BioFactors最新文献

{"title":"Growth Differentiation Factor 15 (GDF15) Protects Against Sepsis-Associated Acute Kidney Injury via Suppression of TLR4-MyD88-NF-κB Signaling and Ferroptosis","authors":"Chengyi Yang,&nbsp;Le Zhao,&nbsp;Jia Di,&nbsp;Qiangyan Hu","doi":"10.1002/biof.70138","DOIUrl":"10.1002/biof.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis-associated acute kidney injury (SAKI) lacks mechanism-based therapies, with upstream ferroptosis regulators undefined. This study investigated growth differentiation factor 15 (GDF15) as a suppressor of TLR4-MyD88-NF-κB signaling and associated ferroptosis. Differential GDF15 expression was identified by integrated analysis of three GEO datasets (GSE232404, GSE30718, GSE44925) and validated in SAKI patient kidney tissue (<i>n</i> = 30 vs. controls <i>n</i> = 25) and in kidneys from cecal ligation and puncture (CLP) mice. CLP mice received recombinant GDF15 (rmGDF15) (50 ng/kg ip); renal function (Scr/BUN), histology, kidney injury molecule-1 (KIM-1), serum TNF-α/IL-1β/IL-6 (ELISA), and 7-day survival were assessed. Oxidative stress/ferroptosis was quantified by DCFH-DA ROS imaging and kits (MDA, GSH, SOD, NADPH, Fe, GPX4 activity); TLR4-MyD88-NF-κB by qRT-PCR, Western blot, and Immunohistochemistry. LPS (1 μg/mL, 48 h)-stimulated HK-2 cells underwent shGDF15 lentiviral knockdown (puromycin 2 μg/mL) ± TAK242 (1 μM); viability (CCK-8), apoptosis (Annexin V/PI flow), cytokines (ELISA/qRT-PCR), ROS, ferroptosis markers, and pathway activation were evaluated. GDF15 was upregulated in SAKI datasets, patient kidney tissue, and CLP kidneys. GDF15 supplementation improved survival, lowered Scr/BUN and KIM-1, attenuated tubular injury, and reduced systemic proinflammatory cytokines. It decreased renal ROS, MDA and Fe while restoring GSH, SOD, NADPH, GPX4 activity, and SLC7A11 expression, and suppressed TLR4-MyD88-NF-κB signaling. In HK-2 cells, GDF15 silencing aggravated LPS-induced loss of viability, apoptosis, cytokine release, oxidative stress, and ferroptosis markers, all reversed by TAK242. In conclusion, GDF15 is a stress-inducible renoprotective factor that suppresses TLR4 signaling, ferroptosis markers, and inflammation in SAKI, suggesting exogenous administration as a promising therapeutic strategy.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677059","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":"Adenosine Receptor 3 Antagonism Suppresses Adipogenesis via the EREG-EGFR-Leptin Axis in Multipotent Cells","authors":"Chia-Huei Lee,&nbsp;Kuo-Yun Tseng,&nbsp;Feng-Huei Lin,&nbsp;Hung-Ming Wu,&nbsp;Shankung Lin","doi":"10.1002/biof.70140","DOIUrl":"10.1002/biof.70140","url":null,"abstract":"<div>\u0000 \u0000 <p>The role of adenosine receptor 3 (AR3) signaling in adipogenesis remains unclear. Here, we show that AR3 antagonism by MRS1220 inhibited adipogenic differentiation in both C3H10T1/2 and 3T3-L1 cells, as evidenced by reduced lipid accumulation in both models and suppressed PPARγ2 expression in C3H10T1/2 cells. Transcriptomic profiling and pathway analysis performed in C3H10T1/2 cells suggested that the <i>Ereg</i> gene, which encodes epiregulin (EREG), is a potential target of MRS1220 mediated adipogenesis inhibition. Mechanistically, MRS1220 induced EREG expression, leading to EGFR activation and leptin upregulation, which were critical for its anti-adipogenic effect. Recombinant EREG mimicked, and EREG neutralization reversed, MRS1220's inhibitory activity. EGFR inhibition abolished MRS1220-induced leptin expression and restored adipogenesis. Notably, AR3 knockdown abrogated MRS1220's effects on EREG induction, EGFR phosphorylation, leptin induction, and lipid accumulation. In contrast, the AR3 agonist CF101 enhanced adipogenesis independent of the EREG-EGFR-leptin axis. These findings establish AR3 as a key regulator of adipogenic differentiation and uncover an AR3-EREG-EGFR-leptin signaling cascade as a mechanism by which AR3 antagonism inhibits adipogenesis. Targeting AR3 may offer a novel strategy to modulate adipose tissue formation in metabolic diseases.