Frontiers in bioscience (Landmark edition)最新文献

{"title":"A Novel Liver-Specific Pseudogene Biomarker, BMS1P8, for Diagnosis and Prognosis in Hepatocellular Carcinoma.","authors":"Hyung Seok Kim, Ji Yi Choi, Geum Ok Baek, Moon Gyeong Yoon, Se Ha Jang, Ji Eun Han, Soon Sun Kim, Jae Youn Cheong, Jee-Yeong Jeong, Jung Woo Eun","doi":"10.31083/FBL41684","DOIUrl":"https://doi.org/10.31083/FBL41684","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Despite advances in therapeutic approaches, the lack of effective biomarkers continues to limit early detection and prognostic evaluation. Pseudogenes, once considered nonfunctional, have emerged as regulators of biological processes in tumors and as potential biomarkers. This study aimed to identify and validate BMS1 Pseudogene 8 (<i>BMS1P8</i>) as a liver-specific, clinically relevant diagnostic and prognostic biomarker in HCC.</p><p><strong>Methods: </strong>A comprehensive survey of pseudogene expression across different stages of liver disease was performed and validated using clinical HCC samples. Correlation, enrichment, and competing endogenous RNA (ceRNA) analyses integrating matched microRNA (miRNA)-seq and mRNA-seq were used to explore the functional networks surrounding <i>BMS1P8</i>. Public RNA-seq datasets (GSE114564, The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA_LIHC)) were used to delineate differentially expressed pseudogenes, and 98 paired tumor and non-tumor tissues were assessed using quantitative reverse transcription polymerase chain reaction. Diagnostic and prognostic performances were evaluated using receiver operating characteristic curves and Kaplan-Meier statistics.</p><p><strong>Results: </strong><i>BMS1P8</i> was markedly upregulated in HCC and was overexpressed in 25 other cancer types. Receiver operating characteristics analysis yielded an area under the curve of 0.81, underscoring the diagnostic utility. High <i>BMS1P8</i> expression and enrichment of cell cycle pathways were associated with poor survival. ceRNA screening revealed an inverse <i>BMS1P8</i>-miR-30c-2-3p correlation and concordant NME/NM23 nucleoside diphosphate kinase 6 (<i>NME6</i>) upregulation, with the <i>BMS1P8</i>/miR-30c-2-3p/<i>NME6</i> triad further stratifying patient outcomes.</p><p><strong>Conclusion: </strong>Our findings highlight <i>BMS1P8</i> as a novel liver-specific biomarker with substantial diagnostic and prognostic value in HCC. Its diagnostic utility suggests its potential application in early detection and personalized treatment strategies, contributing to improved patient outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"41684"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790907","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":"Light Hygiene for Circadian Health: A Molecular Perspective.","authors":"Denis Gubin, Oliver Stefani, Germaine Cornelissen","doi":"10.31083/FBL39097","DOIUrl":"https://doi.org/10.31083/FBL39097","url":null,"abstract":"<p><p>In discussing the interplay between light exposure/blue light exposure (LE/BLE) and circadian health, we emphasize the role of light hygiene and its effects on maintaining sleep, mood, and metabolic health, among other physiological processes. We define compromised circadian light hygiene as low dynamic range and/or irregular 24-hour patterns of LE. Poor light hygiene interferes with circadian entrainment and weakens circadian robustness alignment, thereby increasing health hazards. We provide an overview of the complex molecular pathways underlying light perception and downstream signaling. Given that genetic polymorphisms influence key elements within these light signaling pathways, we propose that personalized light hygiene approaches be designed for populations affected by compromised circadian LE or at risk of light-induced circadian disruption.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39097"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790925","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":"Na⁺,-K⁺-ATPase Deficiency Exacerbates Cardiac Fibrosis via Promoting ERRα-Mediated Myocardial Cell Injury and Macrophage Activation Under Isoproterenol-Challenged Conditions.","authors":"Ting Lei, Tao Liu, Yutong Liu, Yingnan Zhai, Ruijia Wang, Xiaoyi Tan, Hongli Liu, Xiaofei Yan","doi":"10.31083/FBL40363","DOIUrl":"https://doi.org/10.31083/FBL40363","url":null,"abstract":"<p><strong>Background: </strong>Inflammation plays a pivotal role in the progression of tissue fibrosis. Our previous research demonstrated that Na⁺, K⁺-ATPase (NKA) α1 deficiency impairs mitochondrial function and accelerates isoproterenol (ISO)-induced cardiac remodeling. This study aims to investigate the interplay between inflammation and NKAα1 deficiency in ISO-induced cardiac fibrosis.