Cytotechnology最新文献

{"title":"USP8 stabilizes GPR37 via deubiquitination to regulate colorectal cancer progression through the NRF2/SLC7A11/GPX4 pathway.","authors":"Rong-Hua Zhu, Gang Dai, Ren-Tao Yu, Jie Zhang","doi":"10.1007/s10616-026-01063-y","DOIUrl":"10.1007/s10616-026-01063-y","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a prevalent malignancy with poor prognosis. Ferroptosis, an iron-dependent and non-apoptotic form of cell death characterized by lipid reactive oxygen species accumulation, has emerged as a critical process in CRC progression. The present study focuses on the regulatory mechanism through which ubiquitin-specific protease 8 (USP8) and G protein-coupled receptor 37 (GPR37) modulate ferroptosis in CRC. RT-qPCR and Western blotting were utilized to assess mRNA and protein expression, respectively. Cell viability, proliferation, apoptosis, migration, invasion, and angiogenesis were assessed using MTT, EdU, TUNEL, wound healing, transwell, and tube formation assays. The interaction and stability between USP8 and GPR37 were evaluated through co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase, and ubiquitination assays. Ferroptosis-related indicators were detected using corresponding commercial kits. A mouse xenograft model was established to confirm in vivo effects. GPR37 was highly expressed in CRC tissues and cells. Silencing GPR37 inhibited cell viability, migration, and invasion, and promoted ferroptosis. USP8 stabilized GPR37 protein expression via deubiquitination, and overexpression of GPR37 reversed the tumor-suppressive effects caused by USP8 knockdown. Modulation of the USP8/GPR37 axis was accompanied by corresponding changes in NRF2, SLC7A11, and GPX4 protein expression. In vivo, GPR37 overexpression rescued the inhibitory effect of USP8 knockdown on tumor growth. USP8-mediated stabilization of GPR37 may contribute to ferroptosis resistance and CRC progression, potentially involving NRF2/SLC7A11/GPX4 signaling.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01063-y.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"197"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angelica sinensis polysaccharide reduces macrophage FPR2 to regulate the hepatic inflammatory microenvironment and activate the PI3K/AKT signaling pathway to improve insulin resistance.","authors":"Zhisheng Duan, Jiarui Peng, Hong Zhu, Bin Ruan, Mei Cao","doi":"10.1007/s10616-026-01071-y","DOIUrl":"10.1007/s10616-026-01071-y","url":null,"abstract":"<p><p>Angelica sinensis polysaccharide (ASP) is one of the main active components of Angelica sinensis and has a significant ameliorative effect on high-fat diet (HFD)-induced insulin resistance (IR). This study aims to investigate the effect of ASP on IR and its mechanism. The in vivo IR model was established by HFD feeding in SD rats, and the in vitro IR model was constructed by insulin treatment in HepG2 cells. Fasting insulin levels were detected using assay kits; intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were used to evaluate the metabolic responses to glucose and insulin loads, respectively. HE staining was performed to observe pathological changes in liver tissues. RT-qPCR, Western blot, immunofluorescence, immunohistochemistry, and ELISA were employed to detect key genes and proteins expression. HFD rats showed significantly increased body weight, fasting blood glucose, insulin levels, and FPR2 expression. FPR2 knockdown alleviated pathological damage in liver tissues, reduced the expression of glucose metabolism-related genes G6pase, PEPCK, and GSK3β, and mitigated IR in HFD rats, and inhibited LPS-induced M1 polarization of macrophages, promoted M2 polarization. Mechanistically, treatment with LPS-induced macrophage culture medium reduced glucose uptake capacity and PI3K/AKT pathway activity in HepG2-IR cells, increased extracellular glucose content, and upregulated glucose metabolism-related gene expression. However, treatment with culture medium from FPR2-knockdown and LPS-induced macrophages reversed these abnormalities. Further treatment with the PI3K inhibitor LY294002 blocked this protective effect. Additionally, ASP treatment reduces HFD-induced FPR2 expression, restored PI3K/AKT pathway activity, alleviated IR in HFD rats, and FPR2 overexpression weakened the protective effects of ASP. ASP improves IR in rats by downregulating FPR2 expression, inhibiting M1 macrophage-mediated hepatocyte inflammatory responses, and activating the PI3K/AKT signaling pathway.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01071-y.