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663072","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":"Pulp Callus Extract From Malus domestica var. Mela Rosa Marchigiana Preserves Intestinal Barrier Integrity and Confers Neuroprotection in a Gut–Brain Axis Co-Culture Model","authors":"Alessandro Nicois,&nbsp;Daniele Fraternale,&nbsp;Francesco Palma,&nbsp;Brenda Marfella,&nbsp;Giuditta Fiorella Schiavano,&nbsp;Mariastella Colomba,&nbsp;Armando Gregorini,&nbsp;Barbara Di Giacomo,&nbsp;Luigia Cristino,&nbsp;Vincenzo Di Marzo,&nbsp;Maria Cristina Albertini,&nbsp;Letizia Palomba","doi":"10.1002/biof.70139","DOIUrl":"https://doi.org/10.1002/biof.70139","url":null,"abstract":"<p>The gut–brain axis is a key target in neuroinflammatory disorders. We investigated the protective effects of Mela Rosa Marchigiana pulp callus extract (MRME), a phytocomplex with a unique triterpenic profile. Using a validated transwell co-culture model of the intestinal-neural interface, differentiated Caco-2 cells formed a polarized epithelial barrier (apical), while BV2 microglia or SH-SY5Y neurons were seeded in the basolateral compartment. Apical MRME pretreatment preserved Caco-2 barrier integrity against lipopolysaccharide or dextran sodium sulfate-induced damage. MRME maintained occludin integrity and transepithelial electrical resistance (TEER), effectively neutralizing “leaky gut”-like conditions. By stabilizing the barrier, MRME exerted indirect neuroprotection since high-throughput live-cell imaging revealed dose-dependent reductions in reactive oxygen species generation and apoptosis (caspase-3/7 activation) in both BV2 and SH-SY5Y cells. MRME demonstrated a microbiologically neutral profile, exerting no inhibitory effects on either pathogenic or probiotic strains up to 10,000 μg/mL. MRME provides dual protection by strengthening the intestinal barrier and shielding the neural environment from systemic inflammation through host cellular modulation rather than microbial interference. These findings suggest MRME as a promising nutraceutical candidate for gut–brain axis dysregulation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647929","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":"A Multi-Omics and Single-Cell Framework Identifies ITGA1 as a Candidate Predictive Biomarker of Neoadjuvant Chemotherapy Response in Epithelial Ovarian Cancer","authors":"Xue Xu,&nbsp;Ruxue Yang,&nbsp;Lutong Fang,&nbsp;Min Sun,&nbsp;Ying Ma,&nbsp;Ying Zhang,&nbsp;Chenxin Wu","doi":"10.1002/biof.70135","DOIUrl":"10.1002/biof.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>Reliable biomarkers that predict therapeutic response remain a major unmet need in epithelial ovarian cancer (EOC), particularly for patients receiving neoadjuvant chemotherapy (NACT). Although high-throughput multi-omics technologies have accelerated biomarker discovery, the translation of candidate markers into clinically actionable predictors remains limited. Here, we developed an integrative multi-omics framework combining single-cell RNA sequencing, bulk transcriptomic profiling, and machine-learning-based modeling to identify biomarkers associated with chemotherapy response in EOC. Single-cell analyses were used to delineate cellular heterogeneity and intercellular communication landscapes before and after NACT, while bulk cohorts were leveraged to validate response-associated molecular signatures. Network-based and pathway analyses were applied to prioritize functionally relevant candidates. We identified integrin subunit alpha 1 (ITGA1) as a response-associated candidate with notable discriminatory performance for chemotherapy response and functional relevance in cisplatin-resistant ovarian cancer models. ITGA1-related signatures stratified patients by therapeutic response and were associated with immune and stress-response pathways, extracellular matrix signaling, and altered cell–cell communication patterns. Functional experiments showed that ITGA1 knockdown restored cisplatin sensitivity and suppressed clonogenic survival, migration, adhesion, and apoptosis evasion in resistant ovarian cancer cells. Together, our study supports ITGA1 as a response-discriminatory and functionally relevant biomarker candidate for chemotherapy response in EOC and highlights the value of integrating single-cell and bulk multi-omics data with machine-learning approaches. These findings