Frontiers in Cell and Developmental Biology最新文献

{"title":"Zebrafish model for studying vascular development and vascular-related disease.","authors":"Hadeel T Zedan, Fatma H Ali, Himanshu Gaur, Ramani Ramchandran, Huseyin C Yalcin","doi":"10.3389/fcell.2026.1872737","DOIUrl":"https://doi.org/10.3389/fcell.2026.1872737","url":null,"abstract":"<p><p>Zebrafish (<i>Danio rerio</i>) is a powerful vertebrate animal model system for cardiovascular research. Their small size, optical transparency, fecundity, rapid development, remarkable regenerative capacity, and the availability of numerous fluorescent transgenic lines have made them an excellent experimental model for studying vascular development and disease. There is a high degree of conservation in the anatomy and physiology of the zebrafish vascular system relative to other vertebrates, thereby enabling zebrafish to model human vascular pathophysiology. Questions concerning genetic vascular disorders, including endothelial dysfunction, flow-induced alterations, lipid metabolism, atherosclerosis, and tumor angiogenesis, have been extensively studied in zebrafish. In this review, we describe the contribution of the zebrafish system to the current understanding of blood vessel formation and the use of zebrafish for modelling human diseases caused by dysregulated vasculatures. We also summarize the techniques, methods, and transgenic lines used to image and assess zebrafish vasculature and to study its role in the development and pathogenesis of cardiovascular conditions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1872737"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic biomarkers for cancer vaccine development: from cancer cell biology to neoantigen-guided precision immunotherapy.","authors":"Dario Rusciano","doi":"10.3389/fcell.2026.1897032","DOIUrl":"https://doi.org/10.3389/fcell.2026.1897032","url":null,"abstract":"<p><p>Cancer vaccines have resurged in oncology because they address a central question in precision medicine: whether the molecular identity of a tumor can be converted into an immune target that is both specific and clinically useful. Preventive vaccines against oncogenic viruses have already shown that immune intervention can reduce the burden of virus-associated cancers. Therapeutic cancer vaccines face a more difficult task, because established tumors arise from self-tissues, change over time, and often acquire mechanisms that limit antigen presentation, T-cell entry, or immune-mediated killing. This review examines cancer vaccines as biomarker-driven tools within precision oncology. The focus is not only on vaccine platforms, but on the biological requirements that make an antigen suitable for therapeutic targeting. Tumor-specific mutations, viral antigens, recurrent driver alterations, frameshift peptides, cancer-testis antigens, and personalized neoantigens may all provide vaccine targets, but their presence alone is not enough. A clinically relevant vaccine antigen should be expressed by tumor cells, processed and presented through HLA molecules, recognized by functional T cells, and sufficiently retained during tumor evolution. This distinction is particularly important because sequencing and computational prediction now generate many candidate neoantigens whose immunological relevance still requires experimental confirmation. Particular attention is given to antigen-presentation defects, clonal and subclonal heterogeneity, tumor microenvironment barriers, circulating tumor DNA-defined minimal residual disease, and immune-response monitoring. Colorectal cancer is used as a working model because microsatellite instability-high/mismatch repair-deficient tumors, microsatellite-stable tumors with immune-resistant features, and recurrent alterations in MMR genes, KRAS, BRAF, adenomatous polyposis coli, and TP53 illustrate how cancer-cell signaling, neoantigen generation, tumor microenvironment remodeling, and patient stratification intersect. Overall, cancer vaccines are unlikely to become universal stand-alone treatments for advanced solid tumors. Their most credible role may emerge in molecularly selected patients, adjuvant therapy, minimal residual disease, virus-associated malignancies, and rational combinations with checkpoint inhibitors or tumor microenvironment-modulating agents.