Tissue & cell最新文献

{"title":"Combined inhibition of WEE1 by AZD1775 synergistically enhances CX-5461 mediated DNA damage and induces cytotoxicity in glioblastoma","authors":"Meng Cheng ,&nbsp;Rui Wang ,&nbsp;Ying Pang ,&nbsp;Xu Chen ,&nbsp;Jing Zhang ,&nbsp;Chunlong Zhong","doi":"10.1016/j.tice.2025.103093","DOIUrl":"10.1016/j.tice.2025.103093","url":null,"abstract":"<div><div>Glioblastoma (GBM) is an extremely aggressive type of central nervous system tumors that poses treatment challenges due to its resistance to DNA-damaging therapies. G-quadruplexes (G4) are non-canonical DNA structures involved in genomic stability and transcription regulation, and they have emerged as potential therapeutic targets. Originally developed as an RNA polymerase I inhibitor, CX-5461 has been demonstrated to enhance G4 stabilization and induce DNA damage; however, its effects on GBM remain underexplored. This study investigated the effects of CX-5461 on GBM cell biological functions. CX-5461 treatment significantly inhibited DNA replication and induced apoptosis in GBM. S-phase arrest in cell cycle analysis indicated replication stress, and DNA damage assays revealed extensive double-strand<!--> <!-->breaks. CX-5461 disrupted the DNA damage response by stabilizing G4 structures, resulting in sustained DNA damage accumulation. Moreover, the combined administration of CX-5461 and the WEE1 inhibitor AZD1775 synergistically decreased cell proliferation and enhanced cell apoptosis. Consequently, these results suggest that CX-5461 inhibited GBM progression by stabilizing G4, causing replication stress and exacerbating DNA damage. Targeting G4 structures, especially when combined with checkpoint inhibitors, provides a hopeful therapeutic approach to improve the effectiveness of GBM therapy.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103093"},"PeriodicalIF":2.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ageing on the structural compositions of the mucosa of human colon","authors":"Nicholas Baidoo ,&nbsp;Enrica De Rasis ,&nbsp;Dion Tahiri ,&nbsp;Gareth J. Sanger","doi":"10.1016/j.tice.2025.103090","DOIUrl":"10.1016/j.tice.2025.103090","url":null,"abstract":"<div><div>The increased prevalence of chronic constipation, faecal impaction and incontinence among older individuals have been linked in part, to age-related degenerative changes within the bowel. In aged laboratory animals, increased mucosal permeability has been associated with overall loss of mucosal integrity, but equivalent studies have not been conducted for the human colon. We address this knowledge gap by examining the number of intestinal stem cells and epithelial tight junction proteins, and densities of connective tissues, namely total collagen and elastin, on macroscopically normal ascending (AC; adults: 30–52 years and elderly: 70 – 89 years) and descending (DC; adults: 42–60 years and elderly: 67 – 82 years) colon using immunohistochemistry and tinctorial staining techniques. The results demonstrated that in the ageing AC but not clearly in the DC, there was a significant decline in anti-junctional adhesion molecule-A, anti- occludin and anti-zonula occluden-1 tight junction protein expressions within the epithelium per mucosal unit area. Compared to younger adults, there was no consistent change in anti-claudin-2 protein in the DC from older adults (p = 0.068), but the level of expression tended to increase in the AC (p = 0.059). The number of olfactomedin-4 positive cells tended to be smaller (mean value: AC; 5.2 ± 0.6 vs. 4.9 ± 0.2/ crypt and DC: 5.6 ± 0.8 vs. 5.1 ± 0.3) but were not statistically significant with increasing age in both regions. Ageing increased the amount of elastin fibres within the <em>muscularis mucosae</em> in AC and DC, and there was a tendency for total collagen fibres to increase in the mucosa of the older adults DC (p = 0.061). These structural changes in the aged mucosa have potential to impact colonic functions and may contribute to the development of lower bowel disorders in a region-specific manner.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103090"},"PeriodicalIF":2.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ONECUT1 activates PSAT1 to facilitate PD-L1 expression and mediate immune evasion of lung squamous cell carcinoma","authors":"Xiaoyan Huang ,&nbsp;Jingwei Yan ,&nbsp;Shucong Peng,&nbsp;Yifan Zhou,&nbsp;Shangwei Chen","doi":"10.1016/j.tice.2025.103091","DOIUrl":"10.1016/j.tice.2025.103091","url":null,"abstract":"<div><h3>Background</h3><div>PD-1/PD-L1, a classic immune checkpoint commonly employed in targeted therapy, has proven to yield only limited benefits for patients with lung squamous cell carcinoma (LUSC). Unraveling the intrinsic mechanisms underlying the progression of LUSC serves as the foundation for discovering more effective treatment strategies.