Frontiers in bioscience (Landmark edition)最新文献

{"title":"High-Intensity Interval Training Decreases Circulating HMGB1 in Individuals with Insulin Resistance: Plasma Lipidomics Correlate with Associated Cardiometabolic Benefits.","authors":"Gabriela Martinez Bravo, Prabu Paramasivam, Gabriella F Bellissimo, Quiteria Jacquez, Huayu Zheng, Fabiano Amorim, Lara Kovell, Roberto Ivan Mota Alvidrez","doi":"10.31083/FBL31396","DOIUrl":"10.31083/FBL31396","url":null,"abstract":"<p><strong>Background: </strong>Bodyweight high-intensity interval training (BW-HIIT) is an effective, time-efficient exercise method that reduces cardiovascular risk factors and improves muscle endurance without requiring external equipment. High mobility group box 1 (HMGB1) is a proinflammatory protein involved in insulin resistance. Previous studies revealed that <i>HMGB1</i> knockout mice show improved insulin sensitivity and hyperglycemia. This study investigates whether BW-HIIT exercise can reduce proinflammatory markers, such as HMGB1, in individuals with insulin resistance.</p><p><strong>Methods: </strong>In total, 14 adults (2 male/12 female) aged 18 to 55 were subject to six weeks of BW-HIIT. Additionally, 10-week-old mice were subject to exercise conditioning (5 mice per group (all male)) for 4 weeks of treadmill exercise or sedentary. Human and mouse pre- and post-exercise serum/plasma samples were analyzed for lipidomics, hormonal, and cytokine multiplex assays. Cardiometabolic parameters were also performed on human subjects.</p><p><strong>Results: </strong>Post-exercise decreased systolic blood pressure (SBP), cholesterol, triglycerides, high-density lipoprotein (HDL), and cholesterol/HDL ratio in human patients with insulin resistance. Meanwhile, hormones such as amylin, glucagon, and insulin all increased post-BW-HIIT or treadmill exercise in both human and mouse models. Moreover, circulating HMBG1 levels were reduced in insulin-resistant individuals and mice after exercise. Furthermore, treadmill exercise by the animal model increased anti-inflammatory cytokines, including interleukin (IL)-10, IL-12p40, and IL-12p70, and reduced proinflammatory cytokines: eotaxin, IL-2, and macrophage inflammatory protein (MIP)-2 or CXCL2.</p><p><strong>Conclusions: </strong>Six weeks of BW-HIIT exercise can improve cardiometabolic health, anti-inflammatory markers, hormones, and insulin sensitivity in human and mouse models undergoing exercise. Changes in circulating HMBG1 levels following BW-HIIT exercise make HMGB1 a suitable marker for cardiometabolic disease, potentiating its role beyond an alarmin. Further studies are needed to confirm these effects and to elucidate the underlying physiological mechanisms.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"31396"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733338","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":"Plasma Lipidomics, Gut Microbiota Profile, and Phenotype of Adipose Tissue in an <i>ApoE</i>^-/- Mouse Model of Plaque Instability.","authors":"Guanlin Yang, Xin Tan, Qiong Zhai, Yuewu Wang, Xuan Zhang, Pengwei Zhao, Fangyuan Liang, Jingkun Lu, LiLi Bao","doi":"10.31083/FBL27236","DOIUrl":"10.31083/FBL27236","url":null,"abstract":"<p><strong>Background: </strong>An appropriate animal model that can simulate the pathological process of atherosclerosis is urgently needed to improve treatment strategies. This study aimed to develop a new atherosclerosis model using <i>ApoE</i>^-/- mice and to characterize lipidomics, gut microbiota profiles, and phenotypic alterations in adipose tissue using this model.</p><p><strong>Methods: </strong>After a 14- or 18-week high-fat diet (HFD), male <i>ApoE</i>^-/- mice were randomly divided into four groups and treated separately with or without short-term and strong co-stimulation, including ice water bath and intraperitoneal injection of lipopolysaccharide and phenylephrine. As a control group, C57BL/6 mice were fed with conventional chow. The serum lipid levels, aortic arch pathology, adipose tissue phenotypic changes, plasma lipidomics, and <i>16S rDNA</i> gene sequencing of colon feces were investigated.</p><p><strong>Results: </strong>The serum lipid levels were significantly lowered following extended HFD feeding for four weeks. However, co-stimulation increased serum interleukin (IL)-1β levels but did not affect serum lipid profiles. Co-stimulation revealed typical vulnerable atherosclerotic plaque characteristics and defective adipose hypertrophy associated with peroxisome proliferator-activated receptor γ (PPARγ) regulation in adipose tissue and a reduction in mitochondrial uncoupling protein 1 (UCP1) within brown adipose tissue. Plasma lipidomic analysis showed that sphingomyelin (SM), ceramide (Cer), and monohexosylceramide (HexCer) levels in plasma were significantly elevated by HFD feeding, whereas co-stimulation further elevated HexCer levels. Additionally, glycerophosphocholines (16:0/16:0, 18:2/20:4, 18:1/18:1) and HexCer (C12:1, C16:0), Cer (d18:1/16:0), and SM (C16:0) were the most sensitive to co-stimulation. Combined co-stimulation and HFD-fed increased the abundance of <i>Firmicutes</i>, the abundance of <i>f_Erysipelotrichaceae</i>, and the <i>Firmicutes/Bacteroidota</i> ratio but decreased the abundance of microflora promoting bile acid metabolism and short-chain fatty acids (SCFAs) in mouse feces. The results were consistent with the findings of epidemiologic atherosclerotic cardiovascular disease studies.