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1897032"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"18β-glycyrrhetinic acid inhibits lung adenocarcinoma progression by targeting the MET/AKT signaling axis.","authors":"Gongyu Wu, Huilin Guan, Mengyao Lv, Zhiqiang Chen, Changjiu Gao, Wanzhen Su, Hui Fu","doi":"10.3389/fcell.2026.1752632","DOIUrl":"https://doi.org/10.3389/fcell.2026.1752632","url":null,"abstract":"<p><strong>Background: </strong>18β-Glycyrrhetinic acid (18β-GA), a major bioactive triterpenoid from licorice, has demonstrated anti-cancer potential; however, its mechanisms against lung adenocarcinoma (LUAD) remain unclear.</p><p><strong>Methods: </strong>This study employed an integrated approach combining network pharmacology, bioinformatics, and experimental validation to investigate the anti-LUAD efficacy and underlying molecular targets of 18β-GA.</p><p><strong>Results: </strong><i>In vitro</i> and <i>in vivo</i> assays demonstrated that 18β-GA dose-dependently inhibited LUAD cell proliferation, migration, and colony formation, while significantly suppressing tumor growth in a Lewis lung carcinoma (LLC) allograft model. By integrating network pharmacology with TCGA transcriptomic data, MET was identified as a core upstream target, and the PI3K/AKT signaling pathway was revealed as a significantly enriched pathway. Molecular docking and molecular dynamics simulations revealed that 18β-GA forms stable, high-affinity complexes in the catalytic pockets of both MET and AKT. Subsequent biological validations confirmed that 18β-GA attenuated the phosphorylation of critical signaling components, including MET, PI3K, AKT, and mTOR, without altering their mRNA or total protein expression. Crucially, functional rescue assays revealed that exogenous MET activation via its specific ligand HGF simultaneously reversed the 18β-GA-induced suppression of both p-MET and p-AKT. In contrast, the AKT agonist SC79 effectively restored p-AKT levels and reversed the anti-tumor efficacy of 18β-GA, but it failed to rescue the inhibition of upstream p-MET. This unidirectional reversal rigorously validates MET as the upstream regulator of AKT.</p><p><strong>Conclusion: </strong>18β-GA suppresses LUAD by targeting upstream MET to drive a top-down cascade blockade of the PI3K/AKT/mTOR signaling pathway, providing a pharmacological rationale for its application in LUAD targeted therapy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1752632"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.","authors":"Mengmeng Chen, Ning Zuo, Qi Wang, Hongyang Zhao, Pengdan Dai, Shaoshuai Liang, Wei Zhu, Haoyun Zhang, Muhammad Omer Iqbal, Dingcai Dong, Bingqiang Zhang","doi":"10.3389/fcell.2026.1931336","DOIUrl":"https://doi.org/10.3389/fcell.2026.1931336","url":null,"abstract":"<p><p>Cell reprogramming can transform somatic cells into induced pluripotent stem cells providing a platform for patient-specific disease modeling, drug screening and regenerative medicine research. Since the advent of OKSM-mediated reprogramming, the system of technical approaches has evolved continuously - from integrated viral vectors to non-integrated episomal systems and, more recently, chemical reprogramming and CRISPR approaches. The simultaneous advances in single-cell multi-omics, biomaterials engineering, and artificial intelligence have further refined the controllability and precision of the reprogramming process. Despite these innovations, problems persist that hinder clinical translation: incomplete epigenetic resetting, ongoing clonal heterogeneity, genomic instability in long-term culture, and the lack of standardized Good Manufacturing Practice protocols for large-scale manufacturing. This review summarizes the trajectory of iPSC reprogramming technologies, with special emphasis on the translational applicability of each modality. We evaluated viral and nonviral delivery systems, chemical reprogramming, strategies that aid gene editing, and emerging engineering platforms, including microfluidics, smart biomaterials, and artificial-intelligence-driven process optimization. We further identify the core \"translational triltrilas\", namely, the inherent tradeoffs between security, homogeneity, and scalability, and propose a comprehensive strategy to overcome these bottlenecks. By linking basic mechanistic understandings with industrial and regulatory considerations, this review aims to provide a route for transitioning iPSC technology from a laboratory tool to a clinically viable manufacturing platform.