Frontiers in bioscience (Landmark edition)最新文献

{"title":"PIAS2 Overexpression Attenuates Erastin-Induced Ferroptotic Changes and Is Associated With Increased GPX4 Protein and Enhanced GPX4-Related SUMO3 Signaling in Hepatocellular Carcinoma Cells.","authors":"Xiang Cai, Jiangwei Ye, Linfu Fang, Xiaokun Ding, Zejun Fang, Ming Ye","doi":"10.31083/FBL53367","DOIUrl":"https://doi.org/10.31083/FBL53367","url":null,"abstract":"<p><strong>Background: </strong>Protein inhibitor of activated STAT 2 (PIAS2) is highly expressed in various solid tumors. Its precise function as a ferroptosis regulator in hepatocellular carcinoma (HCC) is still unknown. The purpose of this work was to determine whether PIAS2 overexpression attenuates erastin-induced ferroptotic changes and, in turn, is associated with the development of HCC in a manner that correlates with changes in Glutathione Peroxidase 4 (GPX4) protein levels and small ubiquitin-like modifier 3 (SUMO3) modification signals.</p><p><strong>Methods: </strong>Erastin (Era) was used to induce ferroptosis in HepG-2 and H22 cells, while Ferrostatin-1 (Fer-1) was employed for validation. Western blotting, qPCR, and co-immunoprecipitation (Co-IP) were used to examine the expression and interaction of PIAS2 and GPX4. Ferroptosis markers (lipid-reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), Fe<sup>2+</sup>), cell viability, migration, and invasion were all analyzed. Functional rescue experiments were performed using PIAS2 overexpression (oe-PIAS2) and GPX4 knockdown (sh-GPX4). In addition, a murine model of H22 cells in the right groin/lateral abdomen was established for <i>in vivo</i> validation. Tumor weight and volume were measured in these animals. Additionally, tumor tissues were collected and subjected to immunohistochemical staining for Ki-67 expression, as well as biochemical analysis of ferroptosis-related markers (GSH, MDA, Fe<sup>2+</sup>).</p><p><strong>Results: </strong>In HCC cells, Era-induced ferroptosis resulted in a significant downregulation of PIAS2 and GPX4 expression, as well as elevated levels of lipid ROS, MDA, and Fe<sup>2+</sup>, decreased GSH content, and decreased cell viability, migration, and invasion. Under Era-treated conditions, overexpression of PIAS2 effectively reversed these changes, suppressing ferroptosis and partially restoring malignant phenotypes within the context of Era challenge. Co-treatment with Fer-1 significantly reversed Era-induced ferroptotic changes and rescued cell viability, migration, and invasion, without affecting PIAS2 expression, while also restoring GPX4 levels. Mechanistic studies revealed that PIAS2 and GPX4 co-immunoprecipitate in HCC cells, and PIAS2 overexpression was associated with increased SUMO3 modification signals and higher remaining GPX4 protein levels at the examined 12- and 24-h CHX time points. GPX4 knockdown attenuated the phenotypes observed under PIAS2 overexpression, suggesting possible involvement of GPX4 in the effects of PIAS2. In Era-treated tumor-bearing mice, PIAS2 overexpression was associated with increased tumor growth, elevated Ki-67 and GPX4 levels, and reduced ferroptosis indicators.</p><p><strong>Conclusion: </strong>PIAS2 overexpression was associated with increased GPX4 SUMO3 modification signals and higher GPX4 protein levels at the examined CHX time points, together with reduced ferroptotic changes under Era-tre","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"53367"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082825","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":"From Inflamed Gingiva to Invasive Malignancy: Molecular Crosstalk in Oral Carcinogenesis: A Scoping Review.","authors":"Elena Jovanova, Angela Angjelova, Roberto Campagna, Alessandro Polizzi, Anand Marya, Gaetano Isola","doi":"10.31083/FBL53502","DOIUrl":"10.31083/FBL53502","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) develops within a complex inflammatory microenvironment where chronic mucosal inflammation and microbial dysbiosis may contribute to malignant transformation. Increasing evidence suggests that periodontal pathogens associated with chronic gingival inflammation can influence epithelial signaling, immune responses, and tumor progression. This scoping review aimed to map current molecular, genomic, and immunological evidence linking chronic gingival inflammation and periodontal pathogen-associated dysbiosis to OSCC. Following the Population-Concept-Context (PCC) framework, electronic