</div></div><div><h3>Methods</h3><div>A study was conducted on the differential expression of PSAT1 and ONECUT1 in LUSC based on data from the TCGA database. Pearson correlation analysis was undertaken to examine the association between PSAT1 expression and CD8⁺ T-cell infiltration or ONECUT1 expression in LUSC. Based on the hTFtarget and JASPAR databases, upstream regulators and potential binding sites for PSAT1 were screened and predicted. An analysis of the prognostic impact of PSAT1 on lung cancer was based on the Kaplan-Meier Plotter website. In qPCR analysis, the mRNA expression of PSAT1 and ONECUT1 was detected. Clinical samples of tumor tissue and adjacent normal tissues were collected, with IHC analysis undertaken on them to determine the PSAT1 protein content, as well as the infiltration level of CD8⁺ T cells in the tumor tissue. Through MTT, cell viability was evaluated. Western blot (WB) was utilized to detect the expression of PD-L1 protein. The ANNEXIN V-FITC experiment was carried out to assess the level of apoptosis in cancer cells. CFSE, ELISA, and Transwell experiments were all employed to assess the activation level and chemotaxis of CD8⁺ T cells. ChIP and dual luciferase assay were carried out to investigate the binding relationship between ONECUT1 and PSAT1.</div></div><div><h3>Results</h3><div>In tumors and LUSC lines, PSAT1 exhibited significant overexpression, which was linked with adverse prognosis and inversely correlated with CD8⁺ T cell infiltration. In PSAT1-overexpressing tumor tissues, the infiltration level of CD8⁺ T cells was greatly lower than that in tissues with low PSAT1 expression. Knocking down PSAT1 considerably decreased the viability and expression of PD-L1 protein in LUSC cells, as well as upregulated apoptosis levels and the activation and chemotactic capacity of CD8⁺ T cells in co-culture systems. ONECUT1 was a potential upstream regulator of PSAT1, displaying a positive correlation and possessing potential binding sites within the promoter region of PSAT1. Furthermore, ONECUT1 had remarkable overexpression in LUSC tissues and cells. The ChIP and dual luciferase assays confirmed that ONECUT1 effectively bound to PSAT1 and activated PSAT1 expression. Overexpression of ONECUT1 restored the negative regulation on cell viability and positive activation effect on CD8⁺ T cells caused by PSAT1 knockdown.</div></div><div><h3>Conclusion</h3><div>ONECUT1 transcriptionally activates PSAT1 to reinforce LUSC immune evasion through upregulation of PD-L1 expression.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103091"},"PeriodicalIF":2.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of NF-κB/NLRP3 inflammasome axis and oxidative stress, and upregulation of Nrf2/HO-1 signaling mediate the protective effect of S-carboxymethylcysteine against cyclophosphamide-induced cardiotoxicity","authors":"Reem S. Alruhaimi ,&nbsp;Emad H.M. Hassanein ,&nbsp;Sulaiman M. Alnasser ,&nbsp;Ahmad F. Ahmeda ,&nbsp;Hanan S. Althagafy ,&nbsp;Amr M.T. Allam ,&nbsp;Hamada S. Qebesy ,&nbsp;Ayman M. Mahmoud","doi":"10.1016/j.tice.2025.103092","DOIUrl":"10.1016/j.tice.2025.103092","url":null,"abstract":"<div><div>Cyclophosphamide (CP) is a potent chemotherapeutic and immunosuppressant agent used in the management of lymphoproliferative disorders and solid tumors. However, it induces cardiotoxicity and other severe adverse effects, thereby limiting its clinical application, highlighting the need for safe and effective cardioprotective agents. This study investigates the cardioprotective potential of carbocysteine (S-carboxymethylcysteine (SCMC)), a mucolytic agent with emerging pleiotropic properties, against CP-induced toxicity. The study explores the effect of SCMC on oxidative stress, NF-κB/NLRP3 inflammasome axis and Nrf2/HO-1 signaling. Rats received SCMC for 7 days and a single CP dose on day 5. CP provoked severe cardiac injury, evidenced by increased CK-MB, LDH, and troponin-I, alongside histopathological alterations, including vascular congestion, cytoplasmic vacuolation, hypertrophy, and nuclear pyknosis. SCMC significantly alleviated cardiac biomarkers and mitigated tissue damage in CP-treated rats. CP increased MDA, decreased antioxidants, increased cardiac