Frontiers in Cell and Developmental Biology最新文献

{"title":"Evaluating multiple large language models on orbital diseases.","authors":"Qi-Chen Yang, Yan-Mei Zeng, Hong Wei, Cheng Chen, Qian Ling, Xiao-Yu Wang, Xu Chen, Yi Shao","doi":"10.3389/fcell.2025.1574378","DOIUrl":"10.3389/fcell.2025.1574378","url":null,"abstract":"<p><p>The avoidance of mistakes by humans is achieved through continuous learning, error correction, and experience accumulation. This process is known to be both time-consuming and laborious, often involving numerous detours. In order to assist humans in their learning endeavors, ChatGPT (Generative Pre-trained Transformer) has been developed as a collection of large language models (LLMs) capable of generating responses that resemble human-like answers to a wide range of problems. In this study, we sought to assess the potential of LLMs as assistants in addressing queries related to orbital diseases. To accomplish this, we gathered a dataset consisting of 100 orbital questions, along with their corresponding answers, sourced from examinations administered to ophthalmologist residents and medical students. Five language models (LLMs) were utilized for testing and comparison purposes, namely, GPT-4, GPT-3.5, PaLM2, Claude 2, and SenseNova. Subsequently, the LLM exhibiting the most exemplary performance was selected for comparison against ophthalmologists and medical students. Notably, GPT-4 and PaLM2 demonstrated a superior average correlation when compared to the other LLMs. Furthermore, GPT-4 exhibited a broader spectrum of accurate responses and attained the highest average score among all the LLMs. Additionally, GPT-4 demonstrated the highest level of confidence during the test. The performance of GPT-4 surpassed that of medical students, albeit falling short of that exhibited by ophthalmologists. In contrast, the findings of the study indicate that GPT-4 exhibited superior performance within the orbital domain of ophthalmology. Given further refinement through training, LLMs possess considerable potential to be utilized as comprehensive instruments alongside medical students and ophthalmologists.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1574378"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682336","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":"VE-PTP controls a fluid shear stress set point that governs cell morphological responses through Tie-2.","authors":"Keisuke Shirakura, Mana Ghanbarpour Houshangi, Kevin G Peters, Dietmar Vestweber","doi":"10.3389/fcell.2025.1603517","DOIUrl":"10.3389/fcell.2025.1603517","url":null,"abstract":"<p><p>Blood flow differs between arteries and veins, hence endothelial cells in these vessels are exposed to different magnitudes of shear stress. Deviation from physiological blood flow triggers vascular remodeling, with increased or decreased flow leading to outward or inward remodeling, to adjust lumen diameter and thereby re-establish physiological shear stress. Based on this, it is assumed that endothelial cells in different vessels differ in their sensitivity to different shear stress levels. Expression levels of VEGFR3 were previously demonstrated to determine the threshold or set point for endothelial cell type specific shear stress sensitivity. Here we show, that the receptor type tyrosine phosphatase VE-PTP and the tyrosine kinase receptor Tie-2 represent another, new signaling system, that determines sensitivity and cellular responsiveness to different shear stress magnitudes or flow set points. We found that increased shear stress levels cause increased levels of VE-PTP endocytosis, which trigger, a similarly graded increase of Tie-2 activity, stimulation of FOXO1 nuclear exclusion and activation of autophagy. The VE-PTP/Tie-2 signaling mechanism controls cell alignment and elongation dependent on the magnitude of shear stress. In addition, VE-PTP/Tie-2 controls shear stress-induced cellular morphological changes independent of VEGFR2. Thus, VE-PTP/Tie-2 is a novel signaling mechanism which determines shear stress sensitivity and morphological responses of endothelial cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1603517"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674346","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":"Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer.","authors":"Helena Reyes-Gopar, Keila Adonai Pérez-Fuentes, Matthew L Bendall, Enrique Hernández-Lemus","doi":"10.3389/fcell.2025.1597245","DOIUrl":"10.3389/fcell.2025.1597245","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) accounts for twelve percent of all breast cancer cases, with a survival rate around ten percent lower than ER+/PR+ positive breast cancers. There are limited therapeutic options as these tumors do not respond to hormonal therapy or HER2-targeted treatments. We hypothesized that new insights into pathogenic mechanisms in TNBC can be obtained from studying epigenetic alterations through Hi-C (genome-wide chromosome conformation capture) data analysis.</p><p><strong>Methods: </strong>We developed a computational strategy that captured key properties of chromatin conformation while incorporating statistical measures of interaction significance. This model addresses limitations in Hi-C data analysis without relying on predefined features like TADs and compartments. We applied this model to Hi-C and RNA-seq data from TNBC patients, representing the data as multilayer networks to identify genome-wide properties of the TNBC 3D genome.