searches were conducted in PubMed, Scopus, and Web of Science through February 2026. Original studies investigating mechanistic links between periodontal inflammation, microbial dysbiosis, and OSCC in human samples, <i>in vitro</i> models, or animal models were included. Data were extracted on microbial drivers, oncogenic signaling pathways, immune modulation, and genomic or epigenetic alterations. A total of 46 studies were included, suggesting that periodontal pathogens, particularly <i>Porphyromonas gingivalis</i> and <i>Fusobacterium nucleatum</i>, may activate oncogenic signaling pathways such as NF-κB, PI3K/Akt, Wnt/β-catenin, and TGF-β. Evidence from <i>in vitro</i>, animal, and human studies indicates that these pathways may contribute to epithelial-mesenchymal transition (EMT), tumor invasion, and resistance to apoptosis. Microbial exposure has also been associated with modulation of the tumor immune microenvironment, including macrophage polarization, suppression of cytotoxic T-cell responses, and enhanced immune checkpoint signaling. In addition, genomic and transcriptomic studies have identified dysregulated genes and microRNAs associated with inflammation-driven carcinogenesis. Overall, chronic gingival inflammation and periodontal dysbiosis appear to contribute to OSCC development through interconnected mechanisms involving inflammatory and cytokine signalling, microbe sensing and innate immune activation, immune suppression and tumor immune escape, EMT, invasion and metastatic signaling, and metabolic reprogramming with regulatory networks. However, as current evidence is largely derived from <i>in vitro</i> and animal studies with limited prospective clinical data, well-designed longitudinal human studies are needed to confirm these associations and support biomarkers discovery and novel preventive or therapeutic strategies targeting early oncogenic events in inflamed oral tissues.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"53502"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082983","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":"Multi-Omics Analyses Reveal Expression Remodeling of Key Glycolytic-Lactate Metabolic Nodes in the Pituitary of High-Altitude Sheep.","authors":"Fengyu Mao, Xia Liu, Xiaohua Du, Haifang Wang","doi":"10.31083/FBL54255","DOIUrl":"https://doi.org/10.31083/FBL54255","url":null,"abstract":"<p><strong>Background: </strong>Most studies of high-altitude adaptation in animals have focused on the heart, lung, blood, and skeletal muscle, whereas systematic evidence regarding metabolism-related expression changes in the pituitary remains limited. The pituitary is an energy-demanding neuroendocrine organ characterized by active glucose utilization and lactate production. However, multi-omics changes associated with glycolysis-lactate metabolism in the pituitary of high-altitude sheep remain undefined.</p><p><strong>Methods: </strong>Pituitary tissues from adult female sheep living at high altitude were compared with those from adult female sheep living at low altitude (n = 3 per group). Transcriptomic differences were profiled by RNA sequencing, and proteomic differences were characterized by data-independent acquisition (DIA) mass spectrometry (MS). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis, and integrated transcriptomic-proteomic analyses were used to identify representative candidates, which were further validated by reverse transcription quantitative polymerase chain reaction and western blotting.</p><p><strong>Results: </strong>RNA sequencing identified 1222 differentially expressed genes, including 690 upregulated and 532 downregulated genes, whereas DIA-MS identified 2046 differentially expressed proteins, including 1096 upregulated and 950 downregulated proteins. Functional analyses indicated enrichment of glycolysis, lactate metabolism, pyruvate metabolism, the HIF-1 signaling pathway, and oxidative phosphorylation. Gene set enrichment analysis showed significant positive enrichment of oxidative phosphorylation in the high-altitude group, whereas glycolysis/gluconeogenesis showed a positive trend without meeting the false discovery rate threshold. Integrated transcriptomic-proteomic analysis identified hexokinase 2 (HK2), enolase 2 (ENO2), and lactate dehydrogenase A (LDHA) as concordantly upregulated at both the transcript and protein levels (q-value < 0.05). Reverse transcription quantitative PCR (RT-qPCR) showed significant upregulation of <i>HK2</i>, <i>ENO2</i>, and <i>LDHA</i> (all <i>p</i> < 0.001), while western blotting confirmed increased protein expression, with HK2 reaching <i>p</i> < 0.001 and ENO2 and LDHA reaching <i>p</i> < 0.01.