BioFactors最新文献

{"title":"The Hidden Conductor: HDL–Gut Microbiome Interplay in the Pathophysiology of Inflammatory-Based Diseases","authors":"Anouar Hafiane,&nbsp;Robert S. Kiss,&nbsp;Elda Favari,&nbsp;Amedeo Amedei,&nbsp;Cinzia Parolini","doi":"10.1002/biof.70162","DOIUrl":"https://doi.org/10.1002/biof.70162","url":null,"abstract":"<div>\u0000 \u0000 <p>High-density lipoprotein (HDL) is a cholesterol transporter that plays a well-defined role in reverse cholesterol transport. In addition, HDL shows anti-inflammatory and immunomodulatory functions mainly due to its ability to decrease the cholesterol content in lipid rafts, thus strongly influencing the membrane fluidity and the right localization/functionality of membrane-associated proteins (i.e., receptors/ligands) and their signal transduction pathways. Diverse experimental and clinical studies support the existence of a dynamic and complex relationship between HDL functionality and the gut microbiome (GM), with relevant implications for the pathophysiology of many widespread inflammatory-based diseases, such as cardiovascular disease (CVD), inflammatory bowel disease (IBD), neurodegenerative disorders (NDDs) and cancer. Host factors (age, genes, dietary and lifestyle habits, medications) or environmental conditions may strongly negatively affect both the HDL system and the GM composition and function, promoting chronic low-grade inflammatory conditions that may exacerbate susceptibility to these human pathologies. Therefore, it can be hypothesized that the HDL-GM relationship may represent a novel therapeutic target to decrease the burden of these inflammatory-based pathologies. This review summarizes current data about the role of HDL and GM in the pathogenesis of CVD, IBD, NDDs and cancer, as well as findings that support the HDL-GM interplay as a crucial factor in the development of these relevant illnesses. Finally, we discuss the shortcomings of this relationship delineating the future directions to address them.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Single-Cell and Spatial Multi-Omics Reveal S100A12+ Neutrophil Reprogramming Across Oral Inflammatory States and Immunotherapy-Associated Perturbation","authors":"Chen Li,&nbsp;Qi Cai,&nbsp;Jingwen Cai,&nbsp;Xuanyi Ma,&nbsp;Zhizen Quan,&nbsp;Yu Chen,&nbsp;Wenhao Tao,&nbsp;Xu Han,&nbsp;Yibo Wei,&nbsp;Xiaogang Xu","doi":"10.1002/biof.70157","DOIUrl":"10.1002/biof.70157","url":null,"abstract":"<div>\u0000 \u0000 <p>Oral squamous cell carcinoma (OSCC) develops through a continuum of tissue states from chronic inflammation and potentially malignant lesions to invasive cancer, yet the dynamic remodeling of the oral immune microenvironment and its relevance to immunotherapy-associated inflammation remain poorly understood. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, murine immunotherapy datasets, and experimental validation to characterize immune and stromal alterations across healthy mucosa, periodontitis, leukoplakia, and OSCC. This integrated analysis revealed distinct oral immune microenvironment states and identified condition-associated neutrophil programs, including an S100A12-enriched inflammatory state, an S100A14-associated metabolic state in leukoplakia, and tumor-associated neutrophil states in OSCC. Spatial analyses and cell–cell communication modeling further nominated immune–stromal interaction networks involving S100A12⁺ neutrophils and fibroblast-associated inflammatory signaling. A machine-learning framework identified a nine-gene Neu_S100A12-associated signature that discriminated periodontitis-associated inflammatory states across two retrospective cohorts, with seven concordantly upregulated genes prioritized for biological validation. Multiplex immunofluorescence and an IFN-γ-primed OSCC inflammatory model provided experimental support for a TNF-associated inflammatory phenotype linked to the S100A12 program. Together, these findings establish a cross-sectional multi-omics framework for defining oral immune states and identify S100A12-associated neutrophil programs as candidate mediators of oral inflammation and immunotherapy-related immune perturbation, providing a foundation for future prospective and mechanistic studies.