Tissue & cell最新文献

{"title":"Neuroprotective effects of Tanshinone IIA in an acrylamide-induced in-vivo zebrafish model: Behavioral, biochemical and molecular restoration","authors":"Gokul Sudhakaran ,&nbsp;S. Madesh ,&nbsp;V.N. Dhaareshwar ,&nbsp;Mikhlid H. Almutairi ,&nbsp;Bader O. Almutairi ,&nbsp;Sungkwon Park ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.tice.2025.103114","DOIUrl":"10.1016/j.tice.2025.103114","url":null,"abstract":"<div><div>Acrylamide is a neurotoxic chemical widely present in carbohydrate-rich foods due to thermal processing. Chronic exposure to acrylamide can lead to oxidative stress, neuroinflammation, and neurodegeneration, resulting in motor dysfunction and cognitive impairments. In this study, we evaluated the neuroprotective potential of Tanshinone IIA (TIIA), a bioactive compound derived from <em>Salvia miltiorrhiza</em> (Danshen), on an adult zebrafish model induced with acrylamide. Zebrafish were exposed to acrylamide to induce neurotoxic stress, followed by treatment with varying concentrations of TIIA. Our results highlight that TIIA significantly improved survival rates and restored behavioral deficits caused by acrylamide, including impaired exploratory behavior and increased anxiety-like responses. Biochemically, TIIA restored antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT), which were reduced by acrylamide exposure, thereby mitigating oxidative stress. TIIA also decreased lactate dehydrogenase (LDH) activity, indicative of reduced cellular damage, and restored acetylcholinesterase (AChE) activity, crucial for cholinergic neurotransmission. At the molecular level, TIIA reduced the activity of pro-inflammatory genes by stopping transcription, which acrylamide had increased, and brought the levels of neuroprotective genes like <em>bdnf</em> and <em>nrf</em> back to normal. Additionally, histological investigation showed that TIIA treatment significantly restored the morphological damage caused by acrylamide in the brain tissue of zebrafish. We draw conclusions on TIIA's neuroprotective effectiveness against acrylamide-induced neurotoxicity, demonstrating its potential as a treatment to stop acrylamide processed foods from causing neurodegenerative diseases.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103114"},"PeriodicalIF":2.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926783","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":"Poly glycerol sebacate/poly lactide acid (PGS/PLA) hydrogel in combination with hyperbaric oxygen therapy improved full thickness wound healing in diabetic rat","authors":"Waheeb S. Aggad ,&nbsp;Amany I. Almars ,&nbsp;Fayez Alsulaimani ,&nbsp;Ahmed M. Basri ,&nbsp;Sameerah Shaheen ,&nbsp;Nahlah M. Ghouth ,&nbsp;Nada M. Ghouth ,&nbsp;Zaki H. Hakami ,&nbsp;Wajnat A. Tounsi ,&nbsp;Sawsan Abd Ellatif ,&nbsp;Mona H. Soliman ,&nbsp;Hailah M. Almohaimeed","doi":"10.1016/j.tice.2025.103113","DOIUrl":"10.1016/j.tice.2025.103113","url":null,"abstract":"<div><div>Chronic wounds, particularly in diabetic patients, pose significant therapeutic challenges due to impaired healing under ischemic conditions. This study investigated the synergistic effect of a poly glycerol sebacate/poly lactide acid (PGS/PLA) hydrogel combined with hyperbaric oxygen therapy (HBOT) on wound healing in a diabetic rat model. Full-thickness skin wounds were induced on the dorsum of rats and treated with PGS/PLA, HBOT, or their combination. Histological evaluations were performed using stereological techniques to quantify fibroblasts, neutrophils, and blood vessels. Collagen content was assessed by Masson's trichrome staining. Wound tensile strength, oxidative stress biomarkers (GSH, SOD, CAT, MDA), and expression levels of related genes (TGF-β, VEGF, bFGF, HIF-1α, TNF-α, IL-1β) were also analyzed. The results showed that the PGS/PLA+HBOT group significantly improved wound closure, increased fibroblast density, and reduced neutrophil count compared to other groups (p &lt; 0.05). Vascular density and collagen deposition were highest in the combined treatment group (p &lt; 0.05). Biomechanical analysis revealed enhanced tensile strength in all treated groups, with the combination group outperforming the others (p &lt; 0.05). Antioxidant levels were significantly elevated, while MDA levels were decreased, particularly in the PGS/PLA+HBOT group (p &lt; 0.05). Gene expression analysis showed increased levels of TGF-β, VEGF, and bFGF, and reduced expression of HIF-1α, TNF-α, and IL-1β in treated wounds (p &lt; 0.05). The combination of PGS/PLA nanofiber dressing with HBOT effectively accelerates wound healing by enhancing cellular proliferation, angiogenesis, collagen formation, redox balance, and modulation of inflammatory and regenerative gene expression. This strategy may offer a promising therapeutic approach for managing ischemic wounds.