</p><p><strong>Conclusions: </strong>HK2, ENO2, and LDHA are stably upregulated in the pituitary of high-altitude sheep, indicating remodeling of key expression nodes associated with glycolysis-lactate metabolism. These findings provide multi-omics evidence for high-altitude-associated remodeling of selected metabolic expression nodes in the sheep pituitary.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54255"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083045","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":"Mechanism and Individualized Management of Hypertension Associated With Bruton Tyrosine Kinase Inhibitors: The <i>PCSK9/Notch3</i> Signaling Pathway.","authors":"Bingtao Li, Junling Lin, Kan Zhang, Xueqi Guo, Qi Zhang, Ji Shi, Wenjuan Wang","doi":"10.31083/FBL47763","DOIUrl":"https://doi.org/10.31083/FBL47763","url":null,"abstract":"<p><p>Bruton's tyrosine kinase inhibitors (BTKIs) have become the first-line treatment for B-cell malignancies such as chronic lymphocytic leukemia, significantly improving patient outcomes. However, hypertension is a common and critical cardiovascular adverse effect of BTKIs, with incidence rates ranging from 23% to 75%. For some patients, traditional antihypertensive therapy is ineffective, creating significant risks to cardiovascular safety and the sustainability of the treatment plan. Current reviews have primarily addressed general BTKI cardiotoxicity or isolated signaling pathways, failing to systematically analyze how the <i>proprotein convertase subtilisin/kexin type 9 (PCSK9)/Notch3</i> pathway coordinates hypertension. Furthermore, current reviews lack comprehensive integration of individual susceptibility and mechanism-targeted strategies. Thus, this review systematically evaluates the epidemiological characteristics, molecular mechanisms, individual risk-modifying factors, and management strategies of BTKI-related hypertension by searching the PubMed, Embase, and Web of Science databases (up to 2025). Key findings suggest that BTKIs induce endothelial dysfunction and increase peripheral mechanisms through multiple mechanisms. These agents promote vascular inflammation, remodeling, and altered lipid metabolism by upregulating <i>PCSK9</i>, abnormally activating <i>Notch3</i> signaling, increasing renin-angiotensin-aldosterone system activity, and driving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-reactive oxygen species-mediated oxidative stress. Additionally, off-target inhibition of TEC/interleukin 2-inducible T-cell kinase contributes to these adverse vascular effects. Disease risk is further modified by <i>Notch3/PCSK9</i> gene polymorphisms and clinical features such as existing cardiovascular disease and advanced age. Clinical management primarily relies on traditional antihypertensive drugs such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, as well as calcium channel blockers. In contrast, novel intervention strategies such as PCSK9 inhibitors and curcumin show potential advantages. To our knowledge, this review systematically elaborates the core role of the <i>PCSK9/Notch3</i> signaling pathway in BTKI-related hypertension, integrating the \"mechanism - susceptibility - intervention\" three-dimensional network, providing a theoretical basis for precise risk stratification and individualized treatment, and promoting the dual optimization of cardiovascular protection and anti-tumor therapy.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"47763"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083087","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":"LRRC3-DT Inhibits Malignant Behaviors of Hepatocellular Carcinoma and is Associated With CCDC81 Expression.","authors":"Jinglu Li, Yunfeng Luo, Mei Luo, Zhiqiang Yue, Liuxia Yuan, Huixuan Wang, Lin Chen, Linling Ju","doi":"10.31083/FBL54580","DOIUrl":"https://doi.org/10.31083/FBL54580","url":null,"abstract":"<p><strong>Background: </strong>Enhancer RNAs (eRNAs) are important regulators of tumor development and progression. Nevertheless, the diagnostic utility of circulating eRNAs in hepatocellular carcinoma (HCC) remains unclear.