</p><p><strong>Methods: </strong>Age-matched male wild-type (WT) and NKAα1^+/- mice received daily subcutaneous injections of ISO (30 mg/kg body weight) over 14 consecutive days. Comprehensive histopathological evaluation was performed to assess myocardial architecture and leukocyte infiltration profiles. Mitochondrial ultrastructure was analyzed using transmission electron microscopy. The molecular techniques of real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) were utilized to quantify fibrotic markers and inflammatory mediators. A cell co-culture model was established to investigate the interactions between different cell types.</p><p><strong>Results: </strong>NKAα1 haploinsufficiency exacerbated heart lesions and fibrosis, led to macrophage accumulation, and increased the expression of inflammatory factors in ISO-challenged hearts. Although NKAα1 deficiency did not directly activate macrophages or fibroblasts under ISO conditions, it significantly accelerated cardiomyocyte death in response to ISO insult. Paracrine crosstalk between damaged NKAα1^+/- cardiomyocytes, macrophages, and fibroblasts amplified macrophage activation, inflammatory cytokine release, and fibroblast differentiation. Estrogen-related receptor α (ERRα) was identified as a key mediator of NKAα1 haploinsufficiency-induced cardiomyocyte death and interleukin-18 (IL-18) release. Furthermore, treatment with an NKAα1 ⁸⁹⁷DVEDSYGQQWTYEQR⁹¹¹ (DR)-region antibody mitigated ISO-induced cardiac fibrosis and macrophage infiltration.</p><p><strong>Conclusion: </strong>This study provides evidence that NKAα1 deficiency exacerbates cardiac fibrosis by promoting ERRα-dependent cardiomyocyte death and by facilitating intercellular cross-talk between damaged NKAα1^+/- cardiomyocytes, macrophages, and fibroblasts. Based on these findings, we suggest that NKAα1 may be a potential regulator of cardiac fibrosis, and that its DR-region represents a potential therapeutic target.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"40363"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790928","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":"Membrane Proteins: New Insights into Structure, Metabolic Functions and Disease-Relevant Mutations.","authors":"Daniela Valeria Miniero","doi":"10.31083/FBL40081","DOIUrl":"https://doi.org/10.31083/FBL40081","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"40081"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790926","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":"Cold Stress Regulates Muscle Development and Promotes Muscle Fiber Transformation by Regulating Mib1/Notch Pathway.","authors":"Minxing Zheng, Jiahui Qi, Xuanjing Wang, Tingting Fu, Ziqi Chang, Tong Zhao, Yaqin Sun, Jiayin Lu, Yi Yan, Haidong Wang","doi":"10.31083/FBL40141","DOIUrl":"https://doi.org/10.31083/FBL40141","url":null,"abstract":"<p><strong>Background: </strong>In mammals, skeletal muscle typically constitutes approximately 55% of body weight. The thermogenesis of skeletal muscle increases with increased cold stress, and skeletal muscle maintains the animal's body temperature through the heat generated by shivering. However, less attention has been paid to investigating the impact of cold stress on the fiber type makeup of skeletal muscle, especially the gastrocnemius. Consequently, this research explored how cold stress regulates muscle development and fiber type composition.</p><p><strong>Methods: </strong>A cold stress model was established by subjecting mice to a 4 °C environment for 4 hours daily. This model was combined with an <i>in vitro</i> siRNA-mediated knockdown model for joint validation. The impact of cold stress on skeletal muscle development and myofiber type transformation was assessed using experimental techniques, including immunofluorescence and western blotting.</p><p><strong>Results: </strong>Following cold stress, the expression level of Myosin Heavy Chain 7 (<i>MYH7</i>) in the mouse gastrocnemius increased, while Myosin Heavy Chain 4 (<i>MYH4</i>) expression decreased. Concurrently, elevated expressions of Mindbomb-1 (<i>Mib1</i>) and the myogenic differentiation (MyoD) were observed. Subsequent knockdown of <i>Mib1</i> in C2C12 cells resulted in increased <i>MYH4</i> expression and decreased <i>MYH7</i> expression.</p><p><strong>Conclusion: </strong>Cold stress induces skeletal muscle fibers to shift from fast-twitch to slow-twitch through the Mib1/Notch signaling pathway.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"40141"},"PeriodicalIF":3.