</p><p><strong>Results: </strong>Our network-based analysis revealed distinct chromatin interaction patterns in TNBC compared to healthy contralateral controls. Hi-C data can distinguish interaction patterns related to diseased phenotypes or interaction patterns with potential to exert regulatory effects instead of incidental contacts, but some apparently random interactions may also support important genome regulatory activities.</p><p><strong>Discussion: </strong>Our findings demonstrate that network-based Hi-C analysis can capture the genome-wide complexity of chromatin interactions in TNBC. This integrative approach provides new insights into the epigenetic mechanisms underlying TNBC pathogenesis and contributes to the advancement of analysis methods for future investigations into novel therapeutic targets.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1597245"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674344","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":"Involvement of role of HMGB1-NLRP3 pathway in systemic disorders.","authors":"Lei Yang, Xue Li, Xiaoming Zhu, Futao Ge, Yuantao Wang","doi":"10.3389/fcell.2025.1600596","DOIUrl":"10.3389/fcell.2025.1600596","url":null,"abstract":"<p><p>High mobility group box-1 (HMGB1) is a protein released from stressed or damaged cells that triggers immune activation and chronic inflammation. The NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) is a central component of the inflammasome, which activates caspase-1 and releases pro-inflammatory cytokines, including IL-1β and IL-18. The HMGB1/NLRP3 axis plays a critical role in regulating inflammation and immune responses, driving systemic inflammation and disease progression. Targeting this pathway offers promising therapeutic strategies for conditions such as autoimmune disorders, trauma, and chronic inflammatory diseases. In particular, inhibiting HMGB1 or NLRP3 can mitigate the exaggerated inflammatory response, reduce tissue damage, and slow disease progression. This review explores the bidirectional interactions between HMGB1 and NLRP3 and discusses current and emerging therapeutic approaches targeting this axis to modulate inflammation and improve clinical outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1600596"},"PeriodicalIF":4.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674345","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":"Selective blockade of acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection.","authors":"Jiaai Li, Yu Cheng, Di Ma, Guangjian Li, Weixuan Zhao, Ting Jiang, Hongmei Meng","doi":"10.3389/fcell.2025.1582970","DOIUrl":"10.3389/fcell.2025.1582970","url":null,"abstract":"<p><strong>Background: </strong>Acid-sensing ion channel 1a (ASIC1a) is the only member of the ASIC family where Ca²⁺ osmosis has been reported, and it is highly expressed in neurons of the central nervous system. This study aimed to investigate whether ASIC1a is trafficked to the plasma membrane and regulated by the Rho/ROCK and PI3K signaling pathways in temporal lobe epilepsy (TLE). In addition, further research is required to determine whether selective ASIC1a blockade is a viable therapeutic strategy for TLE.</p><p><strong>Methods: </strong>The localization and expression levels of ASIC1 and mRNA levels of ASIC1a were detected when the Rho/ROCK and PI3K signaling pathways were activated and inhibited in glutamate (Glu)-induced cell. Meanwhile, we analyzed the location and expression of ASIC1 using Western blotting and immunofluorescence in brain tissue samples from TLE patients, kainic acid (KA)-treated rats, and Glu-induced primary hippocampal neurons. Currently, no specific ASIC1a antibody is available, so the ASIC1 antibody was used in this study, as in previous studies. Furthermore, we evaluated the HT22 cell survival rate, mitochondrial damage, apoptosis, and autophagy to examine whether selective blocking ASIC1a (PcTx1) could play a neuroprotective role.</p><p><strong>Results: </strong>First, the Rho/ROCK and PI3K signaling pathways affect the regulation of the expression and localization of ASIC1, especially the mRNA levels of ASIC1a in the Glu-induced HT22 cell injury model. Second, the high expression of ASIC1 in epilepsy patients was verified in all three sample types, and the phenomenon of its transport from the cytoplasm to the cell membrane/mitochondria was confirmed. Finally, although ASIC1 has a limited epileptogenic effect in the acute phase of epilepsy <i>in vivo</i>, selective blockade of ASIC1a using PcTx1 provided significant hippocampal neuroprotection and reduced mitochondrial damage, apoptosis, and cellular autophagy <i>in vitro</i>.</p><p><strong>Interpretation: </strong>This study is a systematic report concerning ASIC1a in temporal lobe epilepsy, including <i>in vivo</i> and <i>in vitro</i> experiments addressing both the acute and chronic phases. It provides foundational research for proposing ASIC1a as a new target for epilepsy treatment.