International Journal of Biological Sciences最新文献_第8页

Heat acclimation mediates cellular protection via HSP70 stabilization of HIF-1α protein in extreme environments. 在极端环境下，热驯化通过HIF-1α蛋白的HSP70稳定化介导细胞保护。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.103122

Can Li, Jirui Wen, Ling Wang, Jun Lei, Zhengdong Lin, Yuhao Zou, Juan Cheng, Xuehong Wan, Jifeng Liu, Jiang Wu

{"title":"Heat acclimation mediates cellular protection via HSP70 stabilization of HIF-1α protein in extreme environments.","authors":"Can Li, Jirui Wen, Ling Wang, Jun Lei, Zhengdong Lin, Yuhao Zou, Juan Cheng, Xuehong Wan, Jifeng Liu, Jiang Wu","doi":"10.7150/ijbs.103122","DOIUrl":"10.7150/ijbs.103122","url":null,"abstract":"Heat acclimation (HA) is an evolutionarily conserved trait that enhances tolerance to novel stressors by inducing heat shock proteins (HSPs). However, the molecular mechanisms underlying this phenomenon remain elusive. In this study, we established a HA mouse model through intermittent heat stimulation. Subsequently, this model was evaluated using an array of physiological and histological assessments. In vitro, HA cell model with mouse brain microvascular endothelial cells (bEnd.3) was established and analyzed for cell viability and apoptosis markers. We investigated HA-mediated heat and hypoxia tolerance mechanisms using HIF-1α and HSP70 inhibitors and siRNA. Our results demonstrated that HA enhances the tolerance of bEnd.3 cells and mice to both heat and hypoxia, Mechanistically, HA upregulated the expression of HIF-1α and HSP70. However, inhibition of HIF-1α or HSP70 partially attenuated HA-induced tolerance to heat and hypoxia. Additionally, HA significantly decreased the ubiquitination levels of HIF-1α, whereas inhibition of HSP70 increased its ubiquitination. HA also substantially enhanced the interaction between HIF-1α and HSP70. In conclusion, our findings indicate that HA enhances tolerance to heat and hypoxia by stabilizing HIF-1α through increased interaction with HSP70. This discovery elucidates a novel mechanism of cellular protection conferred by HA and provides new strategies and potential targets for human adaptation to extreme environments.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 1","pages":"175-188"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Smad2 Cooperating with TGIF2 Contributes to EMT and Cancer Stem Cells Properties in Pancreatic Cancer via Co-Targeting SOX2. Smad2与TGIF2合作通过共同靶向SOX2影响胰腺癌的EMT和癌症干细胞特性

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.102381

Fuqiang Zu, ChuanPing Chen, Qilong Geng, Haoyu Li, Boyuan Chan, Guopei Luo, Mengcheng Wu, Matthias Ilmer, Bernhard W Renz, Lutterodt Bentum-Ennin, Hao Gu, Weiwei Sheng

{"title":"Smad2 Cooperating with TGIF2 Contributes to EMT and Cancer Stem Cells Properties in Pancreatic Cancer via Co-Targeting SOX2.","authors":"Fuqiang Zu, ChuanPing Chen, Qilong Geng, Haoyu Li, Boyuan Chan, Guopei Luo, Mengcheng Wu, Matthias Ilmer, Bernhard W Renz, Lutterodt Bentum-Ennin, Hao Gu, Weiwei Sheng","doi":"10.7150/ijbs.102381","DOIUrl":"https://doi.org/10.7150/ijbs.102381","url":null,"abstract":"The underlying mechanisms between cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) remain unclear. In this study, we identified TGIF2 as a target gene of CSC using sncRNA and machine learning. TGIF2 is closely related to the expression of SOX2, EGFR, and E-cadherin, indicating poor prognosis. Mechanistically, TGIF2 promoted the EMT phenotype and CSC properties following the activation of SOX2, Slug, CD44, and ERGF/MAPK signaling, which were rescued by SOX2 silencing. TGIF2 silencing contributes to the opposite phenotype via SOX2. Notably, Smad2 cooperates with TGIF2 to co-regulate the SOX2 promoter, which in turn promotes EMT and CSC signaling by transactivating Slug and EGFR, respectively. The transactivation of EGFR/MAPK signaling by SOX2 promotes TGIF2 nuclear translocation, forming a positive feedback loop in vitro. Moreover, the interaction of TGIF2 and SOX2 with EGFR inhibitors promoted subcutaneous tumors and liver metastasis in vivo. Thus, the TGIF2/SOX2 axis contributes to CSC, EMT, and chemoresistance, providing a promising target for PC therapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"524-543"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells. 低温大气血浆通过EGFR（Y1068）介导的GPX4双轴增强三阴性乳腺癌细胞中的铁下垂。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.105455