provide a translational framework for patient stratification and experimental prioritization in ovarian cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454328","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":"A Di-Rhamnolipid (Rha2-C10-C10) Inhibits Colorectal Cancer Motility and Immune Evasion Through AKT-Associated Signaling and PD-L1 Regulation","authors":"Sultan Pulat,&nbsp;Prima F. Hillman,&nbsp;Jaeyoung Ko,&nbsp;Sang-Jip Nam,&nbsp;Hangun Kim","doi":"10.1002/biof.70129","DOIUrl":"10.1002/biof.70129","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) progression is driven by metastatic potential, metabolic reprogramming, and immune evasion. In this study, we investigated the effects of a di-rhamnolipid, Rha₂-C₁₀-C₁₀ (<b>1</b>), on CRC cell motility, energy metabolism, and immune-related signaling. Compound <b>1</b> exhibited minimal cytotoxicity in AGS, A549, and MDA-MB-231 cells, while modestly reducing viability in Caco2 cells at higher concentrations. Notably, it significantly suppressed invasion and migration, with the most pronounced effects observed in Caco2 cells. These effects were associated with downregulation of mesenchymal markers, including N-cadherin and transcription factors Snail and Slug, as well as matrix metalloproteinases (MMP2, MMP3, and MMP9), accompanied by increased TIMP2 expression. In addition, compound <b>1</b> attenuated metabolic activity by reducing the expression of key glycolytic regulators, including GLUT1, LDHA, and HK2. It also suppressed immune evasion–related factors such as PD-L1, IDO1, IDO2, and Galectin. Mechanistic investigations using BaP and the AKT inhibitor MK2206 suggest that the effects of compound <b>1</b> involve modulation of AKT-associated signaling while also engaging additional regulatory pathways. Collectively, these findings demonstrate that compound <b>1</b> suppresses colorectal cancer cell motility, metabolic activity, and immune evasion, highlighting its potential as a natural compound targeting multiple tumor-promoting processes.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410274","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":"HPV Infection Drives CXCL8+ Neutrophil-Mediated Immune Suppression in Cervical Cancer","authors":"Miaomiao Liu,&nbsp;Lina Zhang,&nbsp;Yanan Fan,&nbsp;Lina Han,&nbsp;Lei Tian,&nbsp;Lili Peng,&nbsp;Liya He,&nbsp;Qiaofang Li,&nbsp;Xiaolu Yan,&nbsp;Ting Shen","doi":"10.1002/biof.70131","DOIUrl":"10.1002/biof.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Persistent HPV infection is a major risk factor for cervical cancer, but the immune mechanisms behind HPV-induced tumor progression are not fully understood. Neutrophils may play a key role in immune remodeling and evasion within the HPV-infected tumor microenvironment. We integrated 31 cervical samples (including HPV-infected and non-infected normal, tumor, and HSIL tissues) to construct a single-cell atlas of 141,785 cells. Neutrophil heterogeneity, cell–cell communication, and immunosuppressive programs were systematically analyzed. Transcriptomic findings were validated via immunohistochemistry, immunofluorescence, and Mendelian randomization (MR). HPV infection dramatically remodeled the immune landscape, inducing robust neutrophil and plasma cell infiltration while reducing T cell abundance. Neutrophils in HPV+ tissues were terminally differentiated and displayed a distinct CXCL8⁺ phenotype. These CXCL8⁺ neutrophils were identified as late-stage, transcriptionally defined low-plasticity state enriched with immunosuppressive genes (e.g., SPP1, VEGFA). They exhibited enhanced interactions with T cell subsets, particularly regulatory and cytotoxic T cells, via ligands like CXCL16 and APOE, suggesting direct immunosuppressive crosstalk. MR analysis indicated a causal role for CXCL8 in cervical cancer, and spatial protein assays confirmed elevated CXCL8 and its receptor CSF3R in HPV+ tumors. HPV infection expands immunosuppressive CXCL8⁺ neutrophils that modulate T cell activity and promote immune escape. CXCL8 is identified as a causal factor and potential therapeutic target in HPV-driven cervical cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403289","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":"Caenorhabditis