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103113"},"PeriodicalIF":2.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922730","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":"Lysophosphatidic acid-induced YAP activation regulates osteogenesis of MC3T3-E1","authors":"Qin Zhang ,&nbsp;Jiayi Liu ,&nbsp;Bingfeng Wu ,&nbsp;Ying Yuan ,&nbsp;Ping Gong ,&nbsp;Lin Xiang","doi":"10.1016/j.tice.2025.103111","DOIUrl":"10.1016/j.tice.2025.103111","url":null,"abstract":"<div><div>Lysophosphatidic acid (LPA) is a small bioactive lysophospholipid that elicits diverse biological activities in bone homeostasis and diseases. However, the specific functions of LPA and intrinsic mechanism underlying these processes is not well understood. In this study, we identified that LPA regulated cell proliferation, migration, and osteogenic differentiation primarily via LPA₁ in MC3T3-E1 pre-osteoblastic cells. More importantly, western blot analysis indicated that LPA stimulated the activation of the transcriptional regulator YAP via the Hippo pathway kinases LATS, but had negligible effects on MST. Moreover, verteporfin was applied to block YAP, which further elucidated the effects of LPA-induced YAP activation on osteogenesis. Interestingly, Rho-kinase (ROCK) might also be involved in LPA-induced YAP nuclear localization and dephosphorylation. Taken together, these data provide novel insights into the molecular mechanisms of LPA in bone homeostasis and regeneration.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103111"},"PeriodicalIF":2.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933240","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":"Aqueous extracts of propolis modulate ECM remodeling and calcium levels during pre-osteoblast differentiation","authors":"Paula Bertin de Morais ,&nbsp;Gerson Santos de Almeida ,&nbsp;Ricardo de Oliveira Orsi ,&nbsp;Willian Fernando Zambuzzi ,&nbsp;Célio Jr. Da Costa Fernandes","doi":"10.1016/j.tice.2025.103101","DOIUrl":"10.1016/j.tice.2025.103101","url":null,"abstract":"<div><div>Osteoporosis and other bone-loss-related disorders remain major health concerns, underscoring the demand for innovative regenerative therapies. Propolis, a natural resinous substance rich in bioactive compounds such as caffeic acid phenethyl ester (CAPE), has emerged as a promising candidate for modulating bone regeneration. However, the cellular and molecular mechanisms underlying its effects on osteoblast function are not fully elucidated. In this study, we evaluated the impact of an aqueous extract of propolis on pre-osteoblast adhesion, proliferation, differentiation, extracellular matrix (ECM) remodeling, and inflammation. Our results showed that while propolis treatment did not alter cell adhesion or cytoskeletal organization, it significantly enhanced cell proliferation through the upregulation of CDK2 expression and phosphorylation, suggesting stimulation of G1/S cell cycle progression. Differentiation analyses demonstrated increased expression of osteogenic markers, including BMP7, Runx2, and Osterix, as well as modulation of the RankL/OPG axis. Despite limited mineralization, we observed enhanced collagen deposition and upregulation of ECM-related proteins, such as bone sialoprotein (BSP), alongside increased MMP9 activity, indicating active ECM remodeling. Moreover, propolis induced an anti-inflammatory cytokine profile, characterized by elevated IL-10 and reduced levels of pro-inflammatory cytokines IL-6, IL-18, and TNF-α. Altogether, our findings suggest that aqueous propolis extract promotes an osteogenic phenotype by modulating cell cycle progression, enhancing osteoblastic differentiation, remodeling the ECM, and reducing inflammation. These results support the potential use of propolis as a natural therapeutic agent in bone tissue engineering and regenerative medicine.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103101"},"PeriodicalIF":2.