Xiaofeng Dai, Ziyao Xu, Xinyu Lv, Chao Li, Ruichen Jiang, Danjun Wang, Ming Xi, Tian Li

{"title":"Cold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells.","authors":"Xiaofeng Dai, Ziyao Xu, Xinyu Lv, Chao Li, Ruichen Jiang, Danjun Wang, Ming Xi, Tian Li","doi":"10.7150/ijbs.105455","DOIUrl":"10.7150/ijbs.105455","url":null,"abstract":"Cold atmospheric plasma (CAP) has been proposed as an emerging onco-therapeutics that can specifically kill cancer cells without harming healthy cells. Here we explore its potency in triggering ferroptosis in transformed cells using triple negative breast cancer as the disease model. Through the whole transcriptome sequencing, mass spectrometry analysis, point mutation, and a series of in vitro and in vivo molecular assays, we identified two signaling axes centered at EGFR(Y1068), i.e., EGFR-TRIM25-KEAP1/SIAH2-NRF2 and EGFR-p38-NRF2, which suppressed GPX4 at both transcriptional and translational levels. We, in addition, demonstrated the potency of CAP in synergizing with Sorafenib towards enhanced selectivity against cancer cells via initiating ferroptosis. We are the first to systematically clarify the molecular mechanism of GPX4-dependent ferroptosis induced by CAP, and propose the feasibility of activating EGFR instead of suppressing it as well as the benefits of resolving tumors by coupling CAP with ferroptosis-inducing agents. The identified signaling axis is applicable to all cancers harboring EGFR that deserve intensive investigations.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"874-892"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Helicobacter Pylori-induced BRD2 m⁶A modification sensitizes gastric cancer cells to chemotherapy by breaking FLIP/Caspase-8 homeostasis. 幽门螺杆菌诱导的BRD2 m6A修饰通过打破FLIP/Caspase-8稳态使胃癌细胞对化疗敏感。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.97464

Sen Wang, Zhe Xuan, Zetian Chen, Penghui Xu, Lang Fang, Zheng Li, Yigang Zhang, Hongda Liu, Linjun Wang, Diancai Zhang, Hao Xu, Li Yang, Zekuan Xu

{"title":"Helicobacter Pylori-induced BRD2 m6A modification sensitizes gastric cancer cells to chemotherapy by breaking FLIP/Caspase-8 homeostasis.","authors":"Sen Wang, Zhe Xuan, Zetian Chen, Penghui Xu, Lang Fang, Zheng Li, Yigang Zhang, Hongda Liu, Linjun Wang, Diancai Zhang, Hao Xu, Li Yang, Zekuan Xu","doi":"10.7150/ijbs.97464","DOIUrl":"10.7150/ijbs.97464","url":null,"abstract":"Background: Chemoresistance severely deteriorates the prognosis of advanced gastric cancer (GC) patients. Several studies demonstrated that H. pylori (HP)-positive GC patients showed better outcomes after receiving chemotherapy than HP-negative ones. This study aims to confirm the role of HP in GC chemotherapy and to study the underlying mechanisms. Methods: The HP infection co-culture with GC cell lines were performed. The m6A-seq and NGS were used for bioinformatic analysis. Western Blot, qRT-PCR and IHC were adopted for expressions of METTL3, BRD2 and YTHDF2. The ATPGlow, flow cytometry and IF were used to detect the cell viability, DNA damage, apoptosis and pyroptosis. Luciferase reporter assay and CHIP were applied to explore the mechanisms. Results: The HP infection sensitized GC cells to 5-FU and induced expressions of METTL3 and YTHDF2. The HP infection promoted transcription of METTL3 through NF-κB pathway, therefore promoting the m6A modification level. METTL3 induced the m6A modification of BRD2 while YTHDF2 promoted the decay of mRNA of BRD2, both of which could promote the apoptosis and pyroptosis induced by 5-FU. In addition, BRD2 regulated the transcription of FLIP by importing FOXO4 into nucleus, thereby inhibiting the activation of Caspase-8, which was considered as the molecular switch of both apoptosis and pyroptosis. Conclusions: HP-induced m6A methylation could sensitize gastric cancers to 5-FU with activation of caspase-8 and induced apoptosis and pyroptosis. The Methylated BRD2 activated by NF-κB pathway regulates Caspase-8 by binding to FLIP-promoter FOXO4. This study provides new sights to the HP-positive gastric cancer chemotherapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 1","pages":"346-362"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice. 老年小鼠麻醉和手术后海马中的Lingo1参与认知功能障碍。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.98376

