanoma cells and melanosome transfer to keratinocytes. Next, CA was loaded in a liposome-hydrogel system (LP-GEL) to treat skin wounds in mice. The results showed that CA-LP-GEL, as well as LP-GEL, could accelerate skin wound healing and repair the structure of healing skins in mice. Comparatively, the levels of inflammatory factors (IL-1β and TNF-a) in healing skins were significantly increased by LP-GEL, but reduced by CA-LP-GEL. In addition, Fontana-Masson staining analysis of healing skin showed that the melanoma cells were restored by the treatment of LP-GEL and CA-LP-GEL, while the melanin content was significantly increased only by LP-GEL. Real-time PCR data showed that CA decreased the gene expression related with melanogenesis (MITF, TYR and TRP-1), melanosome transfer (MLPH, Myova and Rab27a) and inflammatory cytokines (IL-1β and TNF-α) <em>in vitro</em> and <em>in vivo</em>. In conclusion, CA could reduce melanin deposition in the skin by inhibiting melanogenesis and melanosome transfer. CA-LP-GEL was found to accelerate skin wound healing and suppress inflammation and hyperpigmentation in mice. These results suggest that CA has a big developing potentiality for PIH treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"180 ","pages":"Article 117522"},"PeriodicalIF":6.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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