J V Zhukova, J A Lopatnikova, A A Alshevskaya, S V Sennikov
{"title":"Molecular mechanisms of regulation of IL-1 and its receptors.","authors":"J V Zhukova, J A Lopatnikova, A A Alshevskaya, S V Sennikov","doi":"10.1016/j.cytogfr.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.09.004","url":null,"abstract":"<p><p>Interleukin 1 (IL-1) is a pro-inflammatory cytokine that plays a key role in the development and regulation of nonspecific defense and specific immunity. However, its regulatory influence extends beyond inflammation and impacts a range of immune and non-immune processes. The involvement of IL-1 in numerous biological processes, including modulation of inflammation, necessitates strict regulation at multiple levels. This review focuses on these regulatory processes and discusses their underlying mechanisms. IL-1 activity is controlled at various levels, including receptor binding, gene transcription, expression as inactive proforms, and regulated post-translational processing and secretion. Regulation at the level of the receptor expression - alternative splicing, tissue-specific isoforms, and gene polymorphism - is also crucial to IL-1 functional activity. Understanding these regulatory features of IL-1 will not only continue to shape future research directions but will also highlight promising therapeutic strategies to modulate the biological effects of IL-1.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460064","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}
Dequan Liu, Tian Li, Lei Liu, Xiangyu Che, Xiaorui Li, Chang Liu, Guangzhen Wu
{"title":"Adeno-associated virus therapies: Pioneering solutions for human genetic diseases.","authors":"Dequan Liu, Tian Li, Lei Liu, Xiangyu Che, Xiaorui Li, Chang Liu, Guangzhen Wu","doi":"10.1016/j.cytogfr.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.09.003","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) has emerged as a fundamental component in the gene therapy landscape, widely acknowledged for its effectiveness in therapeutic gene delivery. The success of AAV-based therapies, such as Luxturna and Zolgensma, underscores their potential as a leading vector in gene therapy. This article provides an in-depth review of the development and mechanisms of AAV vector-based therapies, offering a comprehensive analysis of the latest clinical trial outcomes in central nervous system (CNS) diseases, ocular conditions, and hemophilia, where AAV therapies have shown promising results. Additionally, we discusse the selection of administration methods and serotypes tailored to specific diseases. Our objective is to showcase the innovative applications and future potential of AAV-based gene therapy, laying the groundwork for continued clinical advancements.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343406","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}
Cheng Liu, Shutao Chen, Yu Zhang, Xinyi Zhou, Haiwei Wang, Qigui Wang, Xi Lan
{"title":"Mechanisms of Rho GTPases in regulating tumor proliferation, migration and invasion.","authors":"Cheng Liu, Shutao Chen, Yu Zhang, Xinyi Zhou, Haiwei Wang, Qigui Wang, Xi Lan","doi":"10.1016/j.cytogfr.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.09.002","url":null,"abstract":"<p><p>The occurrence of most cancers is due to the clonal proliferation of tumor cells, immune evasion, and the ability to spread to other body parts. Rho GTPases, a family of small GTPases, are key regulators of cytoskeleton reorganization and cell polarity. Additionally, Rho GTPases are key proteins that induce the proliferation and metastasis of tumor cells. This review focuses on the complex regulatory mechanisms of Rho GTPases, exploring their critical role in promoting tumor cell proliferation and dissemination. Regarding tumor cell proliferation, attention is given to the role of Rho GTPases in regulating the cell cycle and mitosis. In terms of tumor cell dissemination, the focus is on the role of Rho GTPases in regulating cell migration and invasion. Overall, this review elucidates the mechanisms of Rho GTPases members in the development of tumor cells, aiming to provide theoretical references for the treatment of mammalian tumor diseases and related applications.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343407","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}
Yan Liao,Wangzheqi Zhang,Miao Zhou,Chenglong Zhu,Zui Zou
{"title":"Ubiquitination in pyroptosis pathway: A potential therapeutic target for sepsis.","authors":"Yan Liao,Wangzheqi Zhang,Miao Zhou,Chenglong Zhu,Zui Zou","doi":"10.1016/j.cytogfr.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.09.001","url":null,"abstract":"Sepsis remains a significant clinical challenge, causing numerous deaths annually and representing a major global health burden. Pyroptosis, a unique form of programmed cell death characterized by cell lysis and the release of inflammatory mediators, is a crucial factor in the pathogenesis and progression of sepsis, septic shock, and organ dysfunction. Ubiquitination, a key post-translational modification influencing protein fate, has emerged as a promising target for managing various inflammatory conditions, including sepsis. This review integrates the current knowledge on sepsis, pyroptosis, and the ubiquitin system, focusing on the molecular mechanisms of ubiquitination within pyroptotic pathways activated during sepsis. By exploring how modulating ubiquitination can regulate pyroptosis and its associated inflammatory signaling pathways, this review provides insights into potential therapeutic strategies for sepsis, highlighting the need for further research into these complex molecular networks.","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"49 1","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260121","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}
Francesca Coperchini, Alessia Greco, Marsida Teliti, Laura Croce, Spyridon Chytiris, Flavia Magri, Carlo Gaetano, Mario Rotondi