elegans and Drosophila melanogaster as Model Organisms in Biofactor Research","authors":"Kai Lüersen,&nbsp;Thomas Roeder,&nbsp;Gerald Rimbach","doi":"10.1002/biof.70127","DOIUrl":"10.1002/biof.70127","url":null,"abstract":"<p>Model organisms play a central role in advancing our understanding of human nutrition and physiology. This narrative review highlights the unique advantages of the invertebrate models <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i> for studying biofactors—diet-derived compounds that modulate biological functions. Both models offer powerful genetic toolkits, short life cycles, and cost-effective maintenance, enabling high-throughput and mechanistic investigations. Particular emphasis is placed on the availability of chemically defined diets, which allow precise manipulation of nutrient and biofactor composition. These features make <i>C. elegans</i> and <i>D. melanogaster</i> invaluable systems for dissecting the essentiality, bioavailability, and physiological impact of individual biofactors as illustrated by selected recent studies. Being ethically less problematic substitutes for mammalian models, both invertebrate models offer the possibility of closing the gap that often exists between in vitro and cell culture studies on the one hand and in vivo evaluation in animal experiments in laboratory rodents on the other. By integrating these model systems into experimental research, we can gain critical insights into biofactor-gene interactions and the molecular mechanisms underlying their health-promoting properties.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395727","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":"Integrative Multi-Omics Analysis Reveals the Tumor-Suppressive and Immunoregulatory Roles of SEMA5B in Prostate Cancer","authors":"Zhiguo Fan,&nbsp;Yihaoyun Lou,&nbsp;Xuan Zhou,&nbsp;Guang Liu,&nbsp;Xiaomin Zhang,&nbsp;Yuanjie Tang,&nbsp;Zhen Zhu,&nbsp;Shancheng Ren,&nbsp;Yifan Chang","doi":"10.1002/biof.70133","DOIUrl":"10.1002/biof.70133","url":null,"abstract":"<p>SEMA5B plays an important role in the maintenance of neural development and is highly environment dependent in tumorigenesis. The roles of SEMA5B in prostate cancer remain underexplored. This study investigates SEMA5B's functions in prostate cancer, revealing its role as a tumor suppressor transcriptionally regulated by androgen receptor and uncovering novel biomarkers and potential immunotherapeutic mechanisms. We analyzed SEMA5B's expression in cancer and its spatial association with cells in the tumor microenvironment using single-cell transcriptome sequencing datasets and spatial transcriptome sequencing samples. Using bulk RNA-seq data, we analyzed the immune infiltration of SEMA5B in prostate cancer. The association of SEMA5B with androgen receptor signaling and with metabolic pathways was evaluated by transcriptome and enrichment analysis. The phenotypes, cell cycle, apoptosis, and mitochondrial metabolic function of prostate cancer cell lines were further evaluated. SEMA5B regulation by androgen receptor was examined by gene knockdown, androgen/enzalutamide treatment, and epigenomics. Finally, the effect of SEMA5B on prostate cancer in vivo was detected by tumor xenograft model. Pan-cancer single-cell analysis revealed that SEMA5B's expression showed significant tumor type specificity and spatially correlated with immune cell infiltration. SEMA5B is associated with abundant lymphocyte and immune-inflammatory microenvironment in prostate cancer. SEMA5B overexpression inhibited tumor cell proliferation, migration, and invasion. Moreover, high SEMA5B is associated with oxidative phosphorylation and low glycolytic profile. SEMA5B expression is positively correlated with androgen receptor. Androgen receptor inhibition and androgen stimulation affected the expression of SEMA5B. ChIP confirmed the binding of androgen receptor to the SEMA5B promoter. Finally, SEMA5B was verified to induce cell cycle arrest and apoptosis and reduce tumor growth. SEMA5B inhibits tumor malignant phenotype and is associated with immune-inflammatory tumor microenvironment. SEMA5B can regulate mitochondrial oxidative metabolism and induce cell cycle arrest and cell apoptosis, inhibiting the growth of prostate cancer.