</p><p><strong>Methods: </strong>This was a retrospective study. The recently identified eRNA, leucine-rich repeat-containing 3 divergent transcript (LRRC3-DT), was analyzed in serum samples, tissue specimens, and various cell lines. Its diagnostic performance was evaluated alone and in combination with alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) using receiver operating characteristic (ROC) curve analysis. Functional investigations were performed to assess the biological role of LRRC3-DT by overexpressing and knocking down this eRNA in HCC cell lines. Furthermore, using transcriptome sequencing, potential target genes of LRRC3-DT were identified.</p><p><strong>Results: </strong>The serum levels of LRRC3-DT were significantly lower in patients diagnosed with HCC than in healthy controls. When LRRC3-DT was assessed alongside AFP and PIVKA-II, the combination improved sensitivity for the detection of HCC. Despite earlier research indicating that LRRC3-DT is present primarily in the nucleus and is strongly associated with tumor proliferation, invasion, and apoptosis, the serum levels of LRRC3-DT were similar between patients with HCC and those with benign liver diseases in the present study. These findings indicate limited specificity in distinguishing between these two conditions.</p><p><strong>Conclusions: </strong>Serum LRRC3-DT represents a potential auxiliary biomarker for early HCC screening; its combined use with other indicators improved diagnostic performance. However, it cannot individually discriminate HCC from benign liver disorders, and additional validation studies are warranted to confirm its differential diagnostic value.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54580"},"PeriodicalIF":3.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083103","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":"Radiotherapy Reconstitutes the Collapsed miRNome of Progressive Neuroblastoma and Promotes a Favorable Tumor Evolutionary Shift.","authors":"Sivasubramani Narayanan, Poorvi Subramanian, Sreenidhi Mohanvelu, Sheeja Aravindan, Loganayaki Periyasamy, Natarajan Aravindan","doi":"10.31083/FBL52737","DOIUrl":"https://doi.org/10.31083/FBL52737","url":null,"abstract":"<p><strong>Background: </strong>Progressive disease (PD) remains the dominant barrier to cure in high-risk neuroblastoma (HR-NB), driven in part by profound post-transcriptional deregulation that fuels clonal evolution, stemness, immune evasion, and therapy resistance. In this study, we define the molecular architecture of PD-associated microRNA (miR) collapse and demonstrate that radiotherapy (RT) acts as a potent post-transcriptional reprogrammer capable of reversing this trajectory.</p><p><strong>Methods: </strong>miRNome profiling was performed in HR-NB tumors from patients during diagnosis (Dx), intensive multi-modal clinical therapy (IMCT) defiant PD, or residual disease after incorporating RT with IMCT (RD-RT). miRs' expression profiles were validated with selective miR-320a, miR-423, miR-483-3p, miR-122-5p, miR-3184-5p, miR-21-5p qPCR. RT-influenced changes in cell-identity were investigated by assessing histomorphological alterations (H&E) and multiplex immunofluorescence (mIF) for Ki-67, PD-L1, SOX2, CD44 or p53.</p><p><strong>Results: </strong>IMCT-defying PD displayed a loss of 167 miRs, and none upregulated, corresponding an evolutionary fingerprint for pathways governing cancer stem cell (CSC) maintenance, epithelial to mesenchymal transition (EMT), metabolic rewiring, proliferative fitness, and immune suppression. Strikingly, adding RT reversed 146 of these miRs and induced additional 179 RT-specific miRs, restoring regulatory networks governing apoptosis, p53-mediated DNA-damage response, differentiation/mesenchymal to epithelial transition (MET), and immune visibility. Individual miR-qPCR analysis of miR-320a, miR-483-3p, miR-3184-5p miR-21-5p, and miR-122-5p validated and corroborated the array expression outcomes. Histologic and mIF remarkably substantiated these miR signatures, showing that RT transforms poorly differentiated, plastic, PD-L1⁺/SOX2⁺/CD44⁺ CSC-like PD tumors into differentiated, lineage-stabilized, immune-permissive states characterized by neuropil restoration, ganglioneuroma-like maturation, marginal yet measurable loss of SOX2/CD44, suppression of PD-L1, complete collapse of Ki-67⁺ proliferative compartments, and significant induction of p53.