Changliang Liu, Changteng Zhang, Ling Chen, Xin Liu, Jiahui Wu, Yalan Sun, Jin Liu, Chan Chen

{"title":"Lingo1 in the hippocampus contributes to cognitive dysfunction after anesthesia and surgery in aged mice.","authors":"Changliang Liu, Changteng Zhang, Ling Chen, Xin Liu, Jiahui Wu, Yalan Sun, Jin Liu, Chan Chen","doi":"10.7150/ijbs.98376","DOIUrl":"https://doi.org/10.7150/ijbs.98376","url":null,"abstract":"Cognitive impairment caused by anesthesia and surgery is one of the most common complications with multiple etiologies that occurs in elderly patients. The underlying mechanisms are not fully understood, and there is a lack of therapeutic strategies. Increasing evidence has demonstrated that myelin loss, abnormal phosphorylation of the tau protein and neuronal apoptosis are substantial driving factors of cognitive deficits. However, the key regulatory factors involved in the pathology of postoperative cognitive dysfunction require further investigation. Herein, we identified a key regulator, Lingo1, whose expression significantly increased in hippocampal neurons after aged mice underwent unilateral nephrectomy. Elevated Lingo1 expression markedly activated the RhoA/ROCK1 signaling pathway through interactions with NgR and p75NTR, subsequently promoting myelin loss and abnormal phosphorylation of the tau protein. Moreover, the upregulation of Lingo1 in hippocampal neurons further inhibited the EGFR/PI3K/Akt pathway, which may increase neuronal apoptosis. These pathological changes ultimately lead to cognitive impairment in aged mice after surgery. Notably, Lingo1 knockdown significantly reversed pathological changes in the hippocampus and attenuated cognitive decline. In conclusion, our findings highlight that Lingo1 upregulation in hippocampal neurons promotes the occurrence and development of postoperative cognitive dysfunction by regulating myelin loss, abnormal tau phosphorylation and neuronal apoptosis, suggesting that Lingo1 might be a potential target for treating postoperative cognitive dysfunction.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"595-613"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FAT1 knockdown enhances the CSC properties of HNSCC through p-CaMKII-mediated inactivation of the IFN pathway. FAT1敲低通过p- camkii介导的IFN通路失活增强HNSCC的CSC特性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.95723

Jingjing Wang, Yang Chen, Yunqing Sun, Hanzhe Liu, Ruixue Du, Xuewen Wang, Zhe Shao, Ke Liu, Zhengjun Shang

{"title":"FAT1 knockdown enhances the CSC properties of HNSCC through p-CaMKII-mediated inactivation of the IFN pathway.","authors":"Jingjing Wang, Yang Chen, Yunqing Sun, Hanzhe Liu, Ruixue Du, Xuewen Wang, Zhe Shao, Ke Liu, Zhengjun Shang","doi":"10.7150/ijbs.95723","DOIUrl":"https://doi.org/10.7150/ijbs.95723","url":null,"abstract":"FAT atypical cadherin 1 (FAT1), which encodes an atypical cadherin-coding protein, has a high mutation rate and is commonly regarded as a tumor suppressor gene in head and neck squamous cell carcinoma (HNSCC). Nonetheless, the potential regulatory mechanisms by which FAT1 influences the progression of HNSCC remain unresolved. In this context, we reported that FAT1 was downregulated in tumor tissues/cells compared with normal tissues/cells and that it was correlated with the clinicopathological features and prognosis of HNSCC. Knockdown of FAT1 enhanced cancer stem cell (CSC) properties and decreased the percentage of apoptotic tumor cells. Mechanistically, FAT1 knockdown increased the phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), subsequently resulting in diminished interaction between phosphorylated STAT1 and interferon regulatory factor 9 (IRF9), which inactivated the interferon pathway and facilitated the adoption of the malignant phenotype of HNSCC cells. The overexpression of STAT1 and IRF9 alleviated the malignant behavior caused by FAT1 inhibition. In summary, our study reveals the role of FAT1 in suppressing the CSC properties of HNSCC via the CaMKII/STAT1/IRF9 pathway, and that targeting FAT1 might be a promising treatment for HNSCC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"671-684"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY. HIF-2α/LPCAT1通过调节fbxw7介导的ACLY泛素化，协调ccRCC中脂质代谢的重编程。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.103032

