Frontiers in bioscience (Landmark edition)最新文献

{"title":"The Role of Gut Microbiota in Osteoporosis Triggered by High-Fat Diets: Mechanisms and Targeted Therapeutic Strategies.","authors":"Xinping Wang, Lijie Lin, Yuanzhang Xiao, Renwei Liu, Yingchao Cai, Wuyang Liu, Kai Zhao","doi":"10.31083/FBL46209","DOIUrl":"https://doi.org/10.31083/FBL46209","url":null,"abstract":"<p><p>Overnutrition, and specifically a high-fat diet (HFD) in which more than 30% of energy intake is derived from fat, has been unequivocally identified as a modifiable risk factor for several major diseases including osteoporosis, cardiovascular disorders, diabetes, and metabolic syndrome. The continued rise in prevalence of osteoporosis, particularly among younger populations, along with widespread adoption of HFD, has made the underlying mechanisms and preventative strategies related to HFD-induced osteoporosis a primary focus in the field of bone metabolism research. Early studies suggested that HFD-mediated weight gain might confer protective effects on skeletal health. However, emerging evidence reveals that HFD disrupts bone metabolic homeostasis and accelerates the progression of osteoporosis through multiple pathways, including pathological expansion of adipose tissue, systemic chronic inflammation, and gut microbial dysbiosis. The gut microbiota (GM) is a crucial mediator of dietary fat absorption and is increasingly recognized as a pivotal factor in the pathogenesis of HFD-associated osteoporosis. HFD-induced alterations in gut microbial composition and metabolic function compromise intestinal barrier integrity, triggering chronic systemic inflammation and metabolic disturbances that collectively exacerbate bone loss and promote osteoporosis. Targeted microbiota interventions have shown promise in ameliorating bone deterioration, paving the way for innovative therapeutic approaches against HFD-related osteoporosis. This review systematically examines the pathways through which HFD induces osteoporosis via modulation of GM, and evaluates emerging microbiota-focused treatment strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"46209"},"PeriodicalIF":3.1,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623032","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":"Integrative Bioinformatics and Experimental Validation Reveal that METTL9 Drives Lung Adenocarcinoma Progression via TGF-β/Smad-Mediated EMT Activation.","authors":"Chen Gong, Yuyan Chen, Yuchen Xie, Yuling Liu, La Jiang, Haoyuan Jiang, Zhijun Chen, Bin Yuan, Xueqin Zhang","doi":"10.31083/FBL49673","DOIUrl":"https://doi.org/10.31083/FBL49673","url":null,"abstract":"<p><strong>Background: </strong>Methyltransferase-like 9 (METTL9) has been implicated in tumor progression, yet its clinical significance, functional roles, and immunoregulatory functions in lung adenocarcinoma (LUAD) remain unclear. This study aimed to integrate multi-omics datasets and experimental evidence to systematically evaluate the expression profile, prognostic value, molecular mechanisms, and tumor microenvironment (TME)-related functions of METTL9 in LUAD.</p><p><strong>Methods: </strong>Transcriptome and clinical data for LUAD and METTL9 protein expression were obtained from public databases. Survival analysis was performed using Kaplan-Meier analysis and Cox proportional hazards models. METTL9-related differentially expressed genes (DEGs) were screened, followed by functional annotation and pathway enrichment analysis. A protein-protein interaction (PPI) network associated with METTL9 was constructed using STRING. METTL9 gene mutations and promoter methylation levels were analyzed via cBioPortal and UALCAN. Immune infiltration was evaluated through gene set variation analysis (GSVA) and the TIMER platform. The role of METTL9 depletion in regulating transforming growth factor-β (TGF-β)/Smad signaling, epithelial-mesenchymal transition (EMT), as well as the behavior of A549 and H1975 cells was investigated.