{"title":"Interferon-I modulation and natural products: Unraveling mechanisms and therapeutic potential in severe COVID-19.","authors":"Yuheng Song,Jiani Lu,Pengcheng Qin,Hongzhuan Chen,Lili Chen","doi":"10.1016/j.cytogfr.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.08.005","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a significant global public health threat, particularly to older adults, pregnant women, and individuals with underlying chronic conditions. Dysregulated immune responses to SARS-CoV-2 infection are believed to contribute to the progression of COVID-19 in severe cases. Previous studies indicates that a deficiency in type I interferon (IFN-I) immunity accounts for approximately 15 %-20 % of patients with severe pneumonia caused by COVID-19, highlighting the potential therapeutic importance of modulating IFN-I signals. Natural products and their derivatives, due to their structural diversity and novel scaffolds, play a crucial role in drug discovery. Some of these natural products targeting IFN-I have demonstrated applications in infectious diseases and inflammatory conditions. However, the immunomodulatory potential of IFN-I in critical COVID-19 pneumonia and the natural compounds regulating the related signal pathway remain not fully understood. In this review, we offer a comprehensive assessment of the association between IFN-I and severe COVID-19, exploring its mechanisms and integrating information on natural compounds effective for IFN-I regulation. Focusing on the primary targets of IFN-I, we also summarize the regulatory mechanisms of natural products, their impact on IFNs, and their therapeutic roles in viral infections. Collectively, by synthesizing these findings, our goal is to provide a valuable reference for future research and to inspire innovative treatment strategies for COVID-19.","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"18 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Altijana Hromić-Jahjefendić, Lejla Mahmutović, Abas Sezer, Tea Bećirević, Alberto Rubio-Casillas, Elrashdy M Redwan, Vladimir N Uversky
{"title":"The intersection of microbiome and autoimmunity in long COVID-19: Current insights and future directions.","authors":"Altijana Hromić-Jahjefendić, Lejla Mahmutović, Abas Sezer, Tea Bećirević, Alberto Rubio-Casillas, Elrashdy M Redwan, Vladimir N Uversky","doi":"10.1016/j.cytogfr.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.08.002","url":null,"abstract":"<p><p>Long COVID-19 affects a significant percentage of patients and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system referring to the ability of immune system to constantly monitor the body for signs of infection, disease, or abnormal cells; altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes-interventions that target the microbiome-may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. More research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Songyu Shen , Yihan Hong , Jiajun Huang , Xiaosheng Qu , Suren Rao Sooranna , Sheng Lu , Tian Li , Bing Niu
{"title":"Targeting PD-1/PD-L1 in tumor immunotherapy: Mechanisms and interactions with host growth regulatory pathways","authors":"Songyu Shen , Yihan Hong , Jiajun Huang , Xiaosheng Qu , Suren Rao Sooranna , Sheng Lu , Tian Li , Bing Niu","doi":"10.1016/j.cytogfr.2024.08.001","DOIUrl":"10.1016/j.cytogfr.2024.08.001","url":null,"abstract":"<div><p>Tumor immunotherapy has garnered considerable attention, emerging as a new standard of care in cancer treatment. The conventional targets, such as VEGF and EGFR, have been extended to others including BRAF and PD-1/PD-L1, which have shown significant potential in recent cancer treatments. This review aims to succinctly overview the impact and mechanisms of therapies that modulate PD-1/PD-L1 expression by targeting VEGF, EGFR, LAG-3, CTLA-4 and BRAF. We investigated how modulation of PD-1/PD-L1 expression impacts growth factor signaling, shedding light on the interplay between immunomodulatory pathways and growth factor networks within the tumor microenvironment. By elucidating these interactions, we aim to provide insights into novel potential synergistic therapeutic strategies for cancer immunotherapy.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 16-28"},"PeriodicalIF":9.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zihan Chen , Ping Jiang , Dan Su , Yu Zhao , Mingming Zhang
{"title":"Therapeutic inhibition of the JAK-STAT pathway in the treatment of inflammatory bowel disease","authors":"Zihan Chen , Ping Jiang , Dan Su , Yu Zhao , Mingming Zhang","doi":"10.1016/j.cytogfr.2024.07.008","DOIUrl":"10.1016/j.cytogfr.2024.07.008","url":null,"abstract":"<div><p>Inflammatory bowel disease (IBD) encompasses a group of non-specific chronic intestinal inflammatory conditions of unclear etiology. The current treatment and long-term management primarily involve biologics. Nevertheless, some patients experience treatment failure or intolerance to biologics [1], making these patients a primary focus of IBD research. The Janus kinase (JAK)-Signal Transducers and Activator of Transcription (STAT) signal transduction pathway is crucial to the regulation of immune and inflammatory responses [2], and plays an important role in the pathogenesis of IBD. JAK inhibitors alleviate IBD by suppressing the transmission of JAK-STAT signaling pathway. As the first small-molecule oral inhibitor for IBD, JAK inhibitors greatly improved the treatment of IBD and have demonstrated significant efficacy, with tofacitinib and upadacitinib being approved for the treatment of ulcerative colitis (UC) [3]. JAK inhibitors can effectively alleviate intestinal inflammation in IBD patients who have failed to receive biologics, which may bring new treatment opportunities for refractory IBD patients. This review aims to elucidate the crucial roles of JAK-STAT signal transduction pathway in IBD pathogenesis, examine its role in various cell types within IBD, and explore the research progress of JAK inhibitors as therapeutic agents, paving the road for new IBD treatment strategies.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 1-15"},"PeriodicalIF":9.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuqin Zhang , Lin Liu , Lixia Yue , Yongzhuo Huang , Bing Wang , Peifeng Liu