Mintian Fei, Yi Zhang, Haolin Li, Qili Xu, Yu Gao, Cheng Yang, Weiyi Li, Chaozhao Liang, Baojun Wang, Haibing Xiao

{"title":"HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY.","authors":"Mintian Fei, Yi Zhang, Haolin Li, Qili Xu, Yu Gao, Cheng Yang, Weiyi Li, Chaozhao Liang, Baojun Wang, Haibing Xiao","doi":"10.7150/ijbs.103032","DOIUrl":"https://doi.org/10.7150/ijbs.103032","url":null,"abstract":"The current research revealed a strong link between lipid reprogramming and dysregulated lipid metabolism to the genesis and development of clear cell renal cell carcinoma (ccRCC). Pathologically, ccRCC exhibits a high concentration of lipid droplets within the cytoplasm. HIF-2α expression has previously been demonstrated to be elevated in ccRCC caused by mutations in the von Hippel-Lindau (VHL) gene, which plays a vital role in the development of renal cell carcinoma. Nevertheless, the mechanisms by which HIF-2α influences lipid metabolism reprogramming are unknown. Our investigation demonstrated that HIF-2α directly binds to the promoter region of LPCAT1, promoting its transcription. RNA-seq and lipidomics mass spectrometry studies showed that knocking down LPCAT1 significantly reduced triglyceride production. Research suggests that KD-LPCAT1 involves activation of the NF-κB signaling pathway, which activates F-Box/WD Repeat-Containing Protein 7 (FBXW7). FBXW7, an E3 ubiquitin ligase involved in lipid metabolism, interacts with ATP Citrate Lyase (ACLY) to promote its degradation, lowering fatty acid production and contributing to the lipid content reduction.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"614-631"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals. 用直接作用的抗病毒药物根除HCV后，小管间质性肾炎抗原样1促进肝纤维化进展。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.103305

Lei Lei, Hu Li, Xue-Kai Wang, Jian-Rui Li, Han Sun, Hong-Ying Li, Jia-Yu Li, Mei Tang, Jing-Chen Xu, Biao Dong, Yue Gong, Dan-Qing Song, Jian-Dong Jiang, Zong-Gen Peng

{"title":"Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.","authors":"Lei Lei, Hu Li, Xue-Kai Wang, Jian-Rui Li, Han Sun, Hong-Ying Li, Jia-Yu Li, Mei Tang, Jing-Chen Xu, Biao Dong, Yue Gong, Dan-Qing Song, Jian-Dong Jiang, Zong-Gen Peng","doi":"10.7150/ijbs.103305","DOIUrl":"https://doi.org/10.7150/ijbs.103305","url":null,"abstract":"Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs. Overexpression of TINAGL1 in the liver triggers and exacerbates liver fibrosis, and xenotransplantation of HCV-eradicated Huh7.5 cells leads to a higher risk of hepatocellular carcinoma. Conversely, knockdown of TINAGL1 expression prevents and attenuates the progression of liver fibrosis in mice. TINAGL1 binds and stabilizes platelet-derived growth factor-BB (PDGF-BB) in hepatocytes, leading to an increase in intracellular and extracellular PDGF-BB, which sensitizes the PDGF-BB/PDGFRβ pathway to activate hepatic stellate cells. This study highlights that TINAGL1 is a new factor contributing to liver fibrosis after injury, including but not limited to HCV infection, even after virological cure by DAAs, and emphasizes the therapeutic potential of TINAGL1 as an innovative target for the treatment of liver fibrosis.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"802-822"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BRAF-activated ARSI suppressed EREG-mediated ferroptosis to promote BRAF^V600E (mutant) papillary thyroid carcinoma progression and sorafenib resistance. braf激活的ARSI抑制ereg介导的铁下垂，促进BRAFV600E（突变体）乳头状甲状腺癌的进展和索拉非尼耐药性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.99423

Xing Chen, Xiang Chen, Wenjun Xie, Hua Ge, Hongyan He, Ailong Zhang, Junjie Zheng