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Peptidome Characterization of Ladakh Himalayan Hard Cheese With Comparative Insights From Sikkim","authors":"Ashish Kumar Singh,&nbsp;Rounak Chourasia,&nbsp;Md Minhajul Abedin,&nbsp;Ashutosh Kumar Singh,&nbsp;Sudhir Pratap Singh,&nbsp;Amit Kumar Rai","doi":"10.1002/biof.70160","DOIUrl":"10.1002/biof.70160","url":null,"abstract":"<div>\u0000 \u0000 <p>Traditional fermented products of the Indian Himalayas are gaining attention due to their health benefits. Ladakh hard <i>chhurpi</i> (LHC) collected from different altitudes (2784–4523 m) was assessed for antioxidant and ACE inhibitory activities. The activity of LHC generally increased upon GI digestion. Peptidome analysis of GI-digested LHCs revealed varying peptide profiles and the presence of bioactive and multifunctional peptides. Comparative peptidome analysis of Ladakh (Western Himalaya) and Sikkim (Eastern Himalaya) cheese revealed 5 common peptides. Amino acid composition analysis revealed proline and leucine to be the most abundant in Ladakh and Sikkim cheese, respectively. The MPO and ACE inhibitory potential of several novel peptides were predicted. <i>VYPFPGPI</i> demonstrated high MPO binding affinity. <i>GGVSLPE</i> was predicted to have the best ACE inhibition potential. In vitro activity assessment revealed <i>VYPFPGPI</i> as a more potent ACE inhibitor (IC₅₀ of 215.5 ± 7.87 μM), while <i>GGVSLPE</i> showed higher MPO inhibitory activity (IC₅₀ of 0.84 ± 0.05 mM) between the two peptides. This is the first report on the LHC peptidome profile and comparative peptidome analysis of the hard cheese of Ladakh and Sikkim. The present study proposes bioactive peptides-enriched LHCs as a functional food of Ladakh with nutraceutical potential.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-Derived Collagen Peptides as Emerging Biofactors: Molecular Characteristics, Biological Mechanisms, and Potential Roles in Healthy Aging","authors":"Huijie Wu,&nbsp;Miao Dong,&nbsp;Shaotao Jiang,&nbsp;Lewei Tu,&nbsp;Xiaoyu Tao,&nbsp;Lixian Wu,&nbsp;Yan Ai,&nbsp;Quancai Sun,&nbsp;Ying Xiao,&nbsp;Ye Peng","doi":"10.1002/biof.70159","DOIUrl":"10.1002/biof.70159","url":null,"abstract":"<div>\u0000 \u0000 <p>Marine-derived collagen (MDC) represents a sustainable source of bioactive biomolecules derived from marine processing by-products, with emerging applications in molecular nutrition and healthy aging. Compared with mammalian collagen, MDC exhibits distinctive structural characteristics, including variable imino acid composition, reduced thermal stability, and enhanced enzymatic accessibility, which determine its physicochemical properties, processing behavior, and biological potential. These structural features also underpin the distinct functional roles of native collagen and collagen-derived peptides: intact MDC retains triple-helical architectures and extracellular matrix-interactive motifs that support cellular responses and tissue homeostasis, whereas hydrolyzed marine collagen peptides (MCPs) are orally administered bioactive peptides that can undergo gastrointestinal absorption and have been investigated for potential systemic health effects. This review summarizes current advances in the molecular characteristics, sustainable production, structural modification, and biological functions of MDC and MCPs, emphasizing the structure–function relationships that govern their nutritional and physiological effects. We discuss how extraction and processing strategies regulate collagen architecture, peptide generation, and bioactivity, and further examine the molecular mechanisms that have been proposed to underlie the antioxidant, anti-inflammatory, metabolic regulatory, and musculoskeletal protective effects of MCPs. Particular attention is given to aging-associated physiological decline, in which oxidative stress, chronic inflammation, and extracellular matrix deterioration contribute to impaired tissue homeostasis. Emerging experimental evidence suggests that marine collagen-derived bioactive peptides may modulate key signaling pathways, including Nrf2-mediated antioxidant responses, NF-κB-related inflammatory regulation, and pathways involved in connective tissue remodeling and metabolic balance. Finally, we highlight current challenges limiting the broader application of MDC-derived biofactors, including source variability, structural and compositional standardization, bioavailability characterization, and the need for well-designed human studies. By integrating marine sustainability, molecular structure, and biological function, MDC and its derived peptides may serve as promising food-derived biofactors with potential applications in supporting healthy aging and age-related health maintenance.