Frontiers in bioscience (Landmark edition)最新文献

{"title":"Improvement of RSV-Induced Asthma in Mice: A Study Based on Icariin-Mediated PD-1.","authors":"Jiayao Fu, Xiaohong Wang","doi":"10.31083/FBL26061","DOIUrl":"https://doi.org/10.31083/FBL26061","url":null,"abstract":"<p><strong>Background: </strong>Infection with respiratory syncytial virus (RSV) has the potential to exacerbate asthma by causing prolonged inflammation in the airways. Mounting evidence has revealed the significant involvement of programmed cell death protein-1 (PD-1) in the development of asthma. Although icariin (IC) has shown potential in improving airway remodeling in ovalbumin (OVA)-induced asthma, its impact and underlying mechanisms in cases of asthma aggravated by RSV infection are not thoroughly understood.</p><p><strong>Objective: </strong>To explore the effect of IC on RSV-infected asthmatic mice and the mechanism involving PD-1.</p><p><strong>Methods: </strong>A model of asthmatic mice infected with RSV was developed. To evaluate the effects of IC treatment, general behavioral characterization, histopathologic analysis, bronchoalveolar lavage fluid (BALF) analysis, and enzyme-linked immunosorbent assays (ELISA) were performed to assess the frequency of sneezing and nose scratching, the content of OVA-specific IgE, oxidative stress and airway inflammation in mice. Apoptosis was also assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Finally, the expression levels of apoptosis protein, oxidative stress-related protein, and PD-1 were assessed by western blot.</p><p><strong>Results: </strong>IC significantly ameliorated the sneezing and nose-scratching frequency (<i>p</i> < 0.001) and decreased OVA-specific IgE levels in asthmatic mice infected with RSV (<i>p</i> < 0.01). IC treatment remarkably reduced the infiltration of inflammatory cells around the alveoli and lowered the overall inflammation score. It also notably decreased the levels of inflammatory cytokines interleukin-4 (IL-4), IL-13, and IL-5, and decreased the numbers of neutrophils, eosinophils, and macrophages in the bronchoalveolar lavage fluid (BALF) (<i>p</i> < 0.001). IC ameliorated oxidative stress in RSV-infected asthmatic mice (<i>p</i> < 0.001). In addition, IC reduced apoptosis while increasing PD-1 expression in asthmatic mice infected with RSV (<i>p</i> < 0.001). Interestingly, si-PD-1 significantly reversed IC inhibition of inflammatory cytokines and apoptosis-related proteins, and promoted PD-1 protein expression (<i>p</i> < 0.01). The findings suggested that IC might be effective in alleviating asthma triggered by RSV in mice by regulating the expression of PD-1.</p><p><strong>Conclusion: </strong>IC ameliorated RSV-induced asthma in mice by regulating PD-1 expression, and may hold promise as a potential therapeutic agent for RSV-induced asthma in mice. These findings provide valuable insights into the possibility of using IC as a treatment option for asthma caused by RSV.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26061"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid-Derived Suppressor Cells: Implications in Cancer Immunology and Immunotherapy.","authors":"Juan F Santibanez","doi":"10.31083/FBL25203","DOIUrl":"https://doi.org/10.31083/FBL25203","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSCs) are believed to be key promoters of tumor development and are recognized as a hallmark of cancer cells' ability to evade the immune system evasion. MDSC levels often increase in peripheral blood and the tumor microenvironment (TME). These cells exert immunosuppressive functions, weakening the anticancer immune surveillance system, in part by repressing T-cell immunity. Moreover, MDSCs may promote tumor progression and interact with cancer cells, increasing MDSC expansion and favoring an immunotolerant TME. This review analyzes the primary roles of MDSCs in cancer and T-cell immunity, discusses the urgent need to develop effective MDSC-targeted therapies, and highlights the potential synergistic combination of MDSC targeting with chimeric antigen receptors and immune checkpoint inhibitors.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"25203"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Extracellular Vesicles Promote HBV Replication via METTL3-IGF2BP2-Mediated m6A Modification.","authors":"Jie Zhang, Ling Yu, Xinyu Wu, Wanlong Pan","doi":"10.31083/FBL36291","DOIUrl":"https://doi.org/10.31083/FBL36291","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The roles of small extracellular vesicles (sEVs) and mRNA modifications in regulating hepatitis B virus (HBV) transmission, replication, and related disease progression have received considerable attention. However, the mechanisms through which methyltransferase-like 3 (&lt;i&gt;METTL3&lt;/i&gt;) and insulin-like growth factor 2 (&lt;i&gt;IGF2BP2&lt;/i&gt;), key genes that mediate m6A modifications, regulate HBV replication in sEVs remain poorly understood. Therefore, this study investigated the molecular mechanisms through which the key molecules (&lt;i&gt;METTL3&lt;/i&gt; and &lt;i&gt;IGF2BP2&lt;/i&gt;) in sEVs mediate m6A epigenetic modification to regulate HBV replication.