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381410","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":"Alpinia zerumbet-Derived Extracellular Vesicles Protect Against UVB-Induced Photoaging by Enhancing Mitochondrial Bioenergetics and Skin Barrier Function","authors":"Mo-Rong Xu,&nbsp;Hui-Chun Wang,&nbsp;Meng-Shiou Lee,&nbsp;Sheng-Yang Wang","doi":"10.1002/biof.70134","DOIUrl":"10.1002/biof.70134","url":null,"abstract":"<p>Ultraviolet B (UVB) radiation is a major cause of skin photoaging by oxidative stress, mitochondrial dysfunction, and barrier disruption. Plant-derived extracellular vesicles (PDEVs) have emerged as promising bioactive nanocarriers, but their roles in mitochondrial regulation and skin barrier homeostasis remain unclear. This study aimed to investigate the protective effects of extracellular vesicles derived from <i>Alpinia zerumbet</i> leaves (AZEVs) against UVB-induced photoaging in HaCaT keratinocytes. The results indicated that AZEVs exhibited typical extracellular vesicle characteristics, with an average size of 150 nm and a negative surface charge. Functionally, AZEVs significantly enhanced cell viability in UVB-exposed HaCaT cells, reduced ROS accumulation, and restored mitochondrial membrane potential and ATP production. Moreover, AZEVs upregulated mitochondrial biogenesis-related signaling pathway proteins (SIRT1, PGC-1<i>α</i>, Nrf2, and <i>p</i>-AMPK/AMPK) and TJ protein expression (ZO-1, occludin, and claudin-3), preserving barrier integrity and promoting wound healing. In addition, AZEVs are enriched in conserved miRNAs (miR166, miR159, and miR156) and a novel miRNA (novel_1), with predicted targets involved in redox regulation and energy metabolism. In summary, AZEVs protect keratinocytes against UVB-induced damage by enhancing mitochondrial function, reducing oxidative stress, and preserving skin barrier integrity. These findings highlight AZEVs as a promising natural nanoplatform for anti-photoaging and skin repair applications.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381455","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":"Dauriporphine Inhibits the Proliferation, Migration, Angiogenesis, and Glycolysis in Lung Cancer Cells by Repressing PGK1 Expression via CEBPA","authors":"Pengxiao Hou,&nbsp;Zhizhong Liang,&nbsp;Qian Wu","doi":"10.1002/biof.70125","DOIUrl":"10.1002/biof.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>Many anti-cancer agents with therapeutic potential have been discovered in traditional Chinese medicine. Dauriporphine is an alkaloid extracted from <i>Menispermum dauricum DC.</i>, demonstrating anti-cancer properties. However, the precise role of dauriporphine in the treatment of lung cancer and its underlying biological mechanism remains unclear. Dauriporphine addition resulted in reduced proliferation, migration, angiogenesis, and glycolysis in A549 and H1299 cells. Phosphoglycerate kinase 1 (PGK1) was identified as the candidate gene involved in glycolysis and dauriporphine after prediction using public datasets. Dauriporphine administration decreased PGK1 expression, whereas PGK1 overexpression markedly abolished the suppressive effects of dauriporphine. The CCAAT/enhancer binding protein A (CEBPA) was predicted to be the transcription factor of PGK1 using the online QIAGEN. The binding between CEBPA and PGK1 promoter was predicted and verified using Jaspar algorithm and Human TFDB, as well as chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, and cellular thermal shift assay (CETSA). CEBPA silencing could repress tumor cell malignant behaviors, which could be partially restored by PGK1 overexpression. Moreover, the upregulation of CEBPA diminished the anti-tumor efficacy of dauriporphine. Furthermore, dauriporphine treatment suppressed tumor growth by regulating the CEBPA/PGK1 pathway in nude mice. Overall, the study demonstrated that dauriporphine inhibited proliferation, migration, angiogenesis, and glycolysis in lung cancer cells via the CEBPA/PGK1 pathway, providing a potentially effective therapeutic strategy for lung cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366667","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}