{"title":"Uncovering key mechanisms and intervention therapies in aging skin","authors":"Yuqin Zhang , Lin Liu , Lixia Yue , Yongzhuo Huang , Bing Wang , Peifeng Liu","doi":"10.1016/j.cytogfr.2024.07.009","DOIUrl":"10.1016/j.cytogfr.2024.07.009","url":null,"abstract":"<div><p>Advancements in understanding skin aging mechanisms, which encompass both external and internal aging processes, have spurred the development of innovative treatments primarily aimed at improving cosmetic appearance. These findings offer the potential for the development of novel therapeutic strategies aimed at achieving long-term, non-therapy-dependent clinical benefits, including the reversal of aging and the mitigation of associated health conditions. Realizing this goal requires further research to establish the safety and efficacy of targeting aging-related skin changes, such as pigmentation, wrinkling, and collagen loss. Systematic investigation is needed to identify the most effective interventions and determine optimal anti-aging treatment strategies. These reviews highlight the features and possible mechanisms of skin aging, as well as the latest progress and future direction of skin aging research, to provide a theoretical basis for new practical anti-skin aging strategies.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 66-80"},"PeriodicalIF":9.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial and macrophage interactions in the angiogenic niche","authors":"Fahad Hassan Shah, Heon-Woo Lee","doi":"10.1016/j.cytogfr.2024.07.005","DOIUrl":"10.1016/j.cytogfr.2024.07.005","url":null,"abstract":"<div><p>The interactions between vascular cells, especially endothelial cells, and macrophages play a pivotal role in maintaining the subtle balance of vascular biology, which is crucial for angiogenesis in both healthy and diseased states. These cells are central to ensuring a harmonious balance between tissue repair and preventing excessive angiogenic activity, which could lead to pathological conditions. Recent advances in sophisticated genetic engineering vivo models and novel sequencing approaches, such as single-cell RNA-sequencing, in immunobiology have significantly enhanced our understanding of the gene expression and behavior of macrophages. These insights offer new perspectives on the role macrophages play not only in development but also across various health conditions. In this review, we explore the complex interactions between multiple types of macrophages and endothelium, focusing on their impact on new blood vessel formation. By understanding these intricate interactions, we aim to provide insights into new methods for managing angiogenesis in various diseases, thereby offering hope for the development of novel therapeutic approaches.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"78 ","pages":"Pages 64-76"},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gustav van Niekerk, Lotte Coelmont, Yeranddy A. Alpizar, Lara Kelchtermans, Elias Broeckhoven, Kai Dallmeier
{"title":"GLP-1R agonist therapy and vaccine response: Neglected implications","authors":"Gustav van Niekerk, Lotte Coelmont, Yeranddy A. Alpizar, Lara Kelchtermans, Elias Broeckhoven, Kai Dallmeier","doi":"10.1016/j.cytogfr.2024.07.006","DOIUrl":"10.1016/j.cytogfr.2024.07.006","url":null,"abstract":"<div><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide (Ozempic®), have emerged as effective treatments for diabetes and weight management. However, recent evidence indicates that GLP-1R signalling influences various tissues, including the immune system. Notably, GLP-1 has a short half-life (< 5 minutes) and exists in the picomolar range, while GLP-1RAs like semaglutide have extended half-lives of several days and are administered at supraphysiological doses. This review explores the potential impact of these medications on vaccine efficacy. We examine evidence suggesting that GLP-1RAs may attenuate vaccine responses through direct effects on immune cells and modulation of other tissues. Additionally, we discuss how GLP-1R signalling may create a tolerogenic environment, potentially reducing vaccine immunogenicity. Given the widespread use of GLP-1RAs, it is crucial to understand their impact on immune responses and the translational implications for vaccination outcomes.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"78 ","pages":"Pages 14-24"},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610124000492/pdfft?md5=134da4eb9801a43d1cd7946efec687b5&pid=1-s2.0-S1359610124000492-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141711587","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}
