BioFactors最新文献

{"title":"HCC-Derived Alpha-Fetoprotein Impairs Bone Regeneration by Impairing Autophagic Flux and Promoting Runx2 Degradation in Osteoblasts","authors":"Hyung-Mun Yun,&nbsp;Kyung-Ran Park","doi":"10.1002/biof.70147","DOIUrl":"10.1002/biof.70147","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is frequently complicated by bone metastasis, leading to severe skeletal-related events. While alpha-fetoprotein (AFP) is the gold-standard biomarker for HCC diagnosis, its functional role as a systemic or paracrine mediator in the bone metastatic microenvironment remains largely unexplored. In the present study, we investigated whether HCC-secreted AFP impairs bone formation by disrupting autophagic flux, the glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway, and Runt-related transcription factor 2 (Runx2) stability in osteoblasts. Our results showed that AFP dose-dependently inhibited osteoblast differentiation and mineralization. Mechanistically, AFP impaired autophagic flux, resulting in reduced phosphorylated GSK3β (p-GSK3β) and β-catenin levels, which were accompanied by decreased Runx2 protein expression. Pharmacological activation of autophagy with rapamycin effectively reversed these AFP-induced changes, restoring GSK3β/β-catenin signaling and Runx2 expression. Furthermore, using an ex vivo mouse calvarial defect model, we found that HepG2-derived AFP markedly impaired new bone regeneration and reduced the numbers of osteoblasts and osteocytes. Importantly, these effects were significantly attenuated by AFP silencing in HepG2 cells. Collectively, our findings identify HCC-derived AFP as a potential mediator of bone impairment rather than solely a diagnostic biomarker. Targeting AFP-mediated impairment of autophagic flux may represent a promising therapeutic strategy for mitigating skeletal complications and restoring bone homeostasis in patients with bone-metastatic HCC.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807908","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":"Machine Learning Identifies SCO2 as a Metabolic Reprogramming Gene Promoting Lipid Accumulation in MAFLD","authors":"Along Li,&nbsp;Ronglin Xu,&nbsp;Liangliang Zhang,&nbsp;Xinjian Xu,&nbsp;Longfei Dai,&nbsp;Zhen Zhang","doi":"10.1002/biof.70144","DOIUrl":"https://doi.org/10.1002/biof.70144","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease characterized by metabolic dysregulation, inflammation, and fibrosis. Metabolic reprogramming is increasingly recognized as a key molecular driver of MAFLD progression; however, systematic identification of the genes involved remains limited. This study aimed to identify key metabolism reprogramming genes (KMRGs) associated with MAFLD using multi-cohort bioinformatics analyses and machine learning, and to validate their expression patterns and potential roles experimentally. Six MAFLD-related liver transcriptomic datasets were downloaded from the GEO database. GSE135251 and GSE126848 were merged to form the training cohort, whereas the remaining four datasets served as external validation cohorts. Differentially expressed genes (DEGs) were identified and intersected with metabolism reprogramming genes (MRGs) to obtain KMRGs. Functional enrichment analysis, disease association analysis, GeneMANIA network analysis, external validation, immune infiltration analysis, inflammation- and lipid metabolism/fibrosis-related analyses, and consensus clustering were subsequently performed. Machine learning models were then constructed, and SHapley Additive exPlanations (SHAP) analysis was used to prioritize key genes. Finally, the selected gene was experimentally validated using clinical liver tissue samples, free fatty acid (FFA)-induced steatosis models in AML12 and HepG2 cells, qRT-PCR, Western blotting, and Oil Red O staining. Ten KMRGs closely associated with MAFLD were identified. Functional enrichment analysis showed that these genes were mainly involved in PPAR signaling, epigenetic regulation, and FOXO-mediated oxidative stress and metabolic transcriptional processes. A transcriptome-based classification model for MAFLD was constructed using the Naive Bayes machine learning algorithm, and SHAP analysis identified SCO2 as a feature with relatively high importance in model prediction. External validation demonstrated that KMRGs exhibited abnormal expression patterns, diagnostic potential, and correlations with NAFLD activity score (NAS) across different cohorts. Further analyses showed that KMRGs were closely associated with immune microenvironment remodeling, inflammatory responses, lipid metabolic dysregulation, and fibrosis in MAFLD, and could define molecular subtypes with distinct pathological features. Experimental validation showed that SCO2 was highly expressed in clinical MAFLD samples and in FFA-induced in vitro steatosis models. Functional assays further indicated that SCO2 modulated FFA-induced lipid accumulation in vitro. KMRGs are closely associated with the presence and pathological activity of MAFLD. Among them, SCO2 showed high feature importance in machine learning analyses and was associated with FFA-induced lipid accumulation in vitro, suggesting that it is a candidate molecule for further mechanistic investigat","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784376","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":"miR-200a-3p Targets and Downregulates CDC25B Expression to Inhibit the Progression of Hepatocellular Carcinoma","authors":"Zixiang Huang,&nbsp;Xi Yu","doi":"10.1002/biof.70143","DOIUrl":"10.1002/biof.70143","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer originates from the uncontrolled proliferation of normal cells. Previous studies have demonstrated that CDC25B, a cell cycle-regulating phosphatase, is overexpressed in various tumors, including hepatocellular carcinoma, and its expression level may serve as a prognostic biomarker. The present study investigated the upstream miRNA regulators of CDC25B and demonstrated that their interactions can inhibit hepatocellular carcinoma