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920169","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":"Resveratrol-pretreated ADSC-CM alleviates liver oxidative damage in mice by mediating the Sirt1/Nrf2 axis","authors":"Jingwen Feng ,&nbsp;Chenhao Chang ,&nbsp;Ziqiang Zhang ,&nbsp;Leyao Hou,&nbsp;Yanni Zhong,&nbsp;Tianao Zhang,&nbsp;Qiongxia Lv,&nbsp;Dongliu Luo,&nbsp;Yumei Liu","doi":"10.1016/j.tice.2025.103099","DOIUrl":"10.1016/j.tice.2025.103099","url":null,"abstract":"<div><div>Chronic liver injury is a prevalent pathological condition. Adipose-derived stem cell-conditioned medium (CM) has demonstrated efficacy in attenuating liver injury. Resveratrol (Res) pretreatment enhances the therapeutic effect of ADSCs, but whether it can enhance the protective effect of CM against CCl₄-induced liver injury is unknown. Therefore, we investigated the effects of CM and Res-pretreated adipose-derived stem cell-conditioned medium (R-CM) on liver structure, fibrosis, proliferation, oxidative stress, and mitochondrial pathway apoptosis in CCl₄-injured mice and further explored the underlying regulatory mechanism of the antioxidant effects of Res on CM. These findings indicated that R-CM was more effective than CM in mitigating CCl₄-induced liver injury, fibrosis, oxidative stress, and apoptosis. Moreover, we found that Res enhances the antioxidant capacity of CM by mediating the Sirt1/Nrf2 axis. Overall, our study demonstrated that CM derived from ADSCs could alleviate CCl₄-induced hepatic oxidative stress, and we found that Res could increase the antioxidant capacity of CM, which is closely related to the regulation of the Sirt1/Nrf2 pathway.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103099"},"PeriodicalIF":2.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933241","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":"NLRP3 inflammasome activation in PCOS: A novel target for managing insulin resistance and metabolic dysregulation","authors":"Fatemeh Samadi Nasab ,&nbsp;Hanie Babei ,&nbsp;Mehrnaz Nayebzadeh ,&nbsp;Elahe Sadati ,&nbsp;Ziba Zahiri ,&nbsp;Tayebeh Esfidani ,&nbsp;Shabnam Forouzin ,&nbsp;Atoosa Etezadi","doi":"10.1016/j.tice.2025.103097","DOIUrl":"10.1016/j.tice.2025.103097","url":null,"abstract":"<div><div>In this comprehensive narrative review, we systematically examine the role of the NLRP3 inflammasome in the pathogenesis of polycystic ovary syndrome (PCOS) and evaluate its potential as a therapeutic target for managing insulin resistance. We performed literature searches in PubMed, Scopus, and Web of Science up to April 2025, using keywords including “PCOS,” “NLRP3 inflammasome,” “insulin resistance,” and “reproductive dysfunction.” Only peer-reviewed studies directly addressing inflammasome activation in PCOS were included, while articles lacking mechanistic or clinical relevance were excluded. PCOS is a highly prevalent and complex endocrine–metabolic disorder characterized by chronic low-grade inflammation, insulin resistance, and reproductive dysfunction, affecting millions of women globally. Despite its widespread impact, current treatments mainly address symptoms rather than underlying disease mechanisms, highlighting the urgent need for novel, targeted therapeutic approaches. Emerging evidence implicates the NLRP3 inflammasome as a central mediator linking immune activation, metabolic dysregulation, and ovarian pathology in PCOS. Activation of NLRP3 triggers release of IL-1β and IL-18, which impair insulin signaling, disrupt glucose homeostasis, and sustain systemic inflammation. Beyond metabolic effects, NLRP3-driven inflammation contributes to anovulation, follicular atresia, and hormonal imbalance. Interactions with mitochondrial dysfunction and endoplasmic reticulum stress further amplify cellular stress responses, accelerating disease progression. This review synthesizes current mechanistic insights into how NLRP3 activation drives both metabolic and reproductive impairments in PCOS, and highlights emerging therapeutic strategies—including pharmacological inhibitors, anti-inflammatory agents, and precision medicine approaches—aimed at disrupting the inflammatory–insulin resistance cycle. By elucidating these immunometabolic mechanisms, our findings support a shift from symptom-based management toward targeted, disease-modifying interventions, advancing precision medicine in women’s health.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103097"},"PeriodicalIF":2.