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1931336"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sufentanil attenuates LPS-induced acute lung injury by suppressing ferroptosis and maintaining GPX4 protein abundance.","authors":"Xiaoyun Guo, Weifeng Yan, Wenyong Peng, Runbin Yan","doi":"10.3389/fcell.2026.1858772","DOIUrl":"https://doi.org/10.3389/fcell.2026.1858772","url":null,"abstract":"<p><strong>Introduction: </strong>Acute lung injury (ALI) is a severe inflammatory syndrome characterized by disruption of the alveolar-capillary barrier, pulmonary edema, and impaired gas exchange. Ferroptosis has emerged as an important contributor to ALI pathogenesis, but the mechanisms associated with reduced glutathione peroxidase 4 (GPX4) protein abundance during lung injury remain incompletely understood.</p><p><strong>Methods: </strong>This study investigated the protective effects of sufentanil pretreatment against lipopolysaccharide (LPS)-induced ALI and examined whether these effects were associated with ferroptosis suppression and maintenance of GPX4 protein abundance. A mouse model of LPS-induced ALI and LPS-stimulated A549 cells were used to evaluate the effects of sufentanil <i>in vivo</i> and <i>in vitro</i>. The contribution of GPX4 was assessed using siRNA-mediated knockdown and pharmacological modulation of ferroptosis. Potential CMArelated lysosomal involvement was explored using pathway inhibition, coimmunoprecipitation, colocalization analysis, and LAMP2A knockdown.</p><p><strong>Results: </strong>Sufentanil pretreatment alleviated LPS-induced lung injury, reduced inflammatory responses, and attenuated ferroptosis-associated alterations <i>in vivo</i>. In A549 cells, sufentanil reduced mitochondrial and lipid reactive oxygen species, intracellular Fe2+ accumulation, mitochondrial damage, and ACSL4 upregulation, while restoring GPX4 and SLC7A11 protein abundance. GPX4 knockdown markedly attenuated the protective effects of sufentanil. The maintenance of GPX4 protein abundance observed after sufentanil pretreatment was accompanied by reduced GPX4-LAMP2A colocalization and reduced association between GPX4 and HSC70. Furthermore, erastin partially reversed the protective effects of sufentanil <i>in vivo</i>.</p><p><strong>Discussions: </strong>These findings support a preconditioning effect of sufentanil against LPS-induced ALI, associated with ferroptosis suppression, maintenance of GPX4 protein abundance, and possible CMA-related lysosomal involvement.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1858772"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics integration reveals TIM-4 as a master regulatory hub of neuroinflammation and neuronal cell death.","authors":"Liang Chen, Yan-Yan Li, Li Han, Shiqi Lu","doi":"10.3389/fcell.2026.1876873","DOIUrl":"https://doi.org/10.3389/fcell.2026.1876873","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is a leading cause of severe disability, frequently resulting in persistent cognitive dysfunction. Microglial M1/M2 polarization is critically involved in TBI pathogenesis, yet its molecular regulatory mechanisms remain poorly understood. TIM-4, a TIM family member implicated in cerebral ischemia-reperfusion injury, has an unknown function in TBI-particularly regarding its regulation of neuronal death.</p><p><strong>Methods: </strong>We employed a comprehensive multi-omics strategy integrating bulk RNA-seq, publicly available single-cell RNA sequencing (scRNA-seq; GEO: GSE101901), weighted gene co-expression network analysis (WGCNA), quantitative proteomics, phosphoproteomics, and epigenomic profiling (ATAC-seq and H3K27ac ChIP-seq) to systematically investigate TIM-4 in TBI. Functional validation included TIM-4 knockdown experiments, TUNEL apoptosis detection, Golgi staining for dendritic spine analysis, and behavioral assessments.</p><p><strong>Results: </strong>TIM-4 was the most significantly upregulated gene and protein across all omics layers, with expression positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory markers. ScRNA-seq revealed TIM-4 upregulation was restricted to activated M1-like microglia, and pseudotime trajectory analysis demonstrated TIM-4-driven M1 polarization. WGCNA identified a TIM-4-associated co-expression module strongly correlated with TBI severity and behavioral outcomes (r = 0.92, p < 0.001). Phosphoproteomics identified TIM-4 Y⁴⁶ hyper-phosphorylation as a key post-translational regulatory event, and ATAC-seq/ChIP-seq revealed NF-κB-driven chromatin remodeling at the TIM-4 locus. Multi-omics integration ranked TIM-4 as the master regulatory hub (composite evidence score = 0.89). Functionally, TIM-4 knockdown promoted microglial M2 polarization, reduced neuronal apoptosis and dendritic spine loss, and significantly improved spatial memory deficits and motor coordination following TBI.