progression. Here, stable hepatocellular carcinoma cell lines overexpressing or knocking down CDC25B were established using lentiviral vectors. The effects of CDC25B expression on the invasive phenotype of hepatocellular carcinoma cells were analyzed using plate cloning, scratch assays, and Transwell assays, and a subcutaneous tumor xenograft model in mice was established to evaluate the impact of CDC25B on tumor growth in vivo. Furthermore, dual-luciferase reporter assays were used to validate the targeted regulatory relationship between miR-200a-3p and CDC25B, while miR-200a-3p mimics and inhibitors were employed to elucidate the specific downstream mechanisms. We found that high expression of CDC25B significantly enhanced the epithelial–mesenchymal transition process, thereby accelerating the proliferation, invasion, and migration of hepatocellular carcinoma cells, whereas CDC25B knockdown exerted the opposite effects. In vivo tumorigenicity experiments in nude mice confirmed that overexpression of CDC25B promoted tumor growth. In addition, the dual-luciferase reporter assay confirmed that miR-200a-3p specifically targets and downregulates CDC25B expression, thereby inhibiting hepatocellular carcinoma progression.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720009","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":"HILPDA Repression Induces Methuosis in Breast and Liver Cancer Cells by Dysregulating Lipid Metabolism","authors":"Jie Wang,&nbsp;Chuanxin Zhai,&nbsp;Chengfei Zhang,&nbsp;Anlian Fan,&nbsp;Sajid Jalal,&nbsp;Ting Zhang,&nbsp;Ting Xu,&nbsp;Chuanzhou Gao,&nbsp;Xinran Chen,&nbsp;Hongming Teng,&nbsp;Yuanyuan Luo,&nbsp;Cong Li,&nbsp;Lin Huang","doi":"10.1002/biof.70142","DOIUrl":"https://doi.org/10.1002/biof.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Perturbation of macropinocytosis triggers methuosis, a non-apoptotic cell death characterized by cytoplasmic vacuolization. However, the regulatory mechanisms of methuosis remain poorly defined. Lipid metabolism dysregulation is implicated in various cell death pathways, while its role in methuosis has remained elusive. Herein, LXX-8250, an isopropanolamine derivative of β-elemene, induced a vacuolization-associated cell death in breast and liver cancer cell lines. This process was accompanied by massive macropinocytosis, thereby confirming the occurrence of methuosis. Mechanistically, hypoxia-inducible lipid droplet-associated protein (HILPDA), a key regulator that promotes intracellular triacylglycerol (TAG) accumulation, was identified as the direct target of LXX-8250. By suppressing HILPDA, LXX-8250 inhibited diacylglycerol O-acyltransferase 1 (DGAT1) and activated adipose triglyceride lipase (ATGL). Consequently, lipid droplets and cellular TAG levels were reduced, while the subsequent increased diacylglycerol (DAG) stimulated macropinosome formation, leading to methuosis in these cells. In this study, we discover a novel methuosis agonist LXX-8250, and elucidate the critical role of HILPDA repression-dysregulated lipid metabolism in methuosis. Our study highlighted the potential of targeting this pathway as a therapeutic strategy to trigger cancer cell death.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753738","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":"Differential Modulation of Keratinocyte Proliferation, Differentiation, and Barrier Function by Hemp Oil, Blackcurrant Seed Oil, and Vitamin D3 Under Atopic-Associated Cytokine Stimulation","authors":"Daniel Tortolani,&nbsp;Lucia Scipioni,&nbsp;Alessandro Anselmucci,&nbsp;Francesca Ciaramellano,&nbsp;Meri Di Leonardo,&nbsp;Isa Fusaro,&nbsp;Sergio Oddi,&nbsp;Alessandro Gramenzi","doi":"10.1002/biof.70137","DOIUrl":"10.1002/biof.70137","url":null,"abstract":"<p>Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation, altered differentiation, barrier dysfunction, and oxidative stress. Currently available therapies, including monoclonal antibodies and JAK inhibitors, have improved AD management but do not address all aspects of the disease, supporting the investigation of natural-product strategies as complementary approaches to long-term care. An acute in vitro model of canine atopic-like inflammation was established by exposing canine progenitor epidermal keratinocytes (CPEK) for 24 h to a defined cytokine cocktail (IFN-γ, IL-4, IL-13), followed by 24 h of treatment with hemp oil, blackcurrant seed oil, vitamin D₃, or their combination. Proliferation (Ki-67, cell-cycle), differentiation (KRT5, KRT10, TGM1, involucrin), tight-junction organization (CLDN1, TJP1, ZO-1, TEER), wound closure, nitrosative stress (3-nitrotyrosine), the NRF2/BACH1/HMOX1 axis, and the secretion of STAT1- and NF-κB-dependent inflammatory mediators (CXCL9, CXCL10, IL-8, IL-6) and the STAT6-targeted chemokine CCL17 were assessed. The cytokine cocktail induced a coherent AD-like phenotype: increased Ki-67, downregulated CLDN1, sustained nitrosative stress, NRF2 elevation paralleled by BACH1 induction, and robust secretion of STAT1- and NF-κB-dependent mediators. The four treatments modulated this phenotype according to clearly differential, pathway-specific profiles. Vitamin D₃, alone or combined, emerged as the most effective modulator of proliferation and acted preferentially on the downstream redox arm, inducing HMOX1 and reducing BACH1; both vitamin D₃-containing formulations exerted broad anti-inflammatory activity across the STAT1 and NF-κB axes. Hemp oil acted preferentially on tight-junction integrity (CLDN1 recovery), on the upstream NRF2 arm (NFE2L2 induction), on the STAT1 chemokine arm (CXCL9, CXCL10 reduction), and on wound closure. Blackcurrant seed oil acted preferentially on NF-κB-dependent IL-8 and on early wound-closure dynamics. This differential pharmacological footprint provides a rational basis for further investigation of these formulations as nutraceutical adjuncts in canine AD.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705225","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":"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}