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902385","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 critical role of METTL3-mediated m6A RNA methylation in orchestrating musculoskeletal development: Underlying mechanisms and therapeutic perspectives","authors":"Yuanzhong Liang,&nbsp;Yang Fan,&nbsp;Chang Liu","doi":"10.1016/j.tice.2025.103098","DOIUrl":"10.1016/j.tice.2025.103098","url":null,"abstract":"<div><div>The musculoskeletal system provides structural support and enables movement, relying on intricate developmental processes coordinated by transcriptional and post-transcriptional mechanisms. Among these, N⁶-methyladenosine (m⁶A) RNA methylation, catalyzed primarily by methyltransferase-like 3 (METTL3), has emerged as a crucial regulator of gene expression impacting cellular differentiation and function. This review synthesizes current evidence elucidating the indispensable role of METTL3-mediated m⁶A modification in musculoskeletal development. We detail how METTL3 governs key events in skeletal muscle cells, including satellite cell activation, myoblast proliferation and differentiation, myotube formation, and regeneration, through targeted methylation of mRNAs (e.g., MEF2C, MyoD, MNK2, ACVR2A) and non-coding RNAs (e.g., miRNAs, lncRNAs, circRNAs). Similarly, METTL3 critically regulates bone cell dynamics by directing the osteogenic differentiation of bone marrow stromal cells, osteoblast function, osteoclast differentiation and activity, and chondrocyte homeostasis. Disruption of METTL3 expression or function impairs both muscle and bone development and repair. This comprehensive analysis underscores METTL3 as a central epigenetic regulator coordinating musculoskeletal formation and maintenance. Furthermore, we discuss the significant translational potential of targeting METTL3 and its associated pathways for regenerative medicine strategies aimed at treating musculoskeletal injuries and disorders.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103098"},"PeriodicalIF":2.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890893","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":"Isovitexin accelerates diabetic wound repair via coordinated angiogenesis and collagen remodeling: Mechanistic insights from cellular and streptozotocin-induced SD rat models","authors":"Ting-ting Chen ,&nbsp;Li-qin Xu ,&nbsp;Zhi-gang Gao ,&nbsp;Wei-wei Zhou ,&nbsp;Yan Ying","doi":"10.1016/j.tice.2025.103100","DOIUrl":"10.1016/j.tice.2025.103100","url":null,"abstract":"<div><div>Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, vascular insufficiency, and impaired tissue remodeling, leading to poor healing outcomes. The PI3K/Akt/eNOS signaling pathway is critical for regulating angiogenesis, apoptosis, and extracellular matrix organization—key processes disrupted in diabetic wounds. Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. However, its therapeutic potential and mechanistic action in diabetic wounds, particularly regarding multi-targeted regulation of angiogenesis, collagen deposition, and apoptosis within the complex wound microenvironment, remain unexplored. This study demonstrates that isovitexin accelerates diabetic wound healing. Using streptozotocin-induced diabetic rodent models and cell culture, we found isovitexin significantly promoted angiogenesis and vascular maturation, reduced oxidative damage and apoptosis, and improved collagen organization versus controls. Crucially, these effects were entirely abolished by the eNOS inhibitor L-NAME, confirming PI3K/Akt/eNOS pathway specificity. Whereas previous studies have largely focused on single-pathway interventions for diabetic wounds, the concurrent modulation of angiogenesis, matrix remodeling, and apoptosis remains unexplored. Our study uniquely demonstrates that isovitexin activates the PI3K/Akt/eNOS pathway to synchronously enhance angiogenesis, promote collagen maturation, and inhibit apoptosis. This tripartite mechanism—uncovered for the first time—provides a novel therapeutic strategy to address the multifactorial pathology of diabetic wounds. Future research should prioritize clinical translation of these findings.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103100"},"PeriodicalIF":2.