Pub Date : 2024-08-14DOI: 10.1016/j.phrs.2024.107349
In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.
在未来的再生医学中,远红外线(FIR)可能是光学疗法的重要组成部分。许多研究已经证实或验证了远红外线对各种疾病的疗效和安全性,这得益于对远红外线机理的新认识和许多应用的卓越性能。然而,由于对红外热像仪的生物效应和治疗参数缺乏共识,限制了其在临床上的实际应用。在这篇综述中,我们系统地阐述了 FIR 的定义、特点和基本原理。我们概述了 FIR 的治疗参数,包括波长范围、功率密度、照射时间和距离。此外,还讨论了 FIR 的生物效应、潜在分子机制以及临床前和临床应用。此外,本综述还介绍了红外热辐射的未来发展和应用。通过应用最佳治疗参数,红外热像仪可以影响各种细胞、动物模型和患者,激发不同的潜在机制,为许多疾病提供治疗潜力。在未来的再生医学中,红外热像仪可能是一种具有广阔应用前景的优质替代疗法。
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Pub Date : 2024-08-13DOI: 10.1016/j.phrs.2024.107335
Background
Faricimab stands as the inaugural and sole bispecific antibody approved by the US Food and Drug Administration (FDA) for intravitreal injection. Nonetheless, the efficacy and safety of intravitreal faricimab remained uncertain.
Objectives
The purpose of this study was to evaluate faricimab.
Methods
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42023398320). Five databases (Pubmed, Embase, Web of science, Cochrane Library, ClinicalTrials gov) were searched. We calculated pooled standard mean difference or odds ratio with 95 % confident interval under a random-effect model or fixed-effect model. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was employed to ascertain the reliability of the analyses. Trial sequential analysis was performed to gauge the statistical reliability of the data in the cumulative meta-analysis.
Results
8 studies (3975 participants) were included. The use of faricimab was associated with central subfield thickness (CST) change, but no difference was found in other primary efficacy outcomes. Apart from that, a correlation was observed between the use of faricimab and the risk of vitreous floaters. Based on TSA, strong evidence indicates that compared to the control group, faricimab aided in reducing CST but increasing the risk of vitreous floaters.
Conclusions
In this study, a correlation existed between the use of faricimab and a reduction in CST, indicating a superior therapeutic effect. Moreover, participants treated with faricimab demonstrated a higher risk of vitreous floaters. More randomized controlled trials are essential to further explore the efficacy and safety of faricimab.
背景:法利单抗是美国食品和药物管理局(FDA)批准用于玻璃体内注射的首个也是唯一一个双特异性抗体。然而,玻璃体内注射法利西单抗的疗效和安全性仍不确定:本研究旨在评估法尼单抗:本系统综述和荟萃分析遵循了系统综述和荟萃分析首选报告项目(Preferred Reporting Items for Systematic Reviews and Meta-Analyses,PRISMA)指南(CRD42023398320)。我们检索了五个数据库(Pubmed、Embase、Web of science、Cochrane Library、ClinicalTrials gov)。在随机效应模型或固定效应模型下,我们计算了汇集的标准平均差或几率比率及 95% 的置信区间。我们采用了推荐、评估、发展和评价分级法(GRADE)来确定分析的可靠性。进行了试验序列分析,以衡量累积荟萃分析中数据的统计可靠性:共纳入 8 项研究(3975 名参与者)。使用法尼单抗与中心视野下厚度(CST)的变化有关,但在其他主要疗效结果中未发现差异。除此之外,还观察到使用法尼单抗与玻璃体漂浮物风险之间存在相关性。基于TSA,有力的证据表明,与对照组相比,法尼单抗有助于降低CST,但会增加玻璃体漂浮物的风险:在这项研究中,法尼单抗的使用与 CST 的减少之间存在相关性,这表明法尼单抗具有卓越的治疗效果。此外,接受法尼单抗治疗的患者出现玻璃体漂浮物的风险较高。要进一步探讨法尼单抗的疗效和安全性,必须进行更多的随机对照试验。
{"title":"Comprehensive assessment of the impact of intravitreal faricimab on retinal diseases: A systematic review, meta-analysis, and trial sequential analysis","authors":"","doi":"10.1016/j.phrs.2024.107335","DOIUrl":"10.1016/j.phrs.2024.107335","url":null,"abstract":"<div><h3>Background</h3><p>Faricimab stands as the inaugural and sole bispecific antibody approved by the US Food and Drug Administration (FDA) for intravitreal injection. Nonetheless, the efficacy and safety of intravitreal faricimab remained uncertain.</p></div><div><h3>Objectives</h3><p>The purpose of this study was to evaluate faricimab.</p></div><div><h3>Methods</h3><p>This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42023398320). Five databases (Pubmed, Embase, Web of science, Cochrane Library, ClinicalTrials gov) were searched. We calculated pooled standard mean difference or odds ratio with 95 % confident interval under a random-effect model or fixed-effect model. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was employed to ascertain the reliability of the analyses. Trial sequential analysis was performed to gauge the statistical reliability of the data in the cumulative meta-analysis.