NF-κB, IL-1β, and gasdermin D, upregulated NLRP3, ASC1, and caspase-1, and diminished Nrf2 and HO-1. SCMC reduced MDA, enhanced antioxidant defenses, and downregulated NF-κB, NLRP3, ASC, caspase-1, gasdermin D, and IL-1β in CP-administered rats. In addition, SCMC enhanced the expression of Nrf2 and activity of HO-1 in the heart of CP-administered rats. In conclusion, these findings demonstrate that SCMC mitigates CP-induced cardiotoxicity by targeting oxidative injury and inflammatory signaling. Its cardioprotective mechanism includes mitigation of oxidative stress and NF-κB/NLRP3 inflammasome axis, and upregulation of Nrf2/HO-1 pathway. Given its established clinical safety, SCMC may represent a translatable adjunctive therapy to protect against CP-induced cardiotoxicity. However, further studies and clinical trials are warranted to confirm these findings.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103092"},"PeriodicalIF":2.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypericin attenuates myocardial ischemia-reperfusion injury by enhancing mitochondrial energy metabolism via AMPK/PGC-1α signaling pathway","authors":"LI Huihui ,&nbsp;BAO Yali ,&nbsp;LI Wanyue ,&nbsp;XIN Huitian ,&nbsp;GAO Xiaofeng ,&nbsp;Dina AINIWAR ,&nbsp;LING Can ,&nbsp;Gulinigaer ANWAIER ,&nbsp;SUN Zhan","doi":"10.1016/j.tice.2025.103088","DOIUrl":"10.1016/j.tice.2025.103088","url":null,"abstract":"<div><h3>Background</h3><div>Although blood flow is restored following the treatment of acute myocardial infarction (AMI), myocardial Ischaemia /reperfusion can still cause cardiac damage, potentially leading to cardiac decompensation and, ultimately, heart failure. This study aimed to investigate the effects of Hypericin (Hyp) on the hearts of rats with myocardial ischaemia-reperfusion injury (MIRI) and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats and H9C2 cells underwent MIRI and hypoxia/reoxygenation (H/R) modelling after Hyp administration to assess the compound's effects on cardiac and cardiomyocyte characteristics, as well as mitochondrial energy metabolism. A range of techniques, including 2,3,5-triphenyltetrazolium chloride staining, haematoxylin-eosin staining, echocardiography, enzyme-linked immunosorbent assay, quantitative proteomics analysis, molecular docking, and Western blotting were employed to further characterize Hyp's cardioprotective effects and its influence on related molecular expressions. TUNEL staining and Western blotting were also used to examine the morphological, molecular, and functional phenotypes of H/R-treated cardiomyocytes.</div></div><div><h3>Results</h3><div>Hyp significantly reduced myocardial infarct size and improved cardiac function in MIRI rats. Hyp increased cardiomyocyte viability while decreasing cardiomyocyte damage. The cardioprotective effects of Hyp were primarily mediated by alleviating mitochondrial dysfunction and oxidative stress, mainly through the adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α) signalling pathway.</div></div><div><h3>Conclusion</h3><div>Hyp regulates the AMPK/PGC-1α signalling pathway to improve mitochondrial energy metabolism and reduce oxidative stress, thereby mitigating MIRI in rats.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103088"},"PeriodicalIF":2.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysophanol inhibits ischemia/reperfusion-induced neuronal pyroptosis by regulating NRF2/ARE/GSDMD signaling pathway","authors":"Feijian Zeng ,&nbsp;Yao Liang ,&nbsp;Yufei Wei ,&nbsp;Yonghua Huang ,&nbsp;Yan Yan ,&nbsp;Yongjun Wu ,&nbsp;Guihua Huang","doi":"10.1016/j.tice.2025.103082","DOIUrl":"10.1016/j.tice.2025.103082","url":null,"abstract":"<div><h3>Background</h3><div>Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke (IS). This study aimed to investigate the effects of CHR on cerebral ischemia/reperfusion (I/R).</div></div><div><h3>Methods</h3><div>MCAO/R was used to establish mouse IS model. Histological analysis was performed using Nissl staining. Neuronal loss was detected using TUNEL staining. OGD/R was used to establish <em>in vitro</em> cerebral I/R injury model. Gene expression was detected using RT-qPCR and Western blot. Cytokine release was detected using ELISA. Cellular functions were detected using CCK-8 assay, LDH assay, flow cytometry, and TUNEL staining. GSDMD transcription was detected using luciferase and ChIP assays.