</p><p><strong>Results: </strong>METTL9 was markedly elevated in LUAD, which was confirmed in external datasets and immunohistochemistry. Increased METTL9 expression showed a strong association with advanced TNM stage, unfavorable clinicopathological parameters, and poor survival outcomes in univariate analysis. Receiver operating characteristic (ROC) analysis indicated that METTL9 showed moderate diagnostic utility for LUAD, with an Area Under the Curve (AUC) of 0.704 (95% Confidence Interval [CI]: 0.650-0.758) in the The Cancer Genome Atlas (TCGA) dataset and 0.815 (95% CI: 0.758-0.872) in the GSE31210 dataset. Moreover, high METTL9 expression was significantly correlated with poor survival outcomes (Hazard Ratio [HR] = 1.349, 95% CI: 1.010-1.802, <i>p</i> = 0.043). METTL9 interacted with multiple oncogenic proteins in the PPI network and showed significant correlations with cuproptosis-related genes. Immune infiltration analysis further demonstrated that METTL9 expression showed significantly associated with immune cell infiltration and the tumor immune microenvironment in LUAD. METTL9 knockdown suppressed LUAD cell proliferation, migration, invasion, and EMT, while promoting apoptosis and reducing the expression of B-cell lymphoma 2 (Bcl-2), phosphorylated Smad2 (p-smad2), and phosphorylated Smad3 (p-smad3).</p><p><strong>Conclusion: </strong>METTL9 is upregulated in LUAD and correlates with an unfavorable prognosis. Our results indicate that METTL9 may contribute to LUAD progression and EMT, potentially in relation to the TGF-β/Smad signaling pathway.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"49673"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622934","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":"<i>Lachnospiraceae</i> and Its Metabolite Malate Act in Concert to Repair Gut Microbiota Imbalance and Block Colorectal Cancer Progression.","authors":"Zejun Fang, Yanyan Hu, Minjing Zhu, Hengming Mei, Chaoju Gong, Jiaoe Chen","doi":"10.31083/FBL52075","DOIUrl":"https://doi.org/10.31083/FBL52075","url":null,"abstract":"<p><strong>Background: </strong>Gut microbiota dysbiosis is a crucial driver of the initiation and progression of colorectal cancer (CRC), where functional gut microbes and their metabolites play key roles in the microecological regulation of CRC. Currently, the association between <i>Lachnospiraceae</i> and CRC progression, as well as the underlying mechanisms, remains incompletely understood and warrants further investigation.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed to explore the co-pathway association between gut microbiota and metabolites in CRC patient samples. <i>In vivo</i> animal models were established to assess the regulatory effects of <i>Lachnospiraceae</i> on CRC tumorigenesis and gut microbiota homeostasis. The anti-CRC activities of <i>Lachnospiraceae</i> and its metabolite malate were investigated using <i>in vitro</i> experiments that measured cell viability, proliferation, apoptosis, and colony formation. Western blotting was performed to detect the expression levels of key proteins in the Wingless/Integrated (Wnt)/β-catenin signaling pathway.</p><p><strong>Results: </strong>Bioinformatics analysis revealed that malate was significantly downregulated in CRC patients, accompanied by gut microbiota dysbiosis driven predominantly by short-chain fatty acid (SCFA)-related Firmicutes such as <i>Lachnospiraceae</i> and <i>Ruminococcaceae</i>. <i>In vivo</i>, <i>Lachnospiraceae</i> restored gut microbiota homeostasis, reduced tumor number, and decreased tumor load. <i>In vitro</i>, <i>Lachnospiraceae</i> suppressed colorectal tumorigenesis and increased colonic D-malate levels.</p><p><strong>Conclusion: </strong><i>Lachnospiraceae</i> bacterium biologics abstracts accession-2278 (BAA-2278) is associated with anti-CRC effects in preclinical models, potentially mediated through regulation of gut microbiota homeostasis and inhibition of Wnt/β-catenin signaling via its metabolite malate.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"52075"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622524","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":"Transcriptomic and Single-Cell Analyses Reveal a Prognostic Mitochondria- and Immunity-Related Risk Signature in Osteosarcoma.","authors":"Jiangbo Ai, Zhidong Peng, Peichuan Xu, Jinghong Yuan, Xinxin Miao, Guoyu Yang, Jiangminghao Zhao, Xigao Cheng","doi":"10.31083/FBL51093","DOIUrl":"https://doi.org/10.31083/FBL51093","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;While mitochondrial dysfunction and immune cell dysregulation have been established as important contributors to the