</p></div><div><h3>Results</h3><p>8 studies (3975 participants) were included. The use of faricimab was associated with central subfield thickness (CST) change, but no difference was found in other primary efficacy outcomes. Apart from that, a correlation was observed between the use of faricimab and the risk of vitreous floaters. Based on TSA, strong evidence indicates that compared to the control group, faricimab aided in reducing CST but increasing the risk of vitreous floaters.</p></div><div><h3>Conclusions</h3><p>In this study, a correlation existed between the use of faricimab and a reduction in CST, indicating a superior therapeutic effect. Moreover, participants treated with faricimab demonstrated a higher risk of vitreous floaters. More randomized controlled trials are essential to further explore the efficacy and safety of faricimab.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002809/pdfft?md5=ecef5838b7c7545ad606b7f9196dc6d7&pid=1-s2.0-S1043661824002809-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988594","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}
Pub Date : 2024-08-13DOI: 10.1016/j.phrs.2024.107352
A cutting-edge approach in cell-based immunotherapy for combating resistant cancer involves genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes. In recent years, these therapies have demonstrated effectiveness, leading to their commercialization and clinical application against certain types of cancer. However, CAR-T therapy faces limitations, such as the immunosuppressive tumour microenvironment (TME) that can render CAR-T cells ineffective, and the adverse side effects of the therapy, including cytokine release syndrome (CRS). Extracellular vesicles (EVs) are a diverse group of membrane-bound particles released into the extracellular environment by virtually all cell types. They are essential for intercellular communication, transferring cargoes such as proteins, lipids, various types of RNAs, and DNA fragments to target cells, traversing biological barriers both locally and systemically. EVs play roles in numerous physiological processes, with those from both immune and non-immune cells capable of modulating the immune system through activation or suppression. Leveraging this capability of EVs to enhance CAR-T cell therapy could represent a significant advancement in overcoming its current limitations. This review examines the current landscape of CAR-T cell immunotherapy and explores the potential role of EVs in augmenting its therapeutic efficacy.
以细胞为基础的免疫疗法中用于抗击耐药性癌症的前沿方法涉及基因工程嵌合抗原受体 T(CAR-T)淋巴细胞。近年来,这些疗法已显示出疗效,并因此实现了商业化和临床应用,用于治疗某些类型的癌症。然而,CAR-T疗法也面临着一些限制,如免疫抑制性肿瘤微环境(TME)会使CAR-T细胞失效,以及疗法的不良副作用,包括细胞因子释放综合征(CRS)。细胞外囊泡(EVs)是由几乎所有类型的细胞释放到细胞外环境中的各种膜结合颗粒。它们对细胞间的交流至关重要,可将蛋白质、脂类、各种类型的 RNA 和 DNA 片段等货物转移到靶细胞,并穿越局部和全身的生物屏障。EVs在许多生理过程中发挥作用,来自免疫细胞和非免疫细胞的EVs都能通过激活或抑制作用调节免疫系统。利用EVs的这种能力来增强CAR-T细胞疗法,是克服其目前局限性的一大进步。本综述研究了 CAR-T 细胞免疫疗法的现状,并探讨了 EVs 在增强其疗效方面的潜在作用。
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Pub Date : 2024-08-12DOI: 10.1016/j.phrs.2024.107330
{"title":"Correspondence: Reply to commentary on “Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis”","authors":"","doi":"10.1016/j.phrs.2024.107330","DOIUrl":"10.1016/j.phrs.2024.107330","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002755/pdfft?md5=099f917f9c8065702e98001c35de313d&pid=1-s2.0-S1043661824002755-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982966","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}
Pub Date : 2024-08-12DOI: 10.1016/j.phrs.2024.107342
Recent advancements in immunology and islet biology have unveiled remarkable prospects for the postponement of Type 1 diabetes (T1D) through the strategic modulation of the immune system. In this Perspective, we discuss the pharmaceutical strides achieved, traversing from pre-clinical validation to the execution of impactful clinical trials. We begin with the initial investigations involving cyclosporine and glucocorticoids in rodent models, such as the non-obese diabetic (NOD) mouse, which guided early clinical trials. We then discuss the pre-clinical studies using suitable mouse models that eventually led to contemporary clinical trials targeting immune cell functionality and cytokine signaling pathways. Collectively, these discoveries promote the exciting paradigm of immune system modulation to mitigate autoimmunity, which continues to