International Journal of Biological Sciences最新文献_第10页

Cgref1 is a CREB-H-regulated hepatokine that promotes hepatic de novo lipogenesis by mediating epididymal fat insulin resistance. Cgref1是一种creb - h调节的肝因子，通过介导附睾脂肪胰岛素抵抗促进肝脏新生脂肪生成。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.97008

Pearl Chan, Pak-Hin Hinson Cheung, Xiao-Zhuo Kang, Yun Cheng, Chi-Ming Wong, Dong-Yan Jin, Chi-Ping Chan

{"title":"Cgref1 is a CREB-H-regulated hepatokine that promotes hepatic de novo lipogenesis by mediating epididymal fat insulin resistance.","authors":"Pearl Chan, Pak-Hin Hinson Cheung, Xiao-Zhuo Kang, Yun Cheng, Chi-Ming Wong, Dong-Yan Jin, Chi-Ping Chan","doi":"10.7150/ijbs.97008","DOIUrl":"https://doi.org/10.7150/ijbs.97008","url":null,"abstract":"Rationale: Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD) are interrelated metabolic disorders that pose significant health concerns. Hepatokines and other regulatory factors implicated in these diseases are incompletely understood. Here, we report on a new hepatokine named cell growth regulator with EF-hand domain 1 (Cgref1) that modulates lipid metabolism to aggravate these conditions. Methods: Cgref1 was identified by microarray analysis of downregulated genes in liver of Creb3l3 -/- mice. Cgref1 -/- mice were subjected to transcriptomic, metabolomic and lipidomic analyses as well as metabolic assays. Gain-of-function and loss-of-function assays were performed in primary hepatocytes and cultured human and mouse cells. Results: Cgref1 expression is induced by hepatic transcription factor CREB-H. Secreted Cgref1 primarily targets epididymal white adipose tissue (eWAT), where insulin signalling and glucose uptake are suppressed. Cgref1-/- mice showed lower tendencies of developing obesity, hyperglycaemia and dyslipidaemia, associated with compromised hepatic de novo lipogenesis. Thus, Cgref1 poses an advantage to maintain the normal functioning of vital organs by preserving glucose from being absorbed into eWAT. However, in circumstances where Cgref1 expression becomes excessive, eWAT develops insulin resistance, which in turn promotes hepatic glucose production, lipogenesis and MASLD development. Conclusion: As a hepatokine that affects blood glucose levels and lipogenesis, Cgref1 is a potential target in the intervention of metabolic disorders.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2568-2588"},"PeriodicalIF":8.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992103","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

EMC2 promotes breast cancer progression and enhances sensitivity to PDK1/AKT inhibition by deubiquitinating ENO1. EMC2促进乳腺癌进展，并通过去泛素化ENO1增强对PDK1/AKT抑制的敏感性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.109192

Shihan Xiao, Shangxuan Jiang, Chengxu Wen, Han Wang, Wenxiang Nie, Jianguo Zhao, Bo Zhang

{"title":"EMC2 promotes breast cancer progression and enhances sensitivity to PDK1/AKT inhibition by deubiquitinating ENO1.","authors":"Shihan Xiao, Shangxuan Jiang, Chengxu Wen, Han Wang, Wenxiang Nie, Jianguo Zhao, Bo Zhang","doi":"10.7150/ijbs.109192","DOIUrl":"https://doi.org/10.7150/ijbs.109192","url":null,"abstract":"Breast cancer is the most common malignant tumor worldwide, causing 685,000 deaths in 2020, and this number continues to rise. Identifying the molecular mechanisms driving breast cancer progression and potential therapeutic targets are currently urgent issues. Our previous work and bioinformatics analysis shows that the expression of Endoplasmic Reticulum Membrane Protein Complex Subunit 2 (EMC2) is up-regulated in breast cancer and is correlated with shortened overall survival of patients. However, the mechanism of EMC2 in breast cancer is yet to be elucidated. In this study, we identified that EMC2 promotes breast cancer proliferation and metastasis by activating the PDK1/AKT (T308)/mTOR (S2448) signaling pathway and can serve as a candidate target for PDK1/AKT inhibition. Mechanistically, EMC2 serves as a \"scaffold\" protein to recruit the deubiquitinating enzyme (DUB) USP7 for ENO1 deubiquitylation to stabilize its expression, thereby initiating downstream B-MYB/PDK1/AKT (T308)/mTOR (S2448) signal cascade. Silencing EMC2 significantly weaken the proliferation/metastasis potential of breast cancer in vitro and in vivo, but made tumor cell sensitive to PDK1/AKT inhibition. Overexpression of EMC2 leads to exactly the opposite result. This study reveals the EMC2/USP7/ENO1/B-MYB protumorigenic axis in breast cancer and identifies EMC2 as a candidate target for PDK1/AKT inhibitory therapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2629-2646"},"PeriodicalIF":8.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985739","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

Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects. 靶向糖酵解治疗乳腺癌耐药：目前进展和未来展望。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.109803

Zixu Niu, Jing He, Siyuan Wang, Bingjian Xue, Hao Zhang, Ruohan Hou, Zimeng Xu, Jing Sun, Fucheng He, Xinhong Pei

{"title":"Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.","authors":"Zixu Niu, Jing He, Siyuan Wang, Bingjian Xue, Hao Zhang, Ruohan Hou, Zimeng Xu, Jing Sun, Fucheng He, Xinhong Pei","doi":"10.7150/ijbs.109803","DOIUrl":"https://doi.org/10.7150/ijbs.109803","url":null,"abstract":"Breast cancer stands as one of the most prevalent malignant tumors threatening women's health and is a leading cause of cancer-related mortality. Its treatment faces significant challenges, including drug tolerance and disease recurrence. Glycolysis serves not only as a critical metabolic pathway for energy acquisition in breast cancer cells but also essentially promotes tumor proliferation, invasion, metastasis, and the development of resistance to