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1582970"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658819","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":"How the chromatin landscape influences nuclear morphology.","authors":"Sourabh Sengupta, Haritha Prabha, Daniel L Levy","doi":"10.3389/fcell.2025.1634252","DOIUrl":"10.3389/fcell.2025.1634252","url":null,"abstract":"<p><p>Nuclear morphology is a defining cellular feature, differing based on cell type, tissue type, and species. In healthy cells, nuclear morphology is generally tightly regulated and maintained; however, dynamic changes in nuclear morphology are observed under certain conditions, for instance in early embryos and in some immune cells. Deviations in normal nuclear morphology are linked to numerous diseases, including most cancers and premature aging syndromes. Many regulators of nuclear morphology have been identified, encompassing both intranuclear, cytoplasmic, and extracellular factors. Of note, recent studies have converged on chromatin and chromatin-associated proteins as key determinants of nuclear morphology and dynamics. In this review we discuss how the chromatin landscape regulates nuclear morphology in both normal and diseased cellular states. Additionally, we highlight emerging technologies that promise to bridge critical gaps in our understanding of nuclear morphology, including new approaches to probe nuclear structure and the use of synthetic cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1634252"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658817","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":"Temporal dynamics of gene and protein signatures following volumetric muscle loss.","authors":"Ishita Jain, Beu P Oropeza, Caroline Hu, Gladys Chiang, Sree Aravindan, Renato Reyes, Daniel Yuhang Li, Paul Cheng, Ngan F Huang","doi":"10.3389/fcell.2025.1606609","DOIUrl":"10.3389/fcell.2025.1606609","url":null,"abstract":"<p><strong>Introduction: </strong>Volumetric muscle loss (VML) is characterized by permanent tissue impairment resulting from critically-sized muscle loss. We performed time-series transcriptomic and proteomic analyses to reveal key mediators of irreversible pathological remodeling after induction of VML in mice.</p><p><strong>Methods: </strong>The dynamics of gene and protein expression patterns were analyzed for up to 3 weeks after muscle injury.</p><p><strong>Results: </strong>RNA Sequencing revealed transcriptional patterns that show rapid upregulation or downregulation shortly after injury, among which a subset of genes failed to return to pre-injury levels within 3 weeks after VML. Time-series analysis revealed gene clusters with sustained upregulation after 3 weeks, including those associated with extracellular matrix remodeling and inflammation, whereas the gene clusters having sustained downregulation were associated with mitochondrial function and metabolism. We further identified <i>SPI1</i> and <i>SP1</i> as novel molecular mediators of the pathological remodeling process.</p><p><strong>Discussion: </strong>This work demonstrates the utility of time-series analysis to reveal dysregulated pathways in the setting of VML.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1606609"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12268354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658820","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":"Age-dependent integration of cortical progenitors transplanted at CSF-neurogenic niche interface.","authors":"Gretchen Greene, Nikorn Pothayee, Jahandar Jahanipour, Hyesoo Jie, Jung-Hwa Tao-Cheng, Emily Petrus, Dragan Maric, Alan P Koretsky","doi":"10.3389/fcell.2025.1577045","DOIUrl":"10.3389/fcell.2025.1577045","url":null,"abstract":"<p><p>There has been renewed interest in neural transplantation of cells and tissues for brain repair. Recent studies have demonstrated the ability of transplanted neural precursor cells and <i>in vitro</i> grown organoids to mature and locally integrate into host brain circuitry. Most studies have focused on how the transplant behaves and functions after the procedure, but the extent to which the host brain can properly innervate the transplant, particularly in the context of aging, is largely unexplored. Here we report that transplantation of rat embryonic cortical precursor cells into the cerebrospinal fluid-subventricular zone (CSF-SVZ) interface of adult rat brains generates a brain-like tissue (BLT) at an ectopic site. This model allows for the assessment of precursor cell development, cellular interactions, and graft-host connectivity as a function of host age. We found that the transplanted precursor cells initially proliferated, then differentiated, and developed into mature BLTs, which received supportive cellular components from the host including blood vessels, microglia, astrocytes, and oligodendrocytes. There was integration of the BLT into the host brain which occurred at all ages studied, suggesting that host age does not affect the maturation and integration of the precursor cell-derived BLT. Long-range axonal projections from the BLT into the host brain were robust throughout the different aged recipients. However, long-distance innervation originating from the host brain into the BLT significantly declined with age. This work demonstrates the feasibility and utility of integrating new neural tissue structures at ectopic sites into adult brain circuits to study host-transplant interactions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1577045"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658816","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":"PD-L1 expression predicts the efficacy of PD-1 blockade plus chemotherapy versus chemotherapy alone in treatment-naïve advanced or metastatic gastric cancer: a pooled analysis of reconstructed individual patient-level data from two randomized trials.","authors":"Wei Zhou, Zeng-Zhi Cai, Zhuolin Fan, Xu Zheng, Yu-Tong Chen","doi":"10.3389/fcell.2025.1636288","DOIUrl":"10.3389/fcell.2025.1636288","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy alone exhibits suboptimal efficacy in patients with treatment-naïve advanced gastric cancer (GC). Randomized controlled trials (RCTs) have demonstrated that combining Programmed Cell Death Protein-1 (PD-1) blockade with chemotherapy significantly improves overall survival (OS) compared to chemotherapy alone. However, the efficacy of PD-1 inhibitors in patients with low Programmed Cell Death-Ligand 1 (PD-L1) expression remains unclear.