</div></div><div><h3>Results</h3><div>CHR alleviated OGD/R induced neuronal damage, as well as inhibited oxidative stress, inflammatory response, and neuronal pyroptosis <em>in vivo</em> and <em>in vitro</em>. CHR promoted the activation of NRF2/ARE signaling. NRF2 inhibited the transcription of GSDMD, resulting in its downregulation. However, inhibition of NRF2 signaling contributed to neuronal damage and pyroptosis.</div></div><div><h3>Conclusions</h3><div>CHR protects against cerebral I/R injury-induced neuronal loss by regulating NRF2/ARE/GSDMD signaling pathway. Therefore, CHR may be a promising strategy for cerebral I/R injury.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103082"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of alpha-pinene on the NLRP3-Caspase 1 pathway in the ulcerative colitis model in rats","authors":"Kaveh Rahimi ,&nbsp;Annahita Rezaie ,&nbsp;Arian Javadi ,&nbsp;Mahsa Khademi Kalantari ,&nbsp;Negar Eftekhar ,&nbsp;Hoora Shushtari","doi":"10.1016/j.tice.2025.103085","DOIUrl":"10.1016/j.tice.2025.103085","url":null,"abstract":"<div><div>Alpha-pinene is a natural compound that has recently attracted the attention of researchers due to its anti-inflammatory and antioxidant effects. This study aimed to investigate the impact of alpha-pinene on the NLRP3-Caspase 1 pathway activity in colon tissue in a colitis model. The colitis was induced by directly administering 4 % acetic acid (A.A) into the colon. Twenty-four hours after this treatment, the test compound alpha-pinene (at doses of 50 and 100 mg/kg), sulfasalazine (50 mg/kg), or the vehicle (liquid paraffin) was given orally. Seven days after inducing colitis, the colonic segments were examined for disease score index, changes in the colon weight/length ratio, oxidative stress factors, and NLRP3-Caspase 1 pathway activity. Alpha-pinene improved the disease score index and the colon weight/length ratio. Alpha-pinene balanced oxidative stress factors in acetic acid-induced colitis by reducing MDA levels and increasing GSH, SOD, and CAT levels. Additionally, alpha-pinene decreased NLRP3 pathway activity by reducing MAPK P38 activity, leading to decreased expression of NF-KB, NLRP3, and Caspase 1, as well as decreased levels of IL-1B and IL-18. Our research suggests that alpha-pinene may be effective in treating colitis by reducing oxidative stress and decreasing the activity of the NLRP3 caspase-1 pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103085"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting YBX1: A novel therapeutic strategy for gastric cancer through regulation of cellular senescence and mTOR signaling","authors":"Wenze Zhang ,&nbsp;Yanjuan Jia ,&nbsp;Anqi Wang ,&nbsp;Rui Guo ,&nbsp;Zhuomin Fu ,&nbsp;Wanxia Wang","doi":"10.1016/j.tice.2025.103089","DOIUrl":"10.1016/j.tice.2025.103089","url":null,"abstract":"<div><div>Gastric cancer (GC) continues to pose a significant challenge for treatment due to its heterogeneity and the limitations of current strategies. There is an urgent need to find new molecular targets and strategies that can overcome therapy limitations and enhance outcomes. The modern “one-two punch\" therapy involves inducing senescence and using a second drug to target senescent cancer cells, potentially offering an effective treatment. However, it remains an emerging research area for GC. In this study, we aimed to investigate the role of YBX1, a multifunctional RNA- and DNA-binding protein, in GC progression and its therapeutic potential in senescence-based strategies. We found that YBX1, which is elevated in gastric cancer cells and correlated with poor prognosis in gastric cancer patients, acts as a central hub linking the mTOR, ROS, and DDR pathways. YBX1 mRNA and protein levels were significantly higher in GC tissues than in adjacent normal tissues (P &lt; 0.001), and high expression was associated with reduced overall survival (P &lt; 0.05). Importantly, YBX1 promotes the proliferation of GC cells (P &lt; 0.01) and inhibits senescence by regulating the mTOR signaling pathway. Targeting YBX1 could offer a “one-two punch” therapeutic approach for GC, since inhibiting mTOR induces senolytic effects on senescent cancer cells. Furthermore, YBX1 knockdown increases ROS levels (P &lt; 0.0001) and disrupts DNA damage repair, enhancing its potential as a therapeutic target. In vivo xenograft studies confirmed that YBX1 inhibition reduces tumor growth and downregulates Ki67, pmTOR, and p4EBP1 expression (P &lt; 0.001), while upregulating cellular senescence markers (P &lt; 0.01), supporting its critical role in GC progression. Thus, this study underscores YBX1 as a pivotal regulator of GC cell proliferation, senescence, and survival, offering a promising avenue for targeted therapies. By leveraging YBX1 inhibition, this work lays a foundation for developing precision medicine approaches in GC treatment.