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790916","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":"Potassium Clearance in Optic Nerve: A Multidomain Model.","authors":"Shanfeng Xiao, Huaxiong Huang, Robert Eisenberg, Zilong Song, Shixin Xu","doi":"10.31083/FBL39722","DOIUrl":"https://doi.org/10.31083/FBL39722","url":null,"abstract":"<p><strong>Background: </strong>Ion and water transport in the central nervous system (CNS) is governed by tightly coupled mechanisms involving electrodiffusion, osmotic pressure, and fluid convection. Disruptions to these processes are implicated in pathological conditions. Understanding the coordinated roles of glial cells and perivascular spaces in regulating ionic and fluid homeostasis is essential for interpreting neural function and dysfunction.</p><p><strong>Methods: </strong>We developed a multicompartment model of the optic nerve incorporating axons, glial cells, extracellular space (ECS), and three perivascular compartments (arterial, venous, and capillary-associated). The model integrates electrodiffusion of ions, osmotic water transport, and convection, while enforcing electroneutrality and compartmental volume conservation. Numerical simulations were performed using a finite volume method under axisymmetric geometry, and parameter sensitivity was explored through variations in glial membrane conductance, connexin permeability, and aquaporin-4 (AQP4) expression.</p><p><strong>Results: </strong>The simulations reveal that potassium released from axons during stimulation is cleared via glial uptake and redistributed through electric drift within glial syncytia. The perivascular pathway provides a secondary route for potassium and water clearance. Decreased glial conductance leads to abnormal firing in unstimulated axons, mimicking epileptiform activity, while reduced connexin coupling increases dependence on perivascular drainage. Changes in AQP4 expression had limited effect on ionic homeostasis in the current model.</p><p><strong>Conclusions: </strong>This model provides a biophysically consistent framework to study ionic-fluid coupling in CNS microcirculation. It demonstrates how glial and perivascular compartments cooperate to maintain extracellular potassium balance. The findings offer insight into the mechanisms underlying pathological K⁺ accumulation and suggest potential therapeutic targets involving glial modulation and perivascular enhancement. The framework is extensible to other brain regions and conditions involving impaired clearance or excitability.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39722"},"PeriodicalIF":3.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790930","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":"Innate Priming and Tumor-Associated Macrophage Reprogramming: A Commentary on Emerging Immunotherapeutic Strategies.","authors":"Sahar Balkhi, Anna Di Spirito, Lorenzo Mortara","doi":"10.31083/FBL41097","DOIUrl":"https://doi.org/10.31083/FBL41097","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"41097"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790922","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":"Dual Role of Quercetin in Promoting Early Wound Healing via Inhibiting Inflammatory Factors and Attenuating Scar Formation by Suppressing Myofibroblast Differentiation.","authors":"Dan Wu, Mengyuan Jiang, Jing Zhang","doi":"10.31083/FBL40077","DOIUrl":"https://doi.org/10.31083/FBL40077","url":null,"abstract":"<p><strong>Background: </strong>Quercetin, a naturally occurring flavonoid, possesses anti-inflammatory properties and has emerged as a potential modulator of tissue repair. Impaired wound healing and pathological scarring are often driven by excessive inflammation and dysregulated myofibroblast differentiation. Current therapeutic approaches, however, frequently fall short in simultaneously addressing these intertwined challenges. This study investigates whether quercetin can provide a bifunctional therapeutic advantage by promoting early wound closure through inflammation resolution and suppressing scar formation via the inhibition of myofibroblast differentiation.</p><p><strong>Methods: </strong>A murine excisional wound model was employed to evaluate quercetin's effects <i>in vivo</i>. Mice (C57BL/6, <i>n</i> = 8/group) received daily topical applications of 1% quercetin. Wound closure kinetics were meticulously quantified using planimetry. To assess molecular and cellular changes, protein levels (CASPASE-1, interleukin-1 beta (IL-1β), alpha-smooth muscle actin (α-SMA)) and collagen III/I ratios were determined through multiplex qPCR, RNA sequencing, western blot analysis, and histomorphometry. For <i>in vitro</i> investigations, human dermal BJ fibroblasts were treated with transforming growth factor beta 1 (TGF-β1) (10 ng/mL) ± quercetin (5-50 μM) to assess myofibroblast differentiation markers (α-SMA, collagen I) via immunofluorescence, western blot, and qPCR.