{"title":"The impact of cytokines in neuroinflammation-mediated stroke","authors":"Sneha Kumari , Rishika Dhapola , Prajjwal Sharma , Pushank Nagar , Bikash Medhi , Dibbanti HariKrishnaReddy","doi":"10.1016/j.cytogfr.2024.06.002","DOIUrl":"10.1016/j.cytogfr.2024.06.002","url":null,"abstract":"<div><p>Cerebral stroke is ranked as the third most common contributor to global mortality and disability. The involvement of inflammatory mechanisms, both peripherally and within the CNS, holds significance in the pathophysiological cascades following the initiation of stroke. After the onset of acute stroke, predominantly ischemic, a subsequent phase of neuroinflammation ensues. It is a dual-effect process that not only exacerbates injury, leading to cell death, but paradoxically, it also serves a shielding role in facilitating recovery. Cytokines serve as pivotal mediators within the inflammatory cascade, actively contributing to the progression of ischemic damage. Stroke is followed by increased expression of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, etc. leading to the recruitment and stimulation of glial cells and peripheral leukocytes at the site of injury, promoting neuroinflammation. Cytokines can directly induce neuronal injury and death through various mechanisms, including excitotoxicity, oxidative stress, HPA-axis activation, secretion of matrix metalloproteinase and apoptosis. They can also amplify the inflammatory response, leading to further neuronal damage. Therapeutic strategies aimed at modulating cytokine release, immune response and cytokine signalling or activity are being explored as potential interventions to mitigate neuroinflammation and its detrimental effects in stroke. In this review, we have given a concise summary of our current knowledge of the function of various cytokines, brain inflammation and various signalling and molecular pathways including JAK/STAT3, TGF-β/Smad, MAPK, HMGB1/TLR and NF-κB modulated cytokines regulation in stroke. Therapeutic agents such as MCC950, genistein, edaravone, minocycline, etc. targeting various cytokines-associated signalling pathways have shown efficacy in preclinical and clinical trials reducing the pathophysiology of the illness were also addressed in this study.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"78 ","pages":"Pages 105-119"},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The anti-inflammatory effects of itaconate and its derivatives in neurological disorders","authors":"","doi":"10.1016/j.cytogfr.2024.07.001","DOIUrl":"10.1016/j.cytogfr.2024.07.001","url":null,"abstract":"<div><p>Almost 16 % of the global population is affected by neurological disorders, including neurodegenerative and cerebral neuroimmune diseases, triggered by acute or chronic inflammation. Neuroinflammation is recognized as a common pathogenic mechanism in a wide array of neurological conditions including Alzheimer's disease, Parkinson's disease, postoperative cognitive dysfunction, stroke, traumatic brain injury, and multiple sclerosis. Inflammatory process in the central nervous system (CNS) can lead to neuronal damage and neuronal apoptosis, consequently exacerbating these diseases. Itaconate, an immunomodulatory metabolite from the tricarboxylic acid cycle, suppresses neuroinflammation and modulates the CNS immune response. Emerging human studies suggest that itaconate levels in plasma and cerebrospinal fluid may serve as biomarkers associated with inflammatory responses in neurological disorders. Preclinical studies have shown that itaconate and its highly cell-permeable derivatives are promising candidates for preventing and treating neuroinflammation-related neurological disorders. The underlying mechanism may involve the regulation of immune cells in the CNS and neuroinflammation-related signaling pathways and molecules including Nrf2/KEAP1 signaling pathway, reactive oxygen species, and NLRP3 inflammasome. Here, we introduce the metabolism and function of itaconate and the synthesis and development of its derivatives. We summarize the potential impact and therapeutic potential of itaconate and its derivatives on brain immune cells and the associated signaling pathways and molecules, based on preclinical evidence via various neurological disorder models. We also discuss the challenges and potential solutions for clinical translation to promote further research on itaconate and its derivatives for neuroinflammation-related neurological disorders.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"78 ","pages":"Pages 37-49"},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610124000455/pdfft?md5=18df5660e3fcec7871f71ba6e83ec6ce&pid=1-s2.0-S1359610124000455-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562924","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}
Mateusz A. Krzyscik , Kelly Karl , Pooja Dudeja , Pavel Krejci , Kalina Hristova
{"title":"Quantitative and qualitative differences in the activation of a fibroblast growth factor receptor by different FGF ligands","authors":"Mateusz A. Krzyscik , Kelly Karl , Pooja Dudeja , Pavel Krejci , Kalina Hristova","doi":"10.1016/j.cytogfr.2024.07.002","DOIUrl":"10.1016/j.cytogfr.2024.07.002","url":null,"abstract":"<div><p><span><span>The FGF<span> system is the most complex of all receptor tyrosine kinase signaling networks with </span></span>18 FGF<span><span> ligands and four FGFRs that deliver morphogenic signals to pattern most embryonic structures. Even when a single FGFR is expressed in the tissue, different FGFs can trigger dramatically different biological responses via this receptor. Here we show both quantitative and qualitative differences in the signaling of one of the FGF receptors, FGFR1c, in response to different FGFs. We provide an overview of the recent discovery that FGFs engage in biased signaling via FGFR1c. We discuss the concept of ligand bias, which represents qualitative differences in signaling as it is a measure of differential ligand preferences for different downstream responses. We show how FGF ligand bias manifests in functional data in cultured </span>chondrocyte cells. We argue that FGF-ligand bias contributes substantially to FGF-driven developmental processes, along with known differences in FGF expression levels, FGF-FGFR binding coefficients and differences in FGF stability </span></span><em>in vivo</em>.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"78 ","pages":"Pages 77-84"},"PeriodicalIF":9.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141710964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}