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103089"},"PeriodicalIF":2.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scopoletin inhibits ovarian cancer progression by reducing glycolysis via the EGFR-AKT pathway","authors":"Xi Lin ,&nbsp;Yingying He ,&nbsp;Jingke Song ,&nbsp;Xiaomin Xu ,&nbsp;Jingui Xu ,&nbsp;Kening Zhou ,&nbsp;Lihua Zheng","doi":"10.1016/j.tice.2025.103086","DOIUrl":"10.1016/j.tice.2025.103086","url":null,"abstract":"<div><div>This study aimed to investigate the antitumor effects and mechanisms of scopoletin in chemoresistant ovarian cancer (OC) cells. Cell viability, migration, invasion, and the cell cycle were assessed. The effect of scopoletin on aerobic glycolysis was determined by measuring glucose uptake, lactate, ATP, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR). Bioinformatics was used to analyze the relationship between scopoletin and epidermal growth factor receptor (EGFR). The levels of p-EGFR and p-AKT were measured using western blotting. <em>In vivo</em> xenograft models were used to validate the role of scopoletin. These results revealed that scopoletin inhibited the viability, migration, invasion, and colony formation of chemoresistant OC cells. It induced concentration-dependent G1/S phase arrest and reversed aerobic glycolysis by reducing glucose uptake, lactate production, ATP levels, and ECAR while increasing the OCR. Scopoletin targets the EGFR-AKT axis and downregulates p-EGFR and p-AKT expression. Crucially, the combination of scopoletin and the EGFR inhibitor lapatinib synergistically inhibited cellular metabolic reprogramming and proliferation and significantly enhanced tumor growth inhibition in mice compared to single-drug treatment. In conclusion, scopoletin suppresses chemoresistant OC progression and metastasis by targeting the EGFR-AKT pathway. The synergistic effect of scopoletin and lapatinib demonstrates a promising therapeutic strategy for overcoming OC chemoresistance.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103086"},"PeriodicalIF":2.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin targets ANXA2 to suppress hepatocellular carcinoma angiogenesis through the PI3K/AKT signaling pathway","authors":"Lulu Cao ,&nbsp;Lihui Wang ,&nbsp;Jun Lin ,&nbsp;Jian Zhao ,&nbsp;Bolun Xu ,&nbsp;Jianxin Chen ,&nbsp;Juanjuan Hu ,&nbsp;Siwei Wang ,&nbsp;Junhua Yu","doi":"10.1016/j.tice.2025.103087","DOIUrl":"10.1016/j.tice.2025.103087","url":null,"abstract":"<div><h3>Background</h3><div>Annexin A2 (ANXA2), implicated in the progression of multiple cancers, is considered a promising biomarker for anti-cancer therapies. Our research explores the molecular mechanisms of ANXA2 in hepatocellular carcinoma (HCC) and discovers the potential of traditional Chinese medicine compounds to target ANXA2, aiming to improve current HCC therapeutic approaches.</div></div><div><h3>Methods</h3><div>Our study leveraged TCGA data to investigate ANXA2 expression in HCC, complemented by gene set enrichment analysis to elucidate its potential impact. We quantified ANXA2 expressions in HCC cells using qRT-PCR and western blot. Modulating ANXA2 expression, we used cell counting kit-8 to gauge cell viability and Transwell assays to measure invasiveness. Scratch and tube formation assays were conducted on human umbilical vein endothelial cells (HUVECs), and vascular endothelial growth factor A (VEGFA) levels were detected via enzyme-linked immunosorbent assay. Molecular docking with AutoDock and cell thermal shift assays established the binding affinity and targeting of dihydroartemisinin (DHA) to ANXA2.</div></div><div><h3>Results</h3><div>ANXA2 was upregulated in HCC tissues and cells and was particularly enriched in the PI3K/AKT signaling pathway. Knockdown of ANXA2 in HCC cells resulted in the inhibition of cell invasion and angiogenesis, while overexpression led to the opposite effects. We discovered a binding relationship between DHA and ANXA2, suggesting that the therapeutic effects of DHA on HCC are mediated through targeting ANXA2.</div></div><div><h3>Conclusion</h3><div>DHA, by engaging ANXA2, mitigates the PI3K/AKT signaling, thereby inhibiting invasive and angiogenic activities of HCC.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103087"},"PeriodicalIF":2.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}