</p><p><strong>Results: </strong>Quercetin significantly accelerated wound closure <i>in vivo</i>. The acceleration was accompanied by a reduction in the expression of IL-1β and CASPASE-1. RNA sequencing data revealed that quercetin's anti-inflammatory effects in early wound healing involve the modulation of inflammasome complexes, including NLRP3, as well as inflammasome-mediated signaling pathways. Furthermore, treated wounds exhibited increased collagen III/I ratios relative to control groups (<i>p</i> < 0.05), indicative of a more regenerative matrix remodeling process. <i>In vitro</i>, experiments demonstrated that quercetin suppressed TGF-β1-induced myofibroblast differentiation, evidenced by decreased α-SMA expression (<i>p</i> < 0.05) and reduced collagen I synthesis. Notably, quercetin exhibited cell type-specific effects: while suppressing BJ fibroblast migration (scratch assay), it enhanced keratinocyte proliferation. This unique duality prevents aberrant myofibroblast recruitment without compromising essential epithelial coverage-a critical balance for minimizing scar formation.</p><p><strong>Conclusions: </strong>Quercetin exhibits a compelling dual therapeutic role in wound healing: resolving inflammation to expedite early wound healing and inhibiting TGF-β-driven myofibroblast differentiation to attenuate scarring. By harmonizing these actions, quercetin addresses both phases of repair, positioning it as a promising candidate for scar-free wound therapy. Further efforts","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"40077"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790919","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":"Brain Organoids: From Lab Bench to Neural Repair.","authors":"Paschalis Theotokis, George Agiotis, Maria Eleni Manthou","doi":"10.31083/FBL39407","DOIUrl":"https://doi.org/10.31083/FBL39407","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39407"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790913","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":"Iron Fist in a Velvet Glove: Class IV Ferroptosis Inducers as a Novel Strategy to Target Ovarian Cancer.","authors":"Lavinia Petriaggi, Emanuele Giorgio, Giuseppe Natali, Cristiana Galeano, Simão Rodrigues Furtado, Concetta Maria Faniello, Francesco Saverio Costanzo, Flavia Biamonte, Anna Martina Battaglia","doi":"10.31083/FBL39675","DOIUrl":"https://doi.org/10.31083/FBL39675","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy characterized by frequent late-stage diagnosis, high rates of chemoresistance, and poor long-term survival. Emerging evidence underscores the central role of iron metabolism dysregulation in EOC pathogenesis, progression, and treatment resistance. Ovarian cancer cells and cancer stem cells exhibit an \"iron-addicted\" phenotype, characterized by increased iron uptake, reduced export, and enhanced storage, which sustains proliferative signaling, redox imbalance, and metastatic potential. Recent advances have illuminated ferroptosis, a regulated form of iron-dependent cell death driven by lipid peroxidation, as a promising therapeutic target for overcoming resistance to platinum-based chemotherapy. This review provides a comprehensive synthesis of the mechanisms governing iron metabolism and ferroptosis in EOC, with a particular focus on Class IV ferroptosis inducers (FINs). These agents act by disrupting iron homeostasis and promoting labile iron pool accumulation, thereby triggering oxidative stress and ferroptotic death. Preclinical studies demonstrate that Class IV FINs, including iron nitroprusside, superparamagnetic iron oxide nanoparticles, ferric ammonium citrate, and Ferlixit, exhibit potent antitumor activity in EOC models, particularly in chemoresistant and stem-like tumor subpopulations. Furthermore, Class IV FINs show synergistic effects when combined with other ferroptosis modulators or immunotherapeutic agents. Despite their promise, clinical translation remains limited by challenges in bioavailability, delivery specificity, and potential systemic toxicity. Ongoing efforts in nanotechnology, biomarker discovery, and tumor stratification offer new avenues for refining ferroptosis-based interventions. Ultimately, this review highlights Class IV FINs as a mechanistically distinct and clinically actionable strategy to target metabolic vulnerabilities in EOC, with the potential to reshape therapeutic paradigms and improve patient outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"39675"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790923","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}