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"202"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX4 facilitates osteogenic differentiation through suppressing NLRP3 transcription-mediated pyroptosis.","authors":"Ping Li, Xue-Yi Lin, Yu Lin, Yan Liu, Wei-Bing Yang","doi":"10.1007/s10616-026-01040-5","DOIUrl":"10.1007/s10616-026-01040-5","url":null,"abstract":"<p><p>SOX4 participates in cell differentiation, but its regulatory function and underlying mechanism in the osteogenic differentiation of MC3T3-E1 cells remain elusive. Immunofluorescence staining was used to detect SOX4 subcellular localization and co-localization with NLRP3. Alizarin Red staining was applied to evaluate osteogenic differentiation. RT-PCR and Western blot assays quantified mRNA and protein levels of SOX4, osteogenic markers (OPN, OCN, RUNX2), inflammatory cytokines, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD). JASPAR predicted SOX4 binding sites in the NLRP3 promoter and ChIP-qPCR was used to validate it. Dual-luciferase reporter assay was applied to assesse transcriptional regulation. Rescue experiments were performed via co-transfection of SOX4 and NLRP3 overexpression vectors. SOX4 was upregulated during MC3T3-E1 osteogenic differentiation. SOX4 overexpression reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, and inhibited pyroptosis. SOX4 directly bound to the NLRP3 promoter to suppress its transcription. NLRP3 overexpression reversed SOX4-induced enhancement of osteogenic differentiation and marker expression. SOX4 promotes MC3T3-E1 osteogenic differentiation by directly inhibiting NLRP3 transcription, thereby regulating inflammation and pyroptosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-026-01040-5.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"172"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the apoptotic properties of ergolide, a sesquiterpene lactone form <i>Inula oculus-christi</i>, in hepatocellular carcinoma.","authors":"Mahboubeh Irani, Behnaz Keramatian, Leila Ara, Maryam Hamzeloo-Moghadam","doi":"10.1007/s10616-026-01069-6","DOIUrl":"10.1007/s10616-026-01069-6","url":null,"abstract":"<p><p>Hepatocellular carcinoma is the most common and fatal liver cancer. Chronic liver disease, cirrhosis, and even nonalcoholic fatty liver disease can come up to hepatocellular carcinoma. Regarding the recent interests in natural products as sources of drug discovery, and considering the confirmed role of sesquiterpene lactones against several cancer cells, the effects of ergolide, a sesquiterpene lactone from Asteraceae family, was evaluated against HepG2 hepatocellular carcinoma to reveal the capabilities of this natural compound for confronting liver cancer. Ergolide was isolated from the chloroform extract of <i>Inula oculus-christi</i> aerial parts and its structure was confirmed with NMR data analysis. Proliferation of HepG2 cells treated with ergolide was assessed by MTT method and the IC₅₀ was calculated. Real time- PCR was used for evaluating gene transcription of apoptosis markers caspase 3, caspase 8, caspase 9, Bax and Bcl2. The expression of proteins of the above mentioned markers was assessed with Western blotting technique. The IC₅₀ of 48 h exposure of HepG2 cells to ergolide was found to be 7.2 µM. The pro-apoptotic genes and expression of protein markers of caspase 3, caspase 8, caspase 9, Bax were significantly upregulated at this concentration and even its half (IC_50/2) = 3.6). The anti-apoptotic gene and protein Bcl2 were downregulated at both of these concentrations. Ergolide may represent a promising lead compound in further preclinical investigation for liver cancer studies.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01069-6.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"199"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCDHGB2 promotes docetaxel resistance in prostate cancer via TR4-mediated activation of the HIF-1α/VEGFA pathway.","authors":"Fanyu Meng, Xinyi Zhou, Yong Qin, Pengju Liu","doi":"10.1007/s10616-026-01051-2","DOIUrl":"https://doi.org/10.1007/s10616-026-01051-2","url":null,"abstract":"<p><p>Prostate cancer poses a significant threat to men's health worldwide. Docetaxel (DTX) remains a cornerstone chemotherapeutic agent for PC, yet the emergence of docetaxel resistance has critically compromised clinical outcomes. Elucidating the molecular mechanisms underlying docetaxel resistance and identifying novel therapeutic targets are therefore imperative. This study integrated transcriptomic profiles and clinical data from the The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) and Gene Expression Omnibus (GEO) databases to identify <i>PCDHGB2</i> as a pivotal gene associated with docetaxel resistance. Bioinformatics analyses were systematically conducted to evaluate correlations between <i>PCDHGB2</i> expression, tumor microenvironment heterogeneity, clinicopathological characteristics, and patient prognosis. Experimental validation included quantitative real-time PCR (RT-qPCR) and immunofluorescence for expression profiling, Cell Counting Kit-8 (CCK-8) assays for cellular viability assessment, alongside co-immunoprecipitation and molecular docking to characterize protein interactions. Our findings demonstrate that PCDHGB2 serves as a central mediator of docetaxel resistance in PC, exhibiting significant associations with tumor microenvironment heterogeneity. Spatial analysis revealed differential <i>PCDHGB2</i> distribution across prostate carcinoma cell subtypes, correlating with tumor invasiveness. Mechanistically, PCDHGB2 directly binds to testicular receptor 4 (TR4), stabilizing its expression and subsequently activating the hypoxia-inducible factor 1-alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling axis to drive chemoresistance. To our knowledge, this study provides an initial comprehensive analysis of PCDHGB2's functional role in prostate cancer, uncovers a poorly recognized epigenetic mechanism of docetaxel resistance, and suggests a theoretical framework for improving prognostic strategies in prostate cancer patients.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-026-01051-2.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"181"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of tetrandrine on the i<i>n vitro</i> proliferation and differentiation of black sea bream (<i>Acanthopagrus schlegelii</i>) myogenic cell lines.","authors":"Chae Wan Kang, Eun Soo Jeong, Dan Hee Han, Jae Hoon Choi, Seung Pyo Gong","doi":"10.1007/s10616-026-01061-0","DOIUrl":"10.1007/s10616-026-01061-0","url":null,"abstract":"<p><p>Teleost myogenesis differs from mammalian systems, and well-characterized fish myogenic cell models remain limited. Tetrandrine, a bisbenzylisoquinoline alkaloid, impairs myogenesis and induces atrophy-associated responses in mammalian models, but its effects on teleost myogenic cells remain unclear. This study examined tetrandrine responses in black sea bream (<i>Acanthopagrus schlegelii</i>) myogenic cell lines. Cells were treated with tetrandrine to assess cytotoxicity, proliferative growth, myogenic differentiation, and associated cellular responses. Tetrandrine showed concentration-dependent cytotoxicity at higher concentrations, and 1, 3, and 5 µM were selected for subsequent experiments. Under growth conditions, tetrandrine exerted modest, cell line-dependent effects on proliferation. In contrast, tetrandrine markedly inhibited myogenic differentiation, as shown by reduced myotube formation, decreased fusion index, and suppressed expression of myogenic regulatory genes, including <i>Pax7</i>, <i>MyoD</i>, <i>Myog</i>, and <i>MyHC</i>. To examine whether proteolytic or oxidative stress-related processes contributed to this phenotype, cells were co-treated with MG-132, chloroquine, or N-acetylcysteine. These treatments did not restore tetrandrine-impaired myotube fusion, although MG-132 partially restored <i>MyHC</i> expression and tetrandrine induced a cell line-dependent increase in intracellular ROS. Fluo-4-based Ca²⁺ measurements further showed that acute tetrandrine treatment attenuated KCl-induced Ca²⁺ responses in differentiated cells, whereas undifferentiated cells showed little change. These findings suggest that altered depolarization-linked Ca²⁺ handling may contribute to tetrandrine-associated inhibition of myogenic differentiation in this teleost cell system.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01061-0.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"193"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-treatment with pyrvinium pamoate and hispidulin potently reduces stemness and promotes mitochondrial apoptosis in prostate cancer cells.","authors":"Riza Serttas, Suat Erdogan","doi":"10.1007/s10616-026-01056-x","DOIUrl":"10.1007/s10616-026-01056-x","url":null,"abstract":"<p><p>Pyrvinium pamoate, originally developed for protozoal infections, has emerged as a small-molecule inhibitor that interferes with Wnt/β-catenin signaling by suppressing β-catenin stability and downstream target gene activation. Wnt/β-catenin signaling pathway is a key intracellular regulatory mechanism of cellular proliferation and plays a particularly critical role in the maintenance of cancer stem cells. Accordingly, targeting cancer stem cells has become a major focus in the development of effective anticancer strategies, since these cells are primarily responsible for metastasis and disease relapse. Hispidulin is a natural flavonoid that has been shown to be effective