</p><p><strong>Conclusion: </strong>TIM-4 is established as a critical driver of neuroinflammation-associated neuronal death in TBI, representing a promising therapeutic target for TBI-related cognitive dysfunction.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1876873"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the application of nanoparticles for the diagnosis and treatment of diabetic cardiomyopathy.","authors":"Jia Feng, Yuqing Huang, Yufeng He, Chenhao Deng, Zongzhe Jiang, Qifu Li, Yu Li, Xiaorong Lan, Yong Xu","doi":"10.3389/fcell.2026.1912847","DOIUrl":"https://doi.org/10.3389/fcell.2026.1912847","url":null,"abstract":"<p><p>As a frequent and serious cardiovascular complication of diabetes mellitus, diabetic cardiomyopathy (DCM) typically presents with an asymptomatic onset during its initial phase, followed by gradual worsening over time. Currently, no universally accepted and effective DCM-specific targeted therapeutic strategy is available. Recently, nanotechnology has gained recognition as a viable strategy to address the shortcomings of traditional treatments, leveraging its size-dependent effects, large specific surface area, and ability to integrate multiple functions. This article presents a structured summary of recent developments regarding nanoparticle utilization for diagnostic and therapeutic purposes in DCM. First, from a functional perspective, we analyze the core advantages of nanoparticles in improving pharmacokinetic profiles, enhancing drug stability and bioavailability, facilitating targeted myocardial delivery, enabling pathological microenvironment-responsive release, and constructing theranostic platforms. Second, according to material type, we discuss the current research status and the operational mechanisms of different nanocarrier systems-including polymeric nanoparticles, liposomes, inorganic nanoparticles, and extracellular vesicles-in antifibrotic therapy, antioxidation intervention, regulation of energy metabolism, and early diagnostic assessment. Finally, based on current limitations and successful experience from other cardiovascular diseases we outline future directions, including biomimetic design, upgraded targeting strategies, diversified administration routes, safety evaluation, and combined applications with hydrogels or myocardial patches. Although nanotechnology has shown promising potential in animal models of DCM, clinical translation still requires continued breakthroughs in material innovation, quality control, and long-term safety validation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1912847"},"PeriodicalIF":5.3,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal circadian disruption during pregnancy and offspring diabetic cardiovascular disease risk.","authors":"Saman Saedi, Hailong Bing, Jiaxing Wu, Yaoxin Gao, Chunyan Wang, Qinjun Chu, Zhengyuan Xia","doi":"10.3389/fcell.2026.1879135","DOIUrl":"10.3389/fcell.2026.1879135","url":null,"abstract":"<p><p>Circadian rhythm disruption during pregnancy has been recognized as a growing public health concern, affecting approximately 20% of the workforce due to shift work and prevalent lifestyle-related factors. Grounded in the developmental origins of health and disease (DOHaD) paradigm, emerging evidence indicates that maternal circadian disruption (MCD) may have profound transgenerational effects, programming offspring susceptibility to diabetes mellitus and its cardiovascular complications. This narrative review synthesizes current mechanistic evidence linking MCD to offspring cardiometabolic disease (CMD), emphasizing the integrated clock-metabolic-oxidative stress axis. Disruption of core clock genes, including <i>CLOCK</i>, <i>BMAL1</i>, and <i>CRY</i>/<i>PER</i>, lead to impaired glucose homeostasis, mitochondrial function, and antioxidant defense, subsequently promoting generation of reactive oxygen species (ROS) and exacerbating oxidative stress. These disturbances contribute to endothelial dysfunction, vascular inflammation, and accelerated atherogenesis in offspring. Chronotherapeutic approaches, particularly melatonin supplementation and circadian-aligned lifestyle modifications, represent promising strategies in mitigating these programmed deficits. Elucidating this clock-metabolic-oxidative stress axis will provide essential insights to develop preventive and therapeutic interventions to address the developmental origins of CMD across generations.