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “HPV Infection Drives CXCL8+ Neutrophil-Mediated Immune Suppression in Cervical Cancer”","authors":"","doi":"10.1002/biof.70158","DOIUrl":"10.1002/biof.70158","url":null,"abstract":"<p>\u0000 <span>M. Liu</span>, <span>L. Zhang</span>, <span>Y. Fan</span>, et al., “ <span><i>HPV Infection Drives CXCL8</i>^<i>+</i> <i>Neutrophil-Mediated Immune Suppression in Cervical Cancer</i></span>,” <i>BioFactors</i> <span>52</span>, no. <span>4</span> (<span>2026</span>): e70131, https://doi.org/10.1002/biof.70131.\u0000 </p><p>In the originally published article, author Lina Zhang's affiliation was given incorrectly. The correct affiliation is shown below. The online version of this article has been updated.</p><p>We apologize for this error.</p><p>Incorrect:</p><p>Miaomiao Liu¹, Lina Zhang¹, Yanan Fan¹, Lina Han¹, Lei Tian¹, Lili Peng¹, Liya He¹, Qiaofang Li¹, Xiaolu Yan¹, Ting Shen²</p><p>¹Hebei General Hospital, Shijiazhuang, China</p><p>²Department of Oncology, Hebei Chest Hospital, Shijiazhuang, China</p><p>Miaomiao Liu, Lina Zhang and Yanan Fan contributed equally to this work.</p><p>Correct:</p><p>Miaomiao Liu¹, Lina Zhang², Yanan Fan¹, Lina Han¹, Lei Tian¹, Lili Peng¹, Liya He¹, Qiaofang Li¹, Xiaolu Yan¹, Ting Shen³</p><p>¹Hebei General Hospital, Shijiazhuang, China</p><p>² Radiotherapy Department Affiliated Hospital of Hebei University, Baoding, China</p><p>³Department of Oncology, Hebei Chest Hospital, Shijiazhuang, China</p><p>Miaomiao Liu and Lina Zhang contributed equally to this work.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FZD7 Shapes Mitochondrial Function and Oxidative Stress in Hepatocellular Carcinoma: A Potential Prognostic Biomarker","authors":"Peishu Huang,&nbsp;Fuqun Wei,&nbsp;Yiping Chen,&nbsp;Yuanmeng Yang","doi":"10.1002/biof.70156","DOIUrl":"10.1002/biof.70156","url":null,"abstract":"<p>Mitochondrial metabolism and oxidative stress (OS) play critical roles in the progression of hepatocellular carcinoma (HCC). However, reliable prognostic biomarkers for these processes remain unidentified. This study integrated bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to identify OS&amp;mitochondrial metabolism-related genes (OMRGs). A prognostic model was constructed using LASSO regression, followed by external validation. Associations of the model with clinicopathological features, tumor microenvironment (TME), immune functions, therapeutic response, and drug sensitivity were systematically explored. Finally, the relationships between key OMRGs and mitochondrial metabolism as well as OS were validated. A risk score based on five key OMRGs (LPCAT1, IMPDH1, RAMP3, FZD7, and B4GALT5) was established. Low OMRS was significantly associated with improved overall survival and identified as an independent prognostic factor. Two subtypes (C1/C2) were characterized based on the OMRGs: the C1 subtype exhibited poorer survival and epithelial-mesenchymal transition (EMT) enrichment, whereas the C2 subtype showed greater immune infiltration and sensitivity to immunotherapy. High OMRS was associated with higher predicted IC₅₀ values to oxaliplatin and cisplatin, while low OMRS indicated favorable responses to TACE, sorafenib, and immunotherapy. FZD7 knockdown increased reactive oxygen species (ROS) levels and reduced mitochondrial membrane potential in HCC cells. FZD7, a key gene among OMRGs, represent promising prognostic biomarkers and therapeutic targets in HCC.