on cell migration. In present study, PC3 castration-resistant human prostate cancer cells and RWPE-1 HPV-18-immortalized prostate epithelial cells were used. The antiproliferative, apoptotic and antimigrative effects of the combined use of pyrvinium pamoate and hispidulin on prostate cancer cells were analyzed by MTT test. The effects of hispidulin and pyrvinium pamoate on metastasis ability of PC3 cells were analyzed by wound healing assay. Proliferation- and cancer stem cell-related genes were analyzed by qPCR, and apoptotic bodies were visualized by Hoechst staining. Potential antimigratory effect of pyrvinium pamoate and hispidulin was showed not only in wound healing assay but also real time PCR. Besides, quantification analyses of mRNA synthesized from <i>SOX2</i>, <i>OCT3/4</i>, <i>NANOG</i> and <i>WNT10</i> genes exhibited that cancer stem cells were affected by hispidulin and pyrvinium pamoate. It was showed that the results were obtained will contribute to the development of stem cell-targeted methods in cancer treatment strategies.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"186"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADH1 dysfunction exacerbates neurovascular injury in diabetic stroke by impairing 4-HNE clearance and promoting neutrophil infiltration.","authors":"Pei-Pei Xu, Ying-Na Shi","doi":"10.1007/s10616-026-01058-9","DOIUrl":"10.1007/s10616-026-01058-9","url":null,"abstract":"<p><p>Diabetes significantly exacerbates ischemic stroke injury, yet the underlying metabolic-inflammatory mechanisms remain elusive. This study investigates the role of Alcohol Dehydrogenase 1 (ADH1) in the pathophysiology of neurovascular injury following diabetic stroke. Diabetic mice were established via intraperitoneal injection of streptozotocin. Distal middle cerebral artery occlusion (dMCAO) was performed to induce ischemic stroke. In vitro, primary microglia and endothelial cells were exposed to high glucose (HG) and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Transcriptomic analysis of a public dataset (GSE196266) identified key differentially expressed genes, including ADH1. In vivo, ADH1 function was assessed via intracerebroventricular injection of adeno-associated virus (AAV)-ADH1 vector. Infarct volume was quantified via 2,3,5-triphenyltetrazolium chloride (TTC) staining; neurological deficits were assessed using the modified Neurological Severity Score (mNSS); 4-HNE levels were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot; neutrophil infiltration was quantified via flow cytometry and microglial polarization were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). ADH1 was significantly downregulated in diabetic stroke brains. Overexpression of ADH1 markedly reduced infarct volume and cerebral edema while improving long-term neurological recovery. Mechanistically, ADH1 attenuated oxidative stress by facilitating the clearance of 4-hydroxy-2-nonenal (4-HNE), which subsequently inhibited microglial M1 polarization and apoptosis. Furthermore, ADH1 preserved BBB integrity by preventing 4-HNE-mediated impairment of tight junction protein integrity (ZO-1, OCLN, CLDN5) and suppressed neutrophil recruitment by downregulating chemotactic signals (CXCL1/2). Exogenous 4-HNE treatment directly exacerbated these pathological processes, whereas ADH1 restoration effectively rescued the neurovascular unit. ADH1 dysfunction exacerbates neurovascular injury in diabetic stroke by impairing 4-HNE clearance and promoting neutrophil infiltration. Targeting the ADH1/4-HNE axis represents a promising therapeutic strategy for ameliorating diabetic stroke outcomes.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"196"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL14 knockdown alleviates inflammation in oral lichen planus by driving macrophage M2 polarization through mediating FDX1 m6A modification.","authors":"Xuan-Jiang Shen, Jun Luo, Yu-Kang Ying, Hai-Qian Zhu","doi":"10.1007/s10616-026-00981-1","DOIUrl":"https://doi.org/10.1007/s10616-026-00981-1","url":null,"abstract":"<p><p><i>Background</i> Oral lichen planus (OLP) is a prevalent chronic disease affecting the oral mucosa, and its pathogenesis remains not fully understood. This study aims to examine the regulatory mechanism of METTL14/FDX1 in the development of OLP. <i>Methods</i> Macrophage polarization and METTL14/FDX1 expression were analyzed in mucosal tissues from OLP patients and controls via immunofluorescence, RT-qPCR, and ELISA. In vitro, THP-1-derived macrophages were transfected with METTL14 or FDX1 targeting/overexpression vectors to assess their roles in polarization (flow cytometry) and cytokine secretion (ELISA). The METTL14-FDX1 interaction