{"title":"BRAF-activated ARSI suppressed EREG-mediated ferroptosis to promote BRAFV600E (mutant) papillary thyroid carcinoma progression and sorafenib resistance.","authors":"Xing Chen, Xiang Chen, Wenjun Xie, Hua Ge, Hongyan He, Ailong Zhang, Junjie Zheng","doi":"10.7150/ijbs.99423","DOIUrl":"10.7150/ijbs.99423","url":null,"abstract":"Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and patients with the BRAFV600E mutation often exhibit aggressive tumor behavior. Here, we identified Arylsulfatase I (ARSI) as a gene whose expression was significantly upregulated in BRAFV600E PTC and was associated with poor prognosis. High ARSI expression correlated with advanced disease stage, BRAF mutation, and worse overall survival in PTC patients. Functional studies revealed that ARSI promoted the tumor growth, cell migration, and epithelial-mesenchymal transition (EMT) of BRAFV600E PTC cells in vitro. In vivo studies confirmed that ARSI suppression inhibited tumor growth and metastasis in mouse models of PTC. Mechanistically, ARSI knockdown triggered ferroptosis in BRAFV600E-mutant PTC cells and sensitized PTC cells to sorafenib-induced ferroptosis. Epiregulin (EREG) was identified as a downstream target of ARSI and is regulated by STAT3 transcriptional activation. EREG overexpression rescued the ferroptosis resistance and malignant phenotypes induced by ARSI knockdown in BRAFV600E-mutant PTC cells. Finally, we constructed a prognostic signature and diagnostic model based on ARSI and EREG expression data, which demonstrated high predictive value for identifying high-risk PTC patients with the BRAFV600E mutation. Our study highlights the critical role of ARSI in promoting aggressive phenotypes and therapeutic resistance in BRAFV600E PTC through ferroptosis regulation. Targeting the ARSI-EREG axis may offer novel therapeutic avenues for improving outcomes in BRAFV600E PTC patients.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 1","pages":"128-142"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caveolin-1 mitigates the advancement of metabolic dysfunction-associated steatotic liver disease by reducing endoplasmic reticulum stress and pyroptosis through the restoration of cholesterol homeostasis. 小窝蛋白-1通过恢复胆固醇稳态，减少内质网应激和焦亡，从而减轻代谢功能障碍相关脂肪变性肝病的进展。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-01 DOI: 10.7150/ijbs.100794

Hanlin Xu, Yu Li, Ning Guo, Shuai Wu, Can Liu, Zhongxuan Gui, Weiju Xue, Xiangfu Jiang, Mengjia Ye, Qianqian Geng, Xiaowen Feng, Chao Zhang, Lei Jin, Chengmu Hu

{"title":"Caveolin-1 mitigates the advancement of metabolic dysfunction-associated steatotic liver disease by reducing endoplasmic reticulum stress and pyroptosis through the restoration of cholesterol homeostasis.","authors":"Hanlin Xu, Yu Li, Ning Guo, Shuai Wu, Can Liu, Zhongxuan Gui, Weiju Xue, Xiangfu Jiang, Mengjia Ye, Qianqian Geng, Xiaowen Feng, Chao Zhang, Lei Jin, Chengmu Hu","doi":"10.7150/ijbs.100794","DOIUrl":"https://doi.org/10.7150/ijbs.100794","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, which has the potential to advance to fibrosis. CAV1 has the effects of improving liver lipid deposition in MASLD, however, the potential mechanism is largely unknown. Here, we establish a MASLD mouse model in CAV1 knockout (KO) mice and perform transcriptome analysis on livers from mice to investigate the effects of CAV1 in MASLD progression. In addition, we evaluated the expression of CAV1 in human liver samples, and also conducted assays in vitro to investigate the molecular role of CAV1 in MASLD progression. The results illustrate that the expression of liver CAV1 in the decreases during MASLD progression, which aggravates the accumulation of cholesterol in the liver, leading to more severe endoplasmic reticulum (ER) stress and pyroptosis. Mechanistically, CAV1 regulates the expression of FXR/NR1H4 and its downstream cholesterol transporter, ABCG5/ABCG8, suppressing ER stress and alleviating pyroptosis. Our study confirms CAV1 is a crucial regulator of cholesterol homeostasis in MASLD and plays an important role in disease progression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 2","pages":"490-506"},"PeriodicalIF":8.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0