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Extracellular Matrix Synthesis–Related Responses Induced by Ubiquinol-10 Derivatives in Human Dermal Fibroblasts","authors":"Shotaro Goto,&nbsp;Masako Harada,&nbsp;Shuichi Setoguchi,&nbsp;Kazuhisa Matsunaga,&nbsp;Jiro Takata","doi":"10.1002/biof.70154","DOIUrl":"10.1002/biof.70154","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin aging is characterized by impaired extracellular matrix (ECM) synthesis and increased inflammatory signaling in dermal fibroblasts. Notably, ubiquinol-10 (UqH-10), the reduced form of coenzyme Q10 (ubiquinone-10, Uq-10), supports mitochondrial function and reduces oxidative stress, but its dermal levels decrease with aging. The topical efficacy of UqH-10 is limited by its physicochemical properties, including oxidative instability, photo instability, and phototoxicity. This study aimed to evaluate the anti-aging potential of esterified UqH-10 derivatives—UqH 1,4-bis-hemi-succinate (UqH-SUC) and UqH 1,4-bis-hemi-glutarate (UqH-GLUT)—in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were treated with Uq-10, UqH-10, or their derivatives (100 μM) for 48 h. Intracellular Uq-10 and UqH-derivatives were quantified by LC–MS/MS, while ATP levels and viability were measured using luminescence- and fluorescence-based assays. Gene and protein expression of ECM components, matrix metalloproteinases (MMP1, MMP3), and SASP markers (IL6, IL8, p21) were analyzed by qPCR, ELISA, western blotting, and immunofluorescence. Additional experiments were conducted in the presence of an ascorbic acid derivative to evaluate pro-COL1A1 production. We found that UqH-SUC markedly increased intracellular Uq-10 and UqH-10 (2.1-fold vs. Uq-10; 8.3-fold vs. UqH-10), enhanced ATP production, suppressed SASP factors, and upregulated ECM components including COL1A1, elastin, and hyaluronic acid. Despite its minimal conversion to UqH-10, UqH-GLUT accumulated intracellularly, reduced SASP expression, and downregulated MMPs. Co-treatment with UqH-SUC and phosphorylated ascorbic acid derivatives significantly enhanced extracellular COL1A1 secretion while lowering intracellular retention. Moreover, esterified UqH-10 derivatives, particularly UqH-SUC, enhance mitochondrial function, modulate fibroblast senescence, and stimulate ECM synthesis. Moreover, their combination with ascorbic acid derivatives provides a promising strategy for skin anti-aging intervention.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KPNβ1 and NKCC1 Modulators as Key Players in HCC: Possible Interventions in Cell Cycle Arrest and Apoptosis","authors":"Shimaa A. Abass,&nbsp;Doaa H. Elhasanein,&nbsp;Ramadan A. Eldomany,&nbsp;Sherin Zakaria","doi":"10.1002/biof.70155","DOIUrl":"10.1002/biof.70155","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) remains a major challenge threatening global health. It has a high incidence with poor prognosis, and its response to current conventional therapies is not satisfactory, so we need to explore new effective therapies to address this problem. Targeted therapy represents a promising approach, but the therapeutic efficacy of targeting ion transporters and nuclear transport proteins, such as Na+/K+/2Cl− cotransporter 1 (NKCC1) and Karyopherin β1 (KPNβ1), remains poorly investigated. This study aims to assess the therapeutic efficacy of targeting NKCC1 and KPNβ1 individually and in combination. We also explored the roles of these transporters in tumor cell proliferation and HCC progression. To achieve this aim, an HCC rat model was used, induced by diethylnitrosamine and phenobarbital. The evaluation included histopathological examination and assessment of liver function biomarkers (alanine aminotransferase and aspartate aminotransferase), cell cycle regulators (Cyclin D1, p21, E2F1), proliferation (Ki-67), apoptosis (Caspase-3), and expression of NKCC1 and KPNβ1. This study revealed that NKCC1 and KPNβ1 were upregulated in the HCC group. This increase was associated with increased proliferation and suppressed apoptosis. Targeting these proteins, particularly in combination, significantly improved liver function. It also induced cell cycle arrest, reduced proliferative markers, and enhanced apoptosis. These findings indicate that NKCC1 and KPNβ1 could serve as possible therapeutic targets in HCC treatment.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PTTG1/AURKA Axis Drives Acquired Anlotinib Resistance in Non-Small Cell Lung Cancer by Remodeling the Tumor Immune Microenvironment","authors":"Kaiyuan Hui,&nbsp;Yonghua Tan,&nbsp;Jiawei Song,&nbsp;Chenxi Hu,&nbsp;Shuo Wu,&nbsp;Wen Sun,&nbsp;Liying Song,&nbsp;Xiaodong Jiang","doi":"10.1002/biof.70153","DOIUrl":"10.1002/biof.