</p><p><strong>Methods: </strong>Electronic databases were searched for RCTs comparing PD-1/PD-L1 inhibitors plus chemotherapy to placebo plus chemotherapy or chemotherapy alone in treatment-naïve advanced gastric or gastroesophageal junction adenocarcinoma patients. Individual patient-level data (IPD) for overall survival (OS) and progression-free survival (PFS) were reconstructed. The KMSubtraction algorithm was employed to derive IPD for the PD-L1-low subgroup. Treatment effects in PD-L1-high and PD-L1-low subgroups were evaluated using Cox proportional hazards models with shared frailty to account for between-study heterogeneity. Interaction tests were performed to assess differences in treatment effects between these subgroups.</p><p><strong>Results: </strong>Nine RCTs were included in the qualitative analysis. A combined positive score (CPS) of 5 was selected as the cutoff for analysis, with CheckMate 649 and ORIENT-16 trials included. In the CPS<5 subgroup, OS (CheckMate 649: HR = 0.97, 95% CI 0.81-1.17, P = 0.758; ORIENT-16: HR = 0.94, 95% CI 0.68-1.31, P = 0.725) and PFS (CheckMate 649: HR = 0.95, 95% CI 0.79-1.14, P = 0.580; ORIENT-16: HR = 0.73, 95% CI 0.52-1.01, P = 0.055) did not significantly differ between patients receiving PD-1 blockade plus chemotherapy and those receiving chemotherapy alone. Pooled analysis of reconstructed OS IPD from CheckMate 649 and ORIENT-16 (N = 2,231) revealed that PD-1 blockade significantly improved OS in the CPS≥5 subgroup (HR = 0.69, 95% CI 0.60-0.79, P < 0.001), but not in the CPS<5 subgroup (HR = 0.96, 95% CI 0.82-1.13, P = 0.643). Interaction tests showed a significantly attenuated treatment effect on OS in the CPS<5 subgroup compared to the CPS≥5 subgroup (Pinteraction = 0.002). Similar findings were observed in the pooled analysis of PFS data (Pinteraction = 0.011).</p><p><strong>Conclusion: </strong>The addition of PD-1 inhibitors to first-line chemotherapy provides minimal benefit in patients with CPS<5. Therefore, PD-1 inhibitors should be individualized for this patient subset.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1636288"},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658818","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":"Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.","authors":"Weiqing Li, Tai Zhang","doi":"10.3389/fcell.2025.1620756","DOIUrl":"10.3389/fcell.2025.1620756","url":null,"abstract":"<p><p>Gastric cancer remains a significant global health challenge, representing the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related mortality worldwide. Understanding the pathogenesis of precancerous lesions is crucial for developing effective prevention and treatment strategies. This review provides a comprehensive analysis of animal models for gastric precancerous lesions, categorizing them into <i>Helicobacter</i> infection models, chemical carcinogen or diet-induced models, multifactorial induction models, chemical injury models, and genetically engineered mouse models. We evaluate the advantages and limitations of each model type, with particular focus on their ability to recapitulate the Correa cascade of human gastric carcinogenesis. While <i>Helicobacter</i> felis infection in C57BL/6 mice most closely mirrors the progression from chronic gastritis through metaplasia to dysplasia, these models primarily produce spasmolytic polypeptide-expressing metaplasia rather than true intestinal metaplasia, limiting translational relevance. Chemical carcinogen models reliably produce tumors but often bypass intermediate precancerous stages. Recent advances in genetic engineering, particularly stomach-specific inducible Cre recombinase systems targeting gastric progenitor cells, have yielded models that faithfully reproduce the spectrum of human gastric cancer subtypes with features of metastatic disease. We highlight the importance of standardized histopathological evaluation methodologies and discuss future research directions, including integration of advanced technologies such as single-cell RNA sequencing with existing animal models, development of organoid models, and investigation of interactions among genetic predisposition, <i>Helicobacter</i> infection, and environmental factors. This review provides a valuable reference for researchers investigating gastric precancerous lesions and offers insights for the development of more effective prevention and treatment strategies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1620756"},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648913","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}