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Small extracellular vesicles were extracted from the supernatants of HepG2.2.15 and HepG2 cells via ultracentrifugation, followed by purification with hepatitis B virus surface antigen (&lt;i&gt;HepBsAg&lt;/i&gt;) immunomagnetic beads. The sEVs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and Western blotting (WB). Methylation enrichment in the two types of sEVs was analyzed by dot blotting and quantitative reverse transcription-PCR (RT-qPCR). The cells were treated with HepG2.2.15-sEVs transfected with either the &lt;i&gt;METTL3&lt;/i&gt; plasmid, &lt;i&gt;METTL3&lt;/i&gt; siRNA, the &lt;i&gt;IGF2BP2&lt;/i&gt; plasmid, or the &lt;i&gt;IGF2BP2&lt;/i&gt; siRNA. After 48 h, the expression of &lt;i&gt;METTL3&lt;/i&gt;, &lt;i&gt;IGF2BP2&lt;/i&gt;, and &lt;i&gt;HBV DNA&lt;/i&gt; expressions were assessed via dot blotting, quantitative-PCR (qPCR), RT-qPCR, and WB. Co-immunoprecipitation (co-IP) was performed to investigate the interactions between METTL3 and IGF2BP2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;By conducting TEM, DLS, and WB analyses, we confirmed that the isolated sEVs exhibited typical characteristics. HepG2.2.15-derived sEVs presented elevated levels of m6A modifications, with increased &lt;i&gt;METTL3&lt;/i&gt; and &lt;i&gt;IGF2BP2&lt;/i&gt; mRNA and protein expression levels, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). In the overexpression (OE)-METTL3 group, the expression levels of HBV pregenomic RNA (&lt;i&gt;HBV pgRNA&lt;/i&gt;), &lt;i&gt;HBV DNA&lt;/i&gt;, HBV relaxed circular DNA (&lt;i&gt;HBV rcDNA&lt;/i&gt;), HBV covalently closed circular DNA (&lt;i&gt;HBV cccDNA&lt;/i&gt;), &lt;i&gt;HBsAg&lt;/i&gt;, hepatitis B virus core antigen (&lt;i&gt;HBcAg&lt;/i&gt;), and hepatitis B virus e antigen (&lt;i&gt;HBeAg&lt;/i&gt;) were significantly elevated compared to those in the control group (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). In contrast, results for the small interfering (SI)-METTL3 group were the opposite. Similarly, in the OE-IGF2BP2 group, &lt;i&gt;HBV pgRNA&lt;/i&gt;, &lt;i&gt;HBV DNA&lt;/i&gt;, &lt;i&gt;HBV rcDNA&lt;/i&gt;, &lt;i&gt;HBV cccDNA&lt;/i&gt;, &lt;i&gt;HBsAg&lt;/i&gt;, &lt;i&gt;HBcAg&lt;/i&gt;, and &lt;i&gt;HBeAg&lt;/i&gt; expression were greater than in the control group (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), whereas the opposite results were recorded in the SI-IGF2BP2 group. Co-immunoprecipitation confirmed that METTL3 and IGF2BP2 interact synergistically.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Small extracellular vesicles increase &lt;i&gt;METTL3&lt;/i&gt; and &lt;i&gt;IGF2BP2&lt;/i&gt; expression, synergistically promoting HBV replication by re","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36291"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukemia Inhibitory Factor Attenuates Hypoxic-Ischemic White Matter Injury via NLRP3 Inflammasome Activity Suppressing Through the Nrf2/HO-1 Pathway.","authors":"Liang Huo, Xueyan Liu, Hua Wang","doi":"10.31083/FBL36630","DOIUrl":"https://doi.org/10.31083/FBL36630","url":null,"abstract":"<p><strong>Background: </strong>Inhibiting neuroinflammatory damage is an effective strategy for treating preterm white matter injury (PWMI). Leukemia inhibitory factor (LIF) can ameliorate (HI) induced white matter injury; however, the neuroprotective effects and mechanisms of LIF remain unclear. This study aimed to determine whether NOD-like receptor thermal protein domain associated protein (NLRP3)-dependent pyroptosis is involved in PWMI pathogenesis.</p><p><strong>Methods: </strong>We established an <i>in vitro</i> oxygen-glucose deprivation (OGD) cell model and an <i>in vivo</i> HI induced brain white matter injury neonatal mouse model. RNA sequencing (RNA-seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses examined differentially expressed genes in oxygen-glucose deprivation/reoxygenation (OGD/R) challenged CTX TNA2 rat astrocytes. The changes and effects of proteins were confirmed in neonatal rats <i>in vitro</i> and <i>in vivo</i>. Cell viability assays, reactive oxygen species (ROS) assays, apoptosis assays, and immunoblot were used to confirm LIF-mediated its neuroprotective effect against HI-induced white matter injury <i>in vitro</i>.