pathogenesis of osteosarcoma (OS), the prognostic value of mitochondria-related genes (MRGs) and immune-related genes (IRGs) in OS remains poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were obtained from public databases. Differentially expressed genes (DEGs) and key module genes were identified viadifferential expression analysis and weighted gene co-expression network analysis, respectively. Candidate genes of interest were identified by intersecting key module genes, DEGs, MRGs, and IRGs. Then, candidate genes were screened using regression analysis and proportional hazards assumption testing to identify prognostic genes. A risk model was then constructed in the TARGET-OS dataset and validated in GSE16091. Independent prognostic, immune infiltration, and gene expression analyses were conducted. In addition, single-cell analysis was performed to identify key cell populations, and pseudotime analysis as well as cell communication network construction were carried out. Finally, the expression patterns of selected prognostic genes were additionally validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the functional role of protein kinase Cα (&lt;i&gt;PRKCA&lt;/i&gt;) in osteosarcoma cell proliferation, migration, and invasion was evaluated &lt;i&gt;in vitro&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Glutathione S-transferase Pi-1 (&lt;i&gt;GSTP1&lt;/i&gt;), catalase (&lt;i&gt;CAT&lt;/i&gt;), &lt;i&gt;TNFSF10&lt;/i&gt;, and &lt;i&gt;PRKCA&lt;/i&gt; were identified as mitochondria- and immunity-related prognostic genes in OS and were used to construct a risk model. The risk model was able to effectively predict the survival of patients with OS. A nomogram based on the identified prognostic genes additionally exhibited excellent performance when predicting OS patient survival. Significant differences in the abundance of 14 immune cell types and 8 immune checkpoint molecules were noted between the high-risk and low-risk groups. Single-cell analyses were then conducted to annotate 10 cell types, and M1 macrophages were identified as a potentially relevant cell population in the OS microenvironment. During M1 macrophage differentiation, initial reductions in &lt;i&gt;CAT&lt;/i&gt; and &lt;i&gt;PRKCA&lt;/i&gt; expression were noted, followed by subsequent increases and final decreases. In contrast, the expression of &lt;i&gt;GSTP1&lt;/i&gt; and &lt;i&gt;TNFSF10&lt;/i&gt; in these cells first rose and then declined. Furthermore, &lt;i&gt;PRKCA&lt;/i&gt; was selected for further &lt;i&gt;in vitro&lt;/i&gt; analyses, which revealed that it can enhance the invasion, migration, and proliferation of OS cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study identified &lt;i&gt;GSTP1&lt;/i&gt;, &lt;i&gt;CAT&lt;/i&gt;, &lt;i&gt;TNFSF10&lt;/i&gt;, and &lt;i&gt;PRKCA&lt;/i&gt; as prognostic genes associated with mitochondrial and immune function in OS, with &lt;i&gt;in vitro&lt;/i&gt; evidence providing direct support for the potential functional role of &lt;i&gt;PRKCA&lt;/i&gt; in OS p","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51093"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622052","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":"Neutrophil Extracellular Traps in Aortic and Cerebrovascular Diseases: Biomarkers, Immunomodulation, and Device-Related Strategies.","authors":"Rasit Dinc, Nurittin Ardic","doi":"10.31083/FBL48293","DOIUrl":"https://doi.org/10.31083/FBL48293","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) have emerged as important mediators at the interface of innate immunity, thrombosis, and vascular remodeling. Aortic aneurysms and cerebrovascular diseases are now recognized as prototypical NET-driven conditions in which dysregulated immunothrombosis accelerates wall degeneration, promotes thrombus formation, and exacerbates tissue damage. This narrative review synthesizes current evidence on NET biology in the context of abdominal and thoracic aortic aneurysms, acute aortic syndromes, ischemic stroke, and intracerebral hemorrhage. First, we summarize the molecular mechanisms of NET formation, regulation, and clearance, outlining how NETs shape the immunothrombotic niche in aneurysm thrombi and the cerebral vasculature. Following this, experimental and clinical data on circulating and tissue NET markers