</p><p><strong>Conclusion: </strong>Collectively, our findings indicated that RT could be a global regulator of tumor state transitions, reinstating miR-mediated governance lost during PD evolution and redirecting tumor fate toward regression. Our results provide proof-of-concept evidence that RT delivers powerful molecular benefits beyond local control, introducing a conceptual framework for miR-guided RT personalization, biomarker development, and rational combination strategies to improve outcomes in HR-NB.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"52737"},"PeriodicalIF":3.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082874","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":"Heart Failure: Lipid Metabolism Disorders Driving Cellular Senescence Through a Vicious Cycle, and Possible Intervention Strategies.","authors":"Wei He, Pan Liu, Jingjing Kong, Qing Wang, Yangqi Zhao, Ran Xia","doi":"10.31083/FBL48959","DOIUrl":"https://doi.org/10.31083/FBL48959","url":null,"abstract":"<p><p>Heart failure (HF) is major and growing global health challenge, with lipid metabolism dysregulation recognized as a significant contributing factor. This review focuses on the emerging concept of the \"metabolism-senescence axis\", which plays a central role in disease development progression. Excess lipid metabolites, especially ceramides and diacylglycerols, contribute to cardiomyocyte injury through multiple mechanisms, including mitochondria dysfunction, promoting oxidative stress, and interfering with normal metabolic signals. The senescence-associated secretory phenotype (SASP) promotes a pro-senescent tissue microenvironment, thereby disrupting the normal metabolic balance and creating a vicious cycle that seriously affects heart structure and function. This review examines the molecular events underlying this process, including cellular injury, impaired fatty acid oxidation, oxidative stress, activation of the p53/p21 and p16INK4a/Rb, signaling pathways, and SASP-mediated metabolic dysfunction. We further discuss the rationale for combinatorial strategies targeting both metabolic dysfunction and cellular senescence, proposing that simultaneous intervention in these interconnected pathways may represent a promising therapeutic approach to delay the progression of HF and improve patient outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"48959"},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083084","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":"Glioma Pathogenesis and Treatment Modality: Novel Insights From Midkine Research.","authors":"Tianyuan Zhao, Xuehui Pang, Xiaonan Xi, Feimeng Zhou","doi":"10.31083/FBL52445","DOIUrl":"https://doi.org/10.31083/FBL52445","url":null,"abstract":"<p><p>Gliomas, the most common and aggressive primary tumors in the central nervous system, are characterized by high invasiveness and resistance to therapy, making them a major focus of neuro-oncology research. Although substantial progress has been achieved in elucidating their molecular underpinnings in recent years, effective treatment modalities remain limited owing to their complex pathogenesis and tumor microenvironment. Midkine (MDK), a multifunctional growth factor, has increasingly been implicated in glioma pathogenesis and biology. MDK not only contributes to tumor cell proliferation, migration, and therapy resistance, but also plays a pivotal role in modulating the tumor microenvironment. Notably, MDK functions as both an intrinsic oncogenic driver and an extrinsic modulator of the tumor microenvironment, in to the molecular mechanisms underlying glioma pathogenesis that is critical to the formulation of effective treatments, have not comprehensively reviewed. This review summarizes the roles of MDK in various signaling pathways and summarizes recent advances in unraveling the expression patterns and functional roles of MDK and their therapeutic implications and potential as treatment targets for gliomas.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"52445"},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083073","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":"Mechanisms of Complement Activation and NETosis Interplay in Early Pregnancy Loss: From Autoimmunity to Thrombogenesis.","authors":"Junxian Ma, Kexin Wang, Guosheng Li, Fang Wang","doi":"10.31083/FBL49518","DOIUrl":"https://doi.org/10.31083/FBL49518","url":null,"abstract":"<p><p>Early Pregnancy Loss (EPL) represents a formidable challenge in reproductive medicine. Its complex pathophysiology is primarily characterized by dysregulation of both the immune and coagulation systems. In recent years, abnormal activation of the