</p><p><strong>Results: </strong>RNA-seq and KEGG analyses indicated OGD/R enriched NLRP3 inflammasome-related genes (validated by <i>in vitro</i> and <i>in vivo</i> models), showing that NLRP3-dependent pyroptosis proteins (apoptosis-associated speck-like protein contain a CARD (ASC), NLRP3, active caspase 1, IL-1β, IL-18, and N-terminal fragment of gasdermin D (GSDMD-N)) were all increased by HI or OGD/R. LIF upregulated HO-1 expression by activating Nrf2 via the MAPK and Akt kinase pathways and significantly decreased OGD/R-induced ROS production. NLRP3-dependent pyroptosis proteins were suppressed in the LIF group compared with those in the OGD/R and HI groups. Zinc protophyrin, an HO-1 inhibitor, partially abolished LIF-mediated viability enhancement in rat astrocytes.</p><p><strong>Conclusion: </strong>NLRP3-dependent pyroptosis plays a role in PWMI pathogenesis; moreover, LIF mitigates OGD/R-induced pyroptosis-dependent neurotoxicity by upregulating HO-1 expression in rat astrocytes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36630"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription Factor FOSL1 Promotes Cisplatin Resistance in Non-Small Cell Lung Cancer Cells by Modulating the Wnt3a/β-Catenin Signaling through Upregulation of PLIN3 Expression.","authors":"Wanning Tong, Jianjun Sun, Bin Shen, Yaohua Hu, Chenxing Wang, Min Rao, Jin Li, Delin Xia, Jiagui Dong, Hong Wang, Dongmei Zhu, Haibo Wu, Zhigang Cai","doi":"10.31083/FBL26898","DOIUrl":"https://doi.org/10.31083/FBL26898","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, accounting for 45.3% of all cases and serving as a major cause of cancer-related mortality. Although cisplatin (DDP) is a cornerstone in LUAD therapy, its efficacy is often compromised by resistance, leading to therapeutic failure and poor patient outcomes. Lipid metabolism and associated proteins, such as perilipin 3 (PLIN3), have been increasingly implicated in cancer progression and chemoresistance. However, the precise mechanisms through which PLIN3 contributes to cisplatin (DDP) resistance in LUAD remain poorly understood.</p><p><strong>Methods: </strong>To investigate the role of PLIN3 in DDP resistance, its expression in LUAD tissues and its correlation with patient prognosis were analyzed using bioinformatics databases and validated through clinical sample analysis. The effects of <i>PLIN3</i> knockdown and overexpression on DDP resistance and Wnt3a/β-catenin signaling were assessed using quantitative real-time PCR (qPCR), western blotting, cytotoxicity assays, and colony formation assays. Bioinformatics screening identified FOS-like antigen 1 (FOSL1) as a transcription factor positively correlated with PLIN3, and its involvement in DDP resistance was further examined both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>PLIN3 expression is significantly elevated in LUAD tissues and correlates with poor overall survival. In LUAD cells, PLIN3 overexpression enhanced DDP resistance by upregulating Wnt3a expression and promoting β-catenin nuclear translocation. Bioinformatics analysis identified FOSL1 as a key transcription factor regulating PLIN3 expression. Experimental validation confirmed that FOSL1 directly binds to the PLIN3 promoter, activating the Wnt3a/β-catenin pathway and promoting DDP resistance. Knockdown of PLIN3 or inhibition of Wnt3a signaling reversed the effects of FOSL1 overexpression on DDP resistance.</p><p><strong>Conclusion: </strong>This study demonstrates that PLIN3 contributes to DDP resistance in LUAD by activating the Wnt3a/β-catenin signaling pathway, with FOSL1 acting as a critical upstream regulator. Targeting the FOSL1/PLIN3/Wnt/β-catenin axis may provide a promising therapeutic strategy for overcoming chemoresistance in LUAD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26898"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An MRI Radiogenomic Signature to Characterize the Transcriptional Heterogeneity Associated with Prognosis and Biological Functions in Glioblastoma.","authors":"Xiaoqing Zhang, Xiaoyu Zhang, Jie Zhu, Zhuoya Yi, Huijiao Cao, Hailin Tang, Huan Zhang, Guoxian Huang","doi":"10.31083/FBL36348","DOIUrl":"https://doi.org/10.31083/FBL36348","url":null,"abstract":"<p><strong>Background: </strong>The study sought to establish a radiogenomic signature to evaluate the transcriptional heterogeneity that reflects the prognosis and tumour-related biological functions of patients with glioblastoma.