are examined in relation to disease presence, lesion instability, hematoma expansion, and functional outcome, thereby highlighting their potential as diagnostic and prognostic biomarkers. Thereafter, pharmacological strategies that either inhibit NET formation or enhance NET degradation are discussed. We then examine how multilayered flow modulators, biodegradable scaffolds, and bioinspired stent coatings can modulate NET responses at the blood-device interface. Finally, we explore the emerging roles of multi-omics profiling, molecular imaging, artificial intelligence (AI)-based analyses in integrating NET-related signals into personalized risk prediction, device selection, and treatment monitoring. Collectively, these findings position NETs as central targets for biomarker development, immunomodulatory therapy, and immunobioengineered vascular devices. NET-informed precision management of aortic and cerebrovascular diseases is therefore a key area for further research.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"48293"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622954","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":"CRABP2 Promotes Lung Adenocarcinoma Through Retinoic Acid Pathway-Mediated NF-κB Activation.","authors":"XiRui Zhu, BiaoFeng Fan, Qing Lei, ChenJun Xin, XuanCheng Li, ZhongRui Ma, SiQi Xie, JianLiang Shang, ZuYang Li, Chao Liu, WeiWei Wang","doi":"10.31083/FBL51377","DOIUrl":"https://doi.org/10.31083/FBL51377","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a major cause of cancer-related mortality. Despite advances in targeted therapies, tumor heterogeneity and acquired resistance frequently undermine clinical outcomes. This study aimed to identify novel oncogenic drivers and underlying mechanisms in LUAD.</p><p><strong>Methods: </strong>We examined cellular retinoic acid-binding protein 2 (CRABP2) expression in human LUAD specimens and evaluated its functional role through <i>in vitro</i> assays (cell proliferation, migration, invasion, and apoptosis) and <i>in vivo</i> xenograft tumor growth. Mechanistic exploration involved RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and immunoblotting for the nuclear factor kappa B (NF-κB) signaling components, along with rescue experiments to dissect the pathway dependency.</p><p><strong>Results: </strong>CRABP2 was identified as a candidate oncogene in LUAD. Functional assays confirmed that CRABP2 promoted proliferation, migration, and invasion, suppressed apoptosis, and accelerated xenograft tumor growth. Mechanistically, CRABP2 potentiated retinoic acid (RA) signaling and activated the NF-κB pathway, as evidenced by enhanced inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) phosphorylation, subsequent NF-κB inhibitor alpha (IκBα) phosphorylation, and nuclear translocation of total and phosphorylated p65. Rescue experiments revealed that CRABP2‑induced NF-κB activation is RA-dependent and that this activation mediates the oncogenic effects of CRABP2.</p><p><strong>Conclusions: </strong>Our findings establish a CRABP2/RA/NF‑κB axis that drives LUAD progression, highlighting this pathway as a potential therapeutic target for intervention in LUAD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51377"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622825","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":"Region- and Cell-Specific Vulnerability to ROS After Global Brain Ischemia-Reperfusion Injury: Molecular and Cellular Mechanisms.","authors":"Bo Hyun Jung, Ki-Yeon Yoo","doi":"10.31083/FBL48324","DOIUrl":"https://doi.org/10.31083/FBL48324","url":null,"abstract":"<p><p>Global brain ischemia-reperfusion (I/R) injury manifests as selective neuronal vulnerability rather than uniform tissue damage. Specific neuroanatomical regions-most notably the hippocampal cornu ammonis 1 (CA1) subfield, striatum, and cerebellum-exhibit a heightened susceptibility to oxidative stress-induced degeneration. This review consolidates current understanding regarding the region- and cell-specific vulnerability to reactive oxygen species (ROS) following global I/R, highlighting the molecular and cellular determinants that drive this selectivity. We examine the spatial distribution of ROS-generating systems, including NADPH oxidases (NOX2/NOX4) and mitochondrial complexes, alongside