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913285","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":"Ultrasonic irradiation for ZnO NPs Synthesis and their hepatoprotective effect against acetaminophen induced hepatic toxicity in albino rats: Biochemical, physiological, and histopathological assessments","authors":"Yasmine A. Mansour ,&nbsp;Fady Sayed Youssef ,&nbsp;Shaymaa Hussein ,&nbsp;Hanan F. AbdEl_Halim ,&nbsp;Sameh H. Ismail ,&nbsp;Gehad G. Mohamed ,&nbsp;Abdelfattah M. Abdelfattah ,&nbsp;Rasha M.M. Ezz-Eldin ,&nbsp;Heba H. Mahboub ,&nbsp;Sherin Ibrahim","doi":"10.1016/j.tice.2025.103095","DOIUrl":"10.1016/j.tice.2025.103095","url":null,"abstract":"<div><div>The present novel trial assesses the prophylactic influence of ZnO NPs in comparison to silymarin against liver damage induced by acetaminophen (APAP). Forty albino rats were allocated into 4 groups (n = `10 rats/ group). Group I (Control), was orally administered 0.9 % NaCl for 21 days. Group II (exposed to APAP) received distilled water (1 ml/kg per day) via oral gavage for 19 successive days followed by APAP (600 mg/kg, PO) twice daily for 2 days. Group III (APAP+ Silymarin) was orally administered silymarin at the dose of 200 mg/kg daily for 19 days followed by APAP (600 mg/kg) via oral gavage twice daily for 2 successive days. Group IV (APAP+ ZnO NPs) was orally given ZnO NPs at the dose of 100 mg/kg daily for 19 days followed by (600 mg/kg/ twice daily) APAP orally for 2 successive days. APAP exhibited a substantial elevation of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, nitric oxide and malondialdehyde levels. Meanwhile, APAP markedly decreased catalase, SOD, GST and TAC levels. A significant elevation in DNA damage inside hepatocytes was noticed. APAP induced many histopathological changes. Conversely, the prophylactic use of ZnO NPs inhibited the elevation of AST, ALT, ALP, NO and MDA as well as the decline of catalase, SOD, GST and TAC levels induced by APAP toxicity compared to group III. Marked improvement of the architecture of hepatic tissue was noticed in group IV. In conclusion, ZnO-NPs were more actual in ameliorating APAP hepatotoxicity compared to silymarin via antioxidant and antiapoptotic pathways.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"98 ","pages":"Article 103095"},"PeriodicalIF":2.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922962","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":"ATF5 inhibits autophagy and the Wnt/β-catenin pathway by upregulating mTOR to suppress the stemness of liver cancer stem cells","authors":"Jie Jiang ,&nbsp;Xiangfang Li ,&nbsp;Huangyan Zhang ,&nbsp;Wei Liu ,&nbsp;Chunhai Hu ,&nbsp;Zongqiang Hu","doi":"10.1016/j.tice.2025.103094","DOIUrl":"10.1016/j.tice.2025.103094","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, and cancer stem cells (CSCs) are considered risk factors for HCC progression. Research has indicated a link between reduced ATF5 expression and the aggressive growth of HCC, yet the effect of ATF5 on the stemness of HCC is still ambiguous. Therefore, the aim of this study is to explore the role and potential mechanism of ATF5 in the stemness of HCC.</div></div><div><h3>Methods</h3><div>HCC clinical specimens were used to identify ATF5 expression and assess its correlation with HCC stemness. The expression of key genes and proteins was detected using RT<img>qPCR, western blotting and immunofluorescence. The cell phenotypes were detected by flow cytometry. The effects of ATF5 overexpression on the stemness of HCC cells were explored by tumor sphere formation and colony formation assays.</div></div><div><h3>Results</h3><div>Our research revealed that ATF5 levels were downregulated in HCC, whereas the level of the CSC marker CD133 was upregulated. In addition, ATF5 expression was negatively correlated with that of CD133. After ATF5 overexpression in Huh7 and Hep3B cells, the expression levels of the stemness-related markers CD133, EpCAM, NANOG, OCT4 and SOX2 in HCC cells decreased, and the sphere-forming and colony formation abilities also decreased, indicating that ATF5 is a negative regulatory factor of HCC stemness. In vivo animal experiments further demonstrated that ATF5 inhibits tumor growth and the stemness of cancer stem cells in vivo. From a mechanistic standpoint, ATF5 suppresses autophagy by increasing mTOR expression and suppressing Wnt/β-catenin pathway activation, thereby suppressing the stemness of HCC cells.</div></div><div><h3>Conclusion</h3><div>Our research revealed that ATF5 can inhibit the stemness of HCC cells, laying the foundation for the development of new therapies for HCC.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"97 ","pages":"Article 103094"},"PeriodicalIF":2.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902386","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}