broaden. Notably, the use of baricitinib, a potent JAK1/2 inhibitor, and teplizumab, an anti-CD3 monoclonal antibody, represent discrete methodologies converging upon a singular outcome: the preservation of islet beta-cell functionality. The latter interventional strategies build on the original idea that tempering specific facets of the immune system will generate therapeutic benefit. Enthusiasm from these discoveries stems from efficacy with reduced side effects when compared with past approaches. The success of therapeutic intervention(s) in pre-clinical studies, combined with knowledge about stages of progression to clinical T1D, have ultimately encouraged the design of more successful clinical trials targeting highly specific populations at risk. Collectively, these findings instill a profound sense of optimism, suggesting that the prevention and even reversal of T1D may soon be within reach.
{"title":"From pre-clinical efficacy to promising clinical trials that delay Type 1 diabetes","authors":"","doi":"10.1016/j.phrs.2024.107342","DOIUrl":"10.1016/j.phrs.2024.107342","url":null,"abstract":"<div><p>Recent advancements in immunology and islet biology have unveiled remarkable prospects for the postponement of Type 1 diabetes (T1D) through the strategic modulation of the immune system. In this Perspective, we discuss the pharmaceutical strides achieved, traversing from pre-clinical validation to the execution of impactful clinical trials. We begin with the initial investigations involving cyclosporine and glucocorticoids in rodent models, such as the non-obese diabetic (NOD) mouse, which guided early clinical trials. We then discuss the pre-clinical studies using suitable mouse models that eventually led to contemporary clinical trials targeting immune cell functionality and cytokine signaling pathways. Collectively, these discoveries promote the exciting paradigm of immune system modulation to mitigate autoimmunity, which continues to broaden. Notably, the use of baricitinib, a potent JAK1/2 inhibitor, and teplizumab, an anti-CD3 monoclonal antibody, represent discrete methodologies converging upon a singular outcome: the preservation of islet beta-cell functionality. The latter interventional strategies build on the original idea that tempering specific facets of the immune system will generate therapeutic benefit. Enthusiasm from these discoveries stems from efficacy with reduced side effects when compared with past approaches. The success of therapeutic intervention(s) in pre-clinical studies, combined with knowledge about stages of progression to clinical T1D, have ultimately encouraged the design of more successful clinical trials targeting highly specific populations at risk. Collectively, these findings instill a profound sense of optimism, suggesting that the prevention and even reversal of T1D may soon be within reach.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002871/pdfft?md5=ebcdc7beea1074a6acdd55c8715a3eb5&pid=1-s2.0-S1043661824002871-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982967","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}
Pub Date : 2024-08-10DOI: 10.1016/j.phrs.2024.107345
Inflammation is the response of the human body to injury, infection, or other abnormal states, which is involved in the development of many diseases. As a member of the Krüppel-like transcription factors (KLFs) family, KLF4 plays a crucial regulatory role in physiological and pathological processes due to its unique dual domain of transcriptional activation and inhibition. A growing body of evidence has demonstrated that KLF4 plays a pivotal role in the pathogenesis of various inflammatory disorders, including inflammatory bowel disease, osteoarthritis, renal inflammation, pneumonia, neuroinflammation, and so on. Consequently, KLF4 has emerged as a promising new therapeutic target for inflammatory diseases. This review systematically generalizes the molecular regulatory network, specific functions, and mechanisms of KLF4 to elucidate its complex roles in inflammatory diseases. An in-depth study on the biological function of KLF4 is anticipated to offer a novel research perspective and potential intervention strategies for inflammatory diseases.