the divergent expression of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. Inherent neuronal properties, such as elevated synaptic activity, calcium permeability, and rigorous metabolic demands, further exacerbate oxidative injury. Additionally, we evaluate how astrocyte-neuron interactions and regional variations in blood-brain barrier (BBB) integrity modulate the severity and progression of ROS-induced damage. The roles of astrocytic endfoot polarization, aquaporin-4 (AQP4) localization, and Kir4.1-mediated potassium buffering in post-ischemic outcomes are also discussed. Furthermore, this review surveys emerging antioxidant-based therapies-ranging from edaravone and melatonin to selenium nanoparticles and miRNA-based interventions-while addressing translational hurdles like narrow therapeutic windows and inter-individual variability. By synthesizing experimental and translational evidence, this work provides a comprehensive framework for understanding oxidative stress-related vulnerability in I/R injury. Ultimately, it underscores the necessity for precision antioxidant strategies tailored to brain-region specificity, pathophysiological timing, and patient-specific factors to improve clinical outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"48324"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622912","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":"Troxerutin Activity Against Oxidative Stress: A Potential Strategy for Corneal Damage Evaluated in a 3D Model of Human Corneal Epithelial Cells.","authors":"Rossella Basilotta, Alessia Filippone, Nicoletta Palermo, Giovanna Casili, Marika Lanza, Emanuela Esposito, Irene Paterniti","doi":"10.31083/FBL51862","DOIUrl":"https://doi.org/10.31083/FBL51862","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress and inflammation are closely associated with ocular surface disorders, including dry eye disease (DED), keratitis, and corneal erosion. These pathological processes contribute to an imbalance in tear composition and induce structural and functional alterations of the cornea. In this context, natural compounds with antioxidant and anti-inflammatory activities have emerged as promising strategies for preserving ocular health and mitigating the effects of corneal injuries. In the present study, we investigated the potential protective effects of troxerutin (TX), a naturally occurring flavonoid, in attenuating oxidative stress and promoting the restoration of corneal tissue architecture.</p><p><strong>Methods: </strong>To this end, an H₂O₂-induced oxidative stress model was established using human corneal epithelial cells (HCE) SkinEthic™ 3D tissues. Cells were pretreated with TX and, after 24 hours, stimulated with H₂O₂ for 10 minutes.</p><p><strong>Results: </strong>TX showed a protective effect against oxidative injury in the HCE 3D model and supported morphological recovery consistent with re-epithelialization through the upregulation of tight junction proteins zona occludens-1 (<i>ZO-1</i>) and <i>Occludin</i>. In addition, TX helped attenuate inflammatory responses by regulating interleukin-6 (<i>IL-6</i>), interleukin-8 (<i>IL-8</i>), matrix metallopeptidase 9 (<i>MMP-9</i>), and key adhesion molecules, including intercellular adhesion molecule-1 (<i>ICAM-1</i>) and <i>P-selectin</i>.</p><p><strong>Conclusions: </strong>Overall, these findings emphasize the potential of TX as a natural compound that may contribute to the prevention and management of corneal damage.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51862"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622018","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":"Viruses and Antiviral Responses of Nematodes.","authors":"Dustin T Howard, Vladimir Lažetić","doi":"10.31083/FBL51009","DOIUrl":"https://doi.org/10.31083/FBL51009","url":null,"abstract":"<p><p>Nematodes are ubiquitous metazoans that occupy diverse ecological niches, exposing them to a wide range of viruses and positioning them as both viral hosts and vectors. Free-living nematodes, particularly <i>Caenorhabditis elegans</i> and <i>Caenorhabditis briggsae</i>, provide powerful genetic models for studying antiviral immune mechanisms. Natural infections with noda-like viruses have revealed powerful antiviral defense strategies in <i>Caenorhabditis</i> species, including RNA interference, the Intracellular Pathogen Response, Signal Transducers and Activators of Transcription (STAT)-like transcriptional regulation, terminal RNA uridylation, and structural barriers to viral entry and egress. These mechanisms demonstrate robust antiviral mechanisms independent of canonical interferon signaling while relying on conserved principles of viral RNA recognition, signal amplification, and coordinated transcriptional responses. Beyond free-living species, parasitic nematodes harbor a diverse and largely unexplored virome. Plant-parasitic nematodes host multiple RNA viruses and act as vectors for economically and agriculturally important plant pathogens, while animal-parasitic nematodes carry persistent viral infections that may influence the immune responses and disease outcomes of their animal hosts. Evidence for functional antiviral RNA interference in parasitic nematodes suggests partial conservation of immune mechanisms, although functional data remain limited. Together, these findings define current knowledge of viral infections and antiviral responses in nematodes and emphasize the need for deeper mechanistic studies, particularly in parasitic species, where the molecular basis of viral recognition and immune defense remains poorly characterized.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"51009"},"PeriodicalIF":3.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622492","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":"Downregulation of <i>PHB1</i> due to Loss of VHL Protein Expression Promotes the Malignancy Progression of Kidney Renal Clear Cell Carcinoma.","authors":"Chenbin Cao, He Qi, Lu Xiang, Wenshuai Zhu, Yuxuan Shi, Xiaoli Ma, Yunshan Wang, Yanfei Jia, Yuanxin Xing","doi":"10.31083/FBL53057","DOIUrl":"https://doi.org/10.31083/FBL53057","url":null,"abstract":"<p><strong>Background: </strong>Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases. Although Prohibitin 1 (<i>PHB1</i>) has been implicated in tumorigenesis, its role in KIRC remains unclear. This study aimed to investigate the expression, function, and underlying mechanisms of <i>PHB1</i> in KIRC.</p><p><strong>Methods: </strong><i>PHB1</i> expression and clinical relevance were analyzed using the Cancer Genome Atlas database (TCGA), Gene Expression Omnibus database (GEO), and TIMER3.0 datasets. Single-cell RNA sequencing (scRNA-seq) data from 19 KIRC patients and normal kidney samples were used to assess cell-type-specific expression. Functional experiments, including CCK-8, EdU incorporation, colony formation, and Transwell assays, were performed to evaluate the effects of <i>PHB1</i> on cell proliferation, migration, and invasion. A xenograft model was used to evaluate the effects of <i>PHB1</i> in vivo. Western blotting and correlation analyses were conducted to assess the potential regulatory interplay between VHL, SKP2, PHB1, and p53.</p><p><strong>Results: </strong><i>PHB1</i> was significantly downregulated in KIRC tissues. Single-cell analysis showed reduced <i>PHB1</i> expression in tumor-derived epithelial cells, fibroblasts, endothelial cells, and immune cells. Lower <i>PHB1</i> levels were associated with poorer overall survival. <i>PHB1</i> overexpression inhibited proliferation and migration, whereas knockdown promoted these effects. <i>In vivo</i>, <i>PHB1</i> overexpression reduced tumor growth. Moreover, VHL knockout altered the protein levels of SKP2 and <i>PHB1</i>. Cellular manipulation of <i>PHB1</i> moderately altered endogenous p53 protein expression. Based on TCGA data analysis, <i>PHB1</i> expression showed a positive correlation with VHL and a negative correlation with SKP2.</p><p><strong>Conclusions: </strong>Collectively, <i>PHB1</i> acts as a potential tumor suppressor in KIRC. Its expression pattern is associated with the VHL-SKP2 signaling axis, and the tumor-suppressive effects of <i>PHB1</i> may be partially associated with the modulation of p53 expression. These findings suggest that <i>PHB1</i> has the potential to serve as a reliable biomarker and therapeutic candidate for KIRC treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 7","pages":"53057"},"PeriodicalIF":3.1,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622779","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}