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>PTTG1 has been implicated in tumor progression and drug resistance, but its role in acquired anlotinib resistance in non-small cell lung cancer (NSCLC) remains unclear. This study investigated whether PTTG1 contributes to resistance and immune remodeling in NSCLC. We analyzed peripheral blood from NSCLC patients collected before treatment, during response, and after acquired resistance to define clinical changes associated with anlotinib failure. Anlotinib-resistant A549/AL and NCI-H1975/AL cell models were established and subjected to lentiviral shRNA-mediated PTTG1 silencing to assess tumor-intrinsic functions and drug sensitivity. Tumor cell proliferation, migration, invasion, and molecular changes were evaluated using CCK-8, EdU, Transwell, reverse transcription quantitative polymerase chain reaction, Western blotting, immunofluorescence, immunohistochemistry, co-immunoprecipitation, STRING analysis, and humanized mouse models. Immune remodeling was assessed by flow cytometry in PBMC co-culture and tumor samples to examine T-cell subsets and cytotoxic effector activity. PTTG1 was upregulated in resistant clinical samples and resistant NSCLC cell models. Silencing PTTG1 suppressed proliferation, migration, invasion, epithelial-mesenchymal transition, tumor growth and metastasis in vivo, with enhanced anlotinib efficacy observed in subcutaneous xenografts. PTTG1 knockdown reprogrammed the tumor immune microenvironment (experimental models) toward an activated cytotoxic state, characterized by increased CD8+ T-cell infiltration and enhanced cytotoxic effector activity, with reduction of immune checkpoint-associated suppression. Mechanistically, STRING analysis and co-immunoprecipitation identified AURKA as a direct PTTG1-interacting protein, and AURKA overexpression reversed the immune-activating effects of PTTG1 depletion. In conclusion, PTTG1 promotes acquired anlotinib resistance in NSCLC by coupling malignant progression with immune suppression via the PTTG1-AURKA axis. Targeting PTTG1 may be a strategy to overcome resistance and restore anti-tumor immunity.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clear Cell Carcinoma With Enteroblast-Like Differentiation Involving Multiple Gynecologic Sites: An Integrated Clinicopathologic, Whole-Exome, and Transcriptomic Analysis","authors":"Ying Zhang,&nbsp;Min Sun,&nbsp;Chen Qian,&nbsp;Ziyi Guo,&nbsp;Xue Xu,&nbsp;Xiangshan Fan","doi":"10.1002/biof.70152","DOIUrl":"https://doi.org/10.1002/biof.70152","url":null,"abstract":"<div>\u0000 \u0000 <p>Clear cell carcinoma with enteroblastic differentiation arising in the female genital tract is exceptionally rare, and its pathogenesis, diagnostic features, and therapeutic implications remain poorly understood. We report a rare case in a 67-year-old woman with tumor involvement of the cervix, uterine cavity, fallopian tubes, and ovaries, and highlight the value of multi-site sequencing for resolving tumor origin and biological heterogeneity. Histologically, the tumor exhibited a fetal intestinal-like morphology with glycogen-rich clear cytoplasm. Immunohistochemistry revealed positive staining for HNF1β, with variable immunoreactivity for Glypican-3 and SALL4. Multi-site whole-exome sequencing revealed marked inter-lesional genomic heterogeneity, divergent clonal evolution, and a molecular phylogenetic pattern supporting the fallopian tube as the most likely primary site. RNA sequencing further demonstrated a more immunogenic microenvironment in the fallopian tube lesion, characterized by increased infiltration of CD4⁺ T cells and B cells and a higher immunophenoscore, suggesting potential sensitivity to immunotherapy. Comparison with previously reported cases also helped define immunophenotypic features of diagnostic relevance. Collectively, this case underscores the value of integrating clinicopathologic evaluation with multi-site whole-exome and transcriptomic sequencing to refine diagnosis, infer tumor origin, and identify potential therapeutic opportunities in this rare gynecologic tumor subtype.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 5","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}