{"title":"Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing.","authors":"Francesca Coperchini, Alessia Greco, Marsida Teliti, Laura Croce, Spyridon Chytiris, Flavia Magri, Carlo Gaetano, Mario Rotondi","doi":"10.1016/j.cytogfr.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.cytogfr.2024.08.004","url":null,"abstract":"<p><p>Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the \"Hallmarks of ageing\". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.</p>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139581","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":"A quartet of cancer stem cell niches in hepatocellular carcinoma","authors":"Neha Balaji, Samiksha Kukal , Anjali Bhat , Nikita Pradhan, Shilpi Minocha, Saran Kumar","doi":"10.1016/j.cytogfr.2024.08.007","DOIUrl":"10.1016/j.cytogfr.2024.08.007","url":null,"abstract":"<div><p>Hepatocellular Carcinoma (HCC), the most prevalent type of primary liver cancer, is known for its aggressive behavior and poor prognosis. The Cancer Stem Cell theory, which postulates the presence of a small population of self-renewing cells called Cancer Stem Cells (CSCs), provides insights into various clinical and molecular features of HCC such as tumor heterogeneity, metabolic adaptability, therapy resistance, and recurrence. These CSCs are nurtured in the tumor microenvironment (TME), where a mix of internal and external factors creates a tumor-supportive niche that is continuously evolving both spatially and temporally, thus enhancing the tumor's complexity. This review details the origins of hepatic CSCs (HCSCs) and the factors influencing their stem-like qualities. It highlights the reciprocal crosstalk between HCSCs and the TME (hypoxic, vascular, invasive, and immune niches), exploring the signaling pathways involved and how these interactions control the malignant traits of CSCs. Additionally, it discusses potential therapeutic approaches targeting the HCSC niche and their possible uses in clinical practice.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 39-51"},"PeriodicalIF":9.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105251","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}
Paulina Kaminska , Aleksandra Tempes , Ela Scholz , Anna R. Malik
{"title":"Cytokines on the way to secretion","authors":"Paulina Kaminska , Aleksandra Tempes , Ela Scholz , Anna R. Malik","doi":"10.1016/j.cytogfr.2024.08.003","DOIUrl":"10.1016/j.cytogfr.2024.08.003","url":null,"abstract":"<div><p>The activation of immune cells by pro-inflammatory or immunosuppressive stimuli is followed by the secretion of immunoregulatory cytokines which serve as messengers to activate the immune response in target cells. Although the mechanisms that control the secretion of cytokines by immune cells are not yet fully understood, several key aspects of this process have recently emerged. This review focuses on cytokine release via exocytosis and highlights the routes of cytokine trafficking leading to constitutive and regulated secretion as well as the impact of sorting receptors on this process. We discuss the involvement of cytoskeletal rearrangements in vesicular transport, secretion, and formation of immunological synapses. Finally, we describe the non-classical pathways of cytokine release that are independent of vesicular ER-Golgi transport. Instead, these pathways are based on processing by inflammasome or autophagic mechanisms. Ultimately, understanding the molecular mechanisms behind cytokine release may help to identify potential therapeutic targets in diseases associated with altered immune responses.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 52-65"},"PeriodicalIF":9.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359610124000637/pdfft?md5=8a583e9a03d3ff4f92895bd11a743f84&pid=1-s2.0-S1359610124000637-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125112","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":"Biomarker discovery in hepatocellular carcinoma (HCC) for personalized treatment and enhanced prognosis","authors":"Baofa Yu , Wenxue Ma","doi":"10.1016/j.cytogfr.2024.08.006","DOIUrl":"10.1016/j.cytogfr.2024.08.006","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is a leading contributor to cancer-related deaths worldwide and presents significant challenges in diagnosis and treatment due to its heterogeneous nature. The discovery of biomarkers has become crucial in addressing these challenges, promising early detection, precise diagnosis, and personalized treatment plans. Key biomarkers, such as alpha fetoprotein (AFP) glypican 3 (GPC3) and des gamma carboxy prothrombin (DCP) have shown potential in improving clinical results. Progress in proteomic technologies, including next-generation sequencing (NGS), mass spectrometry, and liquid biopsies detecting circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), has deepened our understanding of HCC’s molecular landscape. Immunological markers, like PD-L1 expression and tumor-infiltrating lymphocytes (TILs), also play a crucial role in guiding immunotherapy decisions. Despite these advancements, challenges remain in biomarker validation, standardization, integration into clinical practice, and cost-related barriers. Emerging technologies like single-cell sequencing and machine learning offer promising avenues for further exploration. Continued investment in research and collaboration among researchers, healthcare providers, and policymakers is vital to harness the potential of biomarkers fully, ultimately revolutionizing HCC management and improving patient outcomes through personalized treatment approaches.</p></div>","PeriodicalId":11132,"journal":{"name":"Cytokine & Growth Factor Reviews","volume":"79 ","pages":"Pages 29-38"},"PeriodicalIF":9.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079589","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":"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}