</p><p><strong>Conclusions: </strong>This study established an <i>ApoE</i>^-/- mouse atherosclerotic vulnerable plaque model using a multi-index evaluation method. Adipogenic disorders, dysregulation of lipid metabolism at the molecular level, and increasing harmful gut microbiota are significant risk factors for vulnerable plaques, with sphingolipid metabolism receiving the most attention.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"27236"},"PeriodicalIF":3.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732603","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":"Monitoring Autophagy in Human Aging: Key Cell Models and Insights.","authors":"Tatiana M Moreno, Jose L Nieto-Torres, Caroline Kumsta","doi":"10.31083/FBL27091","DOIUrl":"10.31083/FBL27091","url":null,"abstract":"<p><p>Autophagy, a key cellular degradation and recycling pathway, is critical for maintaining cellular homeostasis and responding to metabolic and environmental stress. Evidence for age-related autophagic dysfunction and its implications in chronic age-related diseases including neurodegeneration is accumulating. However, as a complex, multi-step process, autophagy can be challenging to measure, particularly in humans and human aging- and disease-relevant models. This review describes the links between macroautophagy, aging, and chronic age-related diseases. We present three novel human cell models, peripheral blood mononuclear cells (PBMCs), primary dermal fibroblasts (PDFs), and induced neurons (iNs), which serve as essential tools for studying autophagy flux and assessing its potential as a biomarker for aging. Unlike traditional models, these cell models retain age- and disease-associated molecular signatures, enhancing their relevance for human studies. The development of robust tools and methodologies for measuring autophagy flux in human cell models holds promise for advancing our understanding of autophagy's role in aging and age-related diseases, ultimately facilitating the discovery of therapies to enhance health outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"27091"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allergy Treatment: A Comprehensive Review of Nanoparticle-based Allergen Immunotherapy.","authors":"Mabrouk A Abo-Zaid, Reem M Elsapagh, Nourhan S Sultan, Wedad Mawkili, Maysa M Hegazy, Ahmed H Ismail","doi":"10.31083/FBL26550","DOIUrl":"10.31083/FBL26550","url":null,"abstract":"<p><p>Allergic disorders rising in prevalence globally, affecting a substantial proportion of individuals in industrialized nations. The imbalance in the immune system, characterized by elevated allergen-specific T helper 2 (Th2) cells and immunoglobulin E (IgE) antibodies, is a key factor in allergy development. Allergen-specific immunotherapy (AIT) is the only treatment capable of alleviating allergic symptoms, preventing new sensitizations, and reducing asthma risk in allergic rhinitis patients. Traditional AIT, however, faces challenges such as frequent administration, adverse effects, and inconsistent patient outcomes. Nanoparticle-based approaches have emerged as a promising strategy to enhance AIT. This review explores the utilization of nanoparticles in AIT, highlighting their ability to interact with the immune system and improve therapeutic outcomes. Various types of nanoparticles, including polyesters, polysaccharide polymers, liposomes, protamine-based nanoparticles (NPs), and polyanhydrides, have been employed as adjuvants or carriers to enhance AIT's efficacy and safety. Nanoparticles offer advantages such as allergen protection, improved immune response modulation, targeted cell delivery, and reduced side effects. This review provides an overview of the current landscape of nanoparticle-based allergen immunotherapy, discussing its potential to revolutionize allergy treatment compared to traditional immunotherapy.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26550"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733302","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":"Mast Cells and Microbiome in Health and Disease.","authors":"Vincenzo Papa, Federica Li Pomi, Mario Di Gioacchino, Rocco Mangifesta, Francesco Borgia, Sebastiano Gangemi","doi":"10.31083/FBL26283","DOIUrl":"10.31083/FBL26283","url":null,"abstract":"<p><p>Inter-kingdom communication between human microbiota and mast cells (MCs), as sentinels of innate immunity, is crucial in determining health and disease. This complex signaling hub involves micro-organisms and, more importantly, their metabolic products. Gut microbiota is the host's largest symbiotic ecosystem and, under physiological conditions, it plays a vital role in mediating MCs tolerogenic priming, thus ensuring immune homeostasis across organs. Conversely, intestinal dysbiosis of various etiologies promotes MC-oriented inflammation along major body axes, including gut-skin, gut-lung, gut-liver, and gut-brain. This review of international scientific literature provides a comprehensive overview of the cross-talk under investigation. This process is a key biological event involved in disease development across clinical fields, with significant prognostic and therapeutic implications for future research.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 3","pages":"26283"},"PeriodicalIF":3.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733430","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":"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":"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":"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":"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":"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":"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}