</p><p><strong>Methods: </strong>Transcriptional subclones were identified via fully unsupervised deconvolution of RNA sequencing. A genomic prognostic risk score was developed from transcriptional subclone proportions in the development dataset (n = 532) and independently verified in the testing dataset (n = 225). Multimodal magnetic resonance imaging (MRI) analysis involved feature extraction from three distinct anatomical regions across four imaging sequences. Key features were selected to construct a radiogenomic signature predictive of the genomic risk score in the radiogenomic dataset (n = 99), with subsequent survival analysis conducted in the image testing dataset (n = 233).</p><p><strong>Results: </strong>A total of 8 transcriptional subclones were identified, of which the metabolic pathway subclone and spinocerebellar ataxia subclone were independent risk factors for overall survival. The genomic risk score effectively differentiated patient subgroups with divergent survival outcomes in both development (<i>p</i> < 0.001) and testing datasets (<i>p</i> = 0.0003). Nineteen radiomic features were selected to construct a radiogenomic signature, with these features being linked to hallmark cancer pathways and the malignant behaviours of cancer cells. The radiogenomic signature predicted overall survival in the image testing dataset (hazard ratios (HR) = 1.67, <i>p</i> = 0.011).</p><p><strong>Conclusions: </strong>A prognostic radiogenomic signature was established and verified to characterize transcriptional subclones with underlying biological functions in glioblastoma.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"36348"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay Between Polyphenols and Autophagy: Insights From an Aging Perspective.","authors":"Alejandro Ponce-Mora, Nicolle Andrea Salazar, Alicia Domenech-Bendaña, Antonella Locascio, Eloy Bejarano, Lucia Gimeno-Mallench","doi":"10.31083/FBL25728","DOIUrl":"https://doi.org/10.31083/FBL25728","url":null,"abstract":"<p><p>The relationship between polyphenols and autophagy, particularly in the context of aging, presents a promising avenue for therapeutic interventions in age-related diseases. A decline in autophagy is associated with aging-related affections, and an increasing number of studies suggest that this enhancement is linked to cellular resilience and longevity. This review delves into the multifaceted roles of autophagy in cellular homeostasis and the potential of polyphenols to modulate autophagic pathways. We revised the most updated literature regarding the modulatory effects of polyphenols on autophagy in cardiovascular, liver, and kidney diseases, highlighting their therapeutic potential. We highlight the role of polyphenols as modulators of autophagy to combat age-related diseases, thus contributing to improving the quality of life in aging populations. A better understanding of the interplay of autophagy between autophagy and polyphenols will help pave the way for future research and clinical applications in the field of longevity medicine.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"25728"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Therapeutic Agents and Nanotechnology-Driven Innovations in Psoriasis Management.","authors":"Tarnjot Kaur, Nikita Hinge, Sudeep Pukale, Mohd Nazam Ansari, Kamal Y Thajudeen, Mukesh Nandave, Jyoti Upadhyay","doi":"10.31083/FBL27910","DOIUrl":"https://doi.org/10.31083/FBL27910","url":null,"abstract":"<p><p>Psoriasis has been a rising concern for over a decade, imposing significant challenges to individuals and society. Traditional topical therapy is non-targeted and acts systemically, with associated side effects. This increases the global burden both socially and economically. This review covers the evolution of drug molecules and nanotechnology-based approaches for the topical treatment of psoriasis, a chronic inflammatory skin disorder with no known etiology. Nanotechnology-based approaches offer promising solutions by reducing side effects, providing targeted delivery, protecting drug molecules from degradation, enhancing skin retention, and providing controlled release. Researchers have investigated the incorporation of various conventional and non-conventional therapeutic agents into nanocarriers for psoriasis treatment. The current understanding of the disease and its treatment using various therapeutic agents combined with novel formulation strategies will reduce the duration of treatment and improve the quality of life in psoriatic disease conditions.