complement system and neutrophil extracellular trap formation (NETosis) have received increasing scientific attention as key molecular events underlying EPL. This interest is fueled significantly by compelling evidence from non-pregnant models, such as antiphospholipid syndrome (APS) and severe infections (e.g., COVID-19), which demonstrate a pathogenic synergy between complement and NETosis in thrombo-inflammatory pathways. Dysregulation of the complement system can trigger strong inflammatory responses and promote a prothrombotic state. Similarly, excessive NETosis acts as a significant driver of tissue damage and thrombosis. This review aims to systematically delineate the complex crosstalk between complement activation and NETosis in EPL, with particular emphasis on their bidirectional regulatory relationship within autoimmune and thrombo-inflammatory pathways. By thoroughly analyzing the critical pathological role of this \"complement-NETosis axis\" in disrupting uteroplacental interface homeostasis and ultimately causing pregnancy failure, this review not only presents an integrative conceptual framework for comprehensively understanding the molecular mechanisms of EPL, but, more importantly, proposes a novel hypothesis, based on mechanistic insights derived from non-pregnant models, that this axis may play acentral role in EPL. This perspective provides a framework for future research, encompassing the validation of associated potential biomarkers and the exploration of targeted intervention strategies, thereby holding promise for advancing precise clinical intervention paradigms for specific EPL subtypes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"49518"},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083037","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":"Genome-Wide Characterization, Expression Profiling and Source-Sink Nitrogen Responses of Rice <i>Glutamine Synthetase</i> Gene Family.","authors":"Haiting Hu, Huihui Zhang, Zixin Xiang, Yuelin Wu, Shuai Fu, Zhuocheng Liu, Han Yang","doi":"10.31083/FBL54457","DOIUrl":"https://doi.org/10.31083/FBL54457","url":null,"abstract":"<p><strong>Background: </strong>Nitrogen is the most abundant mineral nutrient required by rice (<i>Oryza sativa</i>) and the primary limiting factor for grain yield. Glutamine synthetase (GS) is a key enzyme involved in nitrogen assimilation in rice, and is closely associated with nitrogen use efficiency (NUE) and source-sink nitrogen dynamics.</p><p><strong>Methods: </strong>We performed a genome-wide characterization of the <i>GS</i> gene family across 12 plant species. Haplotype analysis of four rice <i>GS</i> genes was conducted using resequencing data from approximately 2000 rice accessions. A reproductive-stage nitrogen-gradient experimental system (0N, 1N, 3N) was established to simultaneously profile <i>GS</i> transcript levels and enzyme activity in source tissues (roots and flag leaves) and sink tissues (young embryos at different developing stages).</p><p><strong>Results: </strong>A total of 86 non-redundant GS proteins were identified, which clustered into two evolutionarily distinct subfamilies (GS1 and GS2). In rice, <i>OsGS1-1</i> exhibited pronounced indica-japonica differentiation and a pattern consistent with a domestication bottleneck, while other members showed high sequence conservation. Transcript abundance and enzymatic activity data revealed that <i>OsGS1‑3</i> among <i>GS</i> isoforms exhibited its highest transcript level at 5 days after pollination (DAP), while total GS activity peaked at 5 DAP in developing embryos, suggesting this stage may represent a critical window for active nitrogen assimilation during embryogenesis. Distinct tissue-specific expression patterns and nitrogen-responsive profiles were also observed among <i>OsGS</i> isoforms.</p><p><strong>Conclusions: </strong>These findings provide fundamental insights into the evolutionary and functional diversification of the rice <i>GS</i> gene family. The tissue-specific and nitrogen-dependent transcriptional and enzymatic responses of <i>GS</i> isoforms indicate their coordinated involvement in nitrogen assimilation processes, which may further influence source-sink nitrogen utilization in rice under varying nitrogen conditions.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 9","pages":"54457"},"PeriodicalIF":3.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082991","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}