and m6A modification were confirmed by RIP and MeRIP-PCR. Functional outcomes were evaluated in a macrophage-keratinocyte co-culture system (flow cytometry) and in an imiquimod-induced OLP mouse model treated with sh-METTL14. <i>Results</i> The abnormal accumulation of M1 macrophage was identified in mucosa of OLP patients. Upregulation of m6A-related key enzyme METTL14 was identified in macrophages of OLP patients, which was associated with inflammation of OLP. Mechanically, METTL14 knockdown reduced mRNA stability of FDX1 through m6A modification, thereby limiting the transcriptional expression of FDX1 in macrophage. Functionally, METTL14 overexpression promoted macrophage M1 polarization through upregulating FDX1. Additionally, macrophages with METTL14 knockdown inhibited keratinocytes apoptosis by polarizing to M2. In vivo, METTL14 knockdown alleviated inflammation in OLP mouse model by driving macrophage M2 polarization. METTL14, via upregulating FDX1, also promoted the production of T-helper cell-associated inflammatory cytokines (IFN-γ, IL-17) integral to OLP pathology. <i>Conclusion</i> METTL14 knockdown alleviates inflammation in OLP by driving macrophage M2 polarization through mediating FDX1 m6A modification.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"177"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming in pancreatic cancer: interplay of glucose, lipid, and amino acid metabolism in tumor progression.","authors":"Zeliang Zhang, Ying Tian, Bo Zhang, Kexiang Zhu","doi":"10.1007/s10616-026-01052-1","DOIUrl":"https://doi.org/10.1007/s10616-026-01052-1","url":null,"abstract":"<p><p>Pancreatic cancer is one of the most malignant solid tumors, with a five-year survival rate of less than 10%. The therapeutic challenges primarily stem from difficulties in early diagnosis, high heterogeneity, and extensive resistance to chemotherapy, targeted therapy, and immunotherapy. Recent studies have revealed that metabolic reprogramming, a core hallmark of cancer, is a key mechanism driving the malignant phenotype of pancreatic cancer, persisting throughout its initiation, progression, and development of treatment resistance. This article systematically reviews the molecular mechanisms underlying the dysregulation of three major nutrient metabolic pathways-glucose, lipid, and amino acid metabolism-and their interconnected regulatory networks. Regarding glucose metabolism, enhanced aerobic glycolysis and PPP activation collectively support tumor growth, redox maintenance, and microenvironmental remodeling, whereas lactate accumulation further contributes to immune evasion. Lipid metabolic reprogramming is characterized by coordinated alterations in de novo synthesis, fatty acid oxidation, and cholesterol homeostasis, which collectively regulate membrane remodeling, stemness maintenance, and therapeutic resistance. Amino acid metabolism is characterized by glutamine dependency and branched-chain amino acid metabolic reprogramming, which collectively support biosynthesis, redox homeostasis, and tumor adaptation. These three major metabolic pathways do not operate in isolation but form a dynamic, interconnected network. This network confers robust metabolic plasticity and adaptability to the tumor, constituting a fundamental basis for treatment resistance. Concurrently, stromal cells and immune cells within the tumor microenvironment also undergo metabolic reprogramming, forming a metabolic symbiotic system with cancer cells that further exacerbates treatment resistance. Although combination strategies targeting metabolic pathways-such as glycolysis inhibitors combined with gemcitabine, statins synergizing with chemotherapy, or metabolic interventions combined with immunotherapy-have shown promise in preclinical models, clinical translation remains challenging. These challenges arise from multiple factors, including tumor heterogeneity, metabolic compensation, drug delivery limitations, and the complexity of the tumor microenvironment. Future efforts should integrate single-cell metabolomics, organoid models, and multimodal imaging technologies to advance precision therapy based on metabolic subtyping. Additionally, the development of novel nanodelivery systems and multi-target combination regimens is needed to bridge the gap from mechanistic understanding to clinical application. Metabolic intervention holds potential not only for advanced-stage treatment but also for chemoprevention at the precancerous lesion stage, offering a novel approach to improving the prognosis of pancreatic cancer.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"78 5","pages":"179"},"PeriodicalIF":2.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}