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"27910"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin Ligases in Control: Regulating NLRP3 Inflammasome Activation.","authors":"Swarna Beesetti","doi":"10.31083/FBL25970","DOIUrl":"https://doi.org/10.31083/FBL25970","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Ubiquitin ligases play pivotal roles in the regulation of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, a critical process in innate immunity and inflammatory responses. This review explores the intricate mechanisms by which various E3 ubiquitin ligases exert both positive and negative influences on NLRP3 inflammasome activity through diverse post-translational modifications. Negative regulation of NLRP3 inflammasome assembly is mediated by several E3 ligases, including F-box and leucine-rich repeat protein 2 (FBXL2), tripartite motif-containing protein 31 (TRIM31), and Casitas B-lineage lymphoma b (Cbl-b), which induce K48-linked ubiquitination of NLRP3, targeting it for proteasomal degradation. Membrane-associated RING-CH 7 (MARCH7) similarly promotes K48-linked ubiquitination leading to autophagic degradation, while RING finger protein (RNF125) induces K63-linked ubiquitination to modulate NLRP3 function. Ariadne homolog 2 (ARIH2) targets the nucleotide-binding domain (NBD) domain of NLRP3, inhibiting its activation, and tripartite motif-containing protein (TRIM65) employs dual K48 and K63-linked ubiquitination to suppress inflammasome assembly. Conversely, Pellino2 exemplifies a positive regulator, promoting NLRP3 inflammasome activation through K63-linked ubiquitination. Additionally, ubiquitin ligases influence other components critical for inflammasome function. TNF receptor-associated factor 3 (TRAF3) mediates K63 polyubiquitination of apoptosis-associated speck-like protein containing a CARD (ASC), facilitating its degradation, while E3 ligases regulate caspase-1 activation and DEAH-box helicase 33 (DHX33)-NLRP3 complex formation through specific ubiquitination events. Beyond direct inflammasome regulation, ubiquitin ligases impact broader innate immune signaling pathways, modulating pattern-recognition receptor responses and dendritic cell maturation. Furthermore, they intricately control NOD1/NOD2 signaling through K63-linked polyubiquitination of receptor-interacting protein 2 (RIP2), crucial for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, we explore how various pathogens, including bacteria, viruses, and parasites, have evolved sophisticated strategies to hijack the host ubiquitination machinery, manipulating NLRP3 inflammasome activation to evade immune responses. This comprehensive analysis provides insights into the molecular mechanisms underlying inflammasome regulation and their implications for inflammatory diseases, offering potential avenues for therapeutic interventions targeting the NLRP3 inflammasome. In conclusion, ubiquitin ligases emerge as key regulators of NLRP3 inflammasome activation, exhibiting a complex array of functions that finely tune immune responses. Understanding these regulatory mechanisms not only sheds light on fundamental aspects of inflammation but also offers potential therapeu","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"25970"},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of Macrophage-Mediated Inflammatory Response in Ocular Inflammatory Complications.","authors":"Sara McMahon, Tori Spector, Kota V Ramana","doi":"10.31083/FBL26698","DOIUrl":"https://doi.org/10.31083/FBL26698","url":null,"abstract":"<p><p>Immune cells such as macrophages play a significant role in ocular inflammation by activating or inhibiting several cellular pathways. Systemic infections and autoimmune diseases could activate macrophages by releasing various pro-inflammatory cytokines, chemokines, and growth factors, which reach the eyes through the blood-retina barrier and cause immune and inflammatory responses. In addition, environmental pollutants, allergens, and eye injuries could also activate macrophages and cause an inflammatory response. Further, the inflammatory response generated by the macrophages could recruit additional immune cells and enhance the inflammatory response. The inflammatory response leads to ocular tissue damage and dysfunction and affects vision. Macrophages are generally implicated in the clearance of pathogens and debris, generate reactive oxygen species, and initiate immune response. However, uncontrolled immune and inflammatory responses could damage the ocular tissues, leading to various ocular inflammatory complications such as uveitis, scleritis, diabetic retinopathy, and retinitis. Recent studies describe the role of individual cytokines in the mediation of specific ocular inflammatory diseases. In this article, we discussed the potential impact of macrophages and their mediated inflammatory response on the development of various ocular inflammatory diseases and possible treatment strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26698"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}