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1879135"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted astrocyte-neuron metabolic coupling in amyotrophic lateral sclerosis.","authors":"Áine Bríd Heffernan, Florence Do, Eleanor Carter, Farah Al-Tameemi, Bhuvaneish T Selvaraj, Maria Stavrou","doi":"10.3389/fcell.2026.1899307","DOIUrl":"10.3389/fcell.2026.1899307","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by progressive loss of motor neurons. In addition to neurodegeneration, ALS is increasingly recognised as a disorder associated with widespread metabolic dysfunction, including hypermetabolism, weight loss, and dyslipidaemia, all of which correlate with disease progression and survival. Astrocytes play a central role in maintaining metabolic homeostasis in the central nervous system by supporting neuronal energy demands, regulating glutamate levels, buffering oxidative stress, and maintaining lipid balance. Emerging evidence suggests that disruption of these supportive astrocytic functions may contribute directly to motor neuron vulnerability in ALS. In this mini-review, we discuss how alterations in astrocyte metabolism may impair astrocyte-neuron metabolic coupling in ALS. We summarise work from human studies and experimental models demonstrating abnormalities in astrocytic glycolysis, mitochondrial function, lactate shuttling, lipid metabolism, and glutamate homeostasis. We highlight growing evidence implicating mitochondrial dysfunction and impaired lipid handling in astrocytes as important contributors to disease progression. We explore how these changes may deprive motor neurons of metabolic and antioxidant support while also promoting excitotoxicity, oxidative stress, and lipotoxicity. We also discuss how recent advances in human induced pluripotent stem cell models, metabolomics, and single-cell transcriptomics are improving our understanding of astrocyte dysfunction in ALS. Finally, we consider current and emerging therapeutic strategies aimed at restoring astrocytic metabolic function. Together, these findings support the idea that progressive failure of astrocyte-mediated metabolic support is an important component of ALS pathogenesis and may represent a promising therapeutic target.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1899307"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nauclea officinalis extract rescues working memory deficits in adolescent maternal immune activation offspring by restoring cholinergic signaling.","authors":"Lei An, Zhanyong Li, Yan Wang, Lin Feng, Wei Sun","doi":"10.3389/fcell.2026.1918425","DOIUrl":"10.3389/fcell.2026.1918425","url":null,"abstract":"<p><strong>Objective: </strong>Maternal immune activation (MIA) is a key risk factor for schizophrenia-related cognitive deficits, linked to prefrontal cholinergic dysfunction. Nauclea officinalis extract (NOE) possesses documented anti-inflammatory and neuroprotective properties, but its effects on MIA-induced cognitive and neuronal dysfunctions are unknown. This study aimed to investigate whether NOE ameliorates MIA-induced working memory deficits by modulating infralimbic medial prefrontal cortex (IL-mPFC) cholinergic signaling and neuronal activity.</p><p><strong>Methods: </strong>Using a poly (I:C)-induced MIA rat model, adolescent offspring were treated with NOE (5, 10 and 20 mg/kg). Behavioral tests, <i>in vivo</i> electrophysiology, and molecular assays were conducted.</p><p><strong>Results: </strong>NOE dose-dependently attenuated MIA-induced neuroinflammation (IL-1β, IL-6, TNF-α) in the IL-mPFC. It restored acetylcholine (ACh) levels, reduced acetylcholinesterase (AChE) activity, but did not alter M1/M3 receptor expression. NOE (20 mg/kg) significantly improved 30-s delay working memory performance, an effect blocked by the muscarinic receptor antagonist scopolamine (SCO) and mimicked by the AChE inhibitor physostigmine (PHY). Electrophysiologically, NOE rescued MIA-impaired long-term potentiation (LTP) and paired-pulse ratio (PPR), and enhanced delay-related firing of IL pyramidal neurons. These restorative effects were similarly replicated by PHY and antagonized by SCO.</p><p><strong>Conclusion: </strong>NOE alleviates MIA-induced working memory deficits by reducing neuroinflammation and, crucially, by functionally potentiating cholinergic transmission in the IL-mPFC. The findings highlight the IL cholinergic system as a critical therapeutic target and position NOE as a promising multi-target agent for cognitive impairments in neurodevelopmental disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1918425"},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}