{"title":"A review of KLF4 and inflammatory disease: Current status and future perspective","authors":"","doi":"10.1016/j.phrs.2024.107345","DOIUrl":"10.1016/j.phrs.2024.107345","url":null,"abstract":"<div><p>Inflammation is the response of the human body to injury, infection, or other abnormal states, which is involved in the development of many diseases. As a member of the Krüppel-like transcription factors (KLFs) family, KLF4 plays a crucial regulatory role in physiological and pathological processes due to its unique dual domain of transcriptional activation and inhibition. A growing body of evidence has demonstrated that KLF4 plays a pivotal role in the pathogenesis of various inflammatory disorders, including inflammatory bowel disease, osteoarthritis, renal inflammation, pneumonia, neuroinflammation, and so on. Consequently, KLF4 has emerged as a promising new therapeutic target for inflammatory diseases. This review systematically generalizes the molecular regulatory network, specific functions, and mechanisms of KLF4 to elucidate its complex roles in inflammatory diseases. An in-depth study on the biological function of KLF4 is anticipated to offer a novel research perspective and potential intervention strategies for inflammatory diseases.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002901/pdfft?md5=306d7dd980c0021858fd5e543b99bc8d&pid=1-s2.0-S1043661824002901-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971620","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}
Pub Date : 2024-08-10DOI: 10.1016/j.phrs.2024.107341
Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.
{"title":"Natural-source payloads used in the conjugated drugs architecture for cancer therapy: Recent advances and future directions","authors":"","doi":"10.1016/j.phrs.2024.107341","DOIUrl":"10.1016/j.phrs.2024.107341","url":null,"abstract":"<div><p>Drug conjugates are obtained from tumor-located vectors connected to cytotoxic agents via linkers, which are designed to deliver hyper-toxic payloads directly to targeted cancer cells. These drug conjugates include antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), nucleic acid aptamer-drug conjugates (ApDCs), and virus-like drug conjugate (VDCs), which show great therapeutic value in the clinic. Drug conjugates consist of a targeting carrier, a linker, and a payload. Payloads are key therapy components. Cytotoxic molecules and their derivatives derived from natural products are commonly used in the payload portion of conjugates. The ideal payload should have sufficient toxicity, stability, coupling sites, and the ability to be released under specific conditions to kill tumor cells. Microtubule protein inhibitors, DNA damage agents, and RNA inhibitors are common cytotoxic molecules. Among these conjugates, cytotoxic molecules of natural origin are summarized based on their mechanism of action, conformational relationships, and the discovery of new derivatives. This paper also mentions some cytotoxic molecules that have the potential to be payloads. It also summarizes the latest technologies and novel conjugates developed in recent years to overcome the shortcomings of ADCs, PDCs, SMDCs, ApDCs, and VDCs. In addition, this paper summarizes the clinical trials conducted on conjugates of these cytotoxic molecules over the last five years. It provides a reference for designing and developing safer and more efficient conjugates.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S104366182400286X/pdfft?md5=ece0fb06ce50d4390a55adc761fda24c&pid=1-s2.0-S104366182400286X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971592","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}
Pub Date : 2024-08-10DOI: 10.1016/j.phrs.2024.107348
Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.
{"title":"CX3C chemokine: Hallmarks of fibrosis and ageing","authors":"","doi":"10.1016/j.phrs.2024.107348","DOIUrl":"10.1016/j.phrs.2024.107348","url":null,"abstract":"<div><p>Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002937/pdfft?md5=1f61b77fe18a76700c40f5d633ee5ce5&pid=1-s2.0-S1043661824002937-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971621","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}
Pub Date : 2024-08-09DOI: 10.1016/j.phrs.2024.107344
{"title":"Anti-amyloid immunotherapy in Alzheimer’s disease: The new dawn emerging from 179 clinical trials","authors":"","doi":"10.1016/j.phrs.2024.107344","DOIUrl":"10.1016/j.phrs.2024.107344","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002895/pdfft?md5=1b7ab48837dcb26f469f3d9939c5bd55&pid=1-s2.0-S1043661824002895-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913665","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}
Pub Date : 2024-08-08DOI: 10.1016/j.phrs.2024.107346
Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.
{"title":"CD31 orchestrates metabolic regulation in autophagy pathways of rheumatoid arthritis","authors":"","doi":"10.1016/j.phrs.2024.107346","DOIUrl":"10.1016/j.phrs.2024.107346","url":null,"abstract":"<div><p>Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002913/pdfft?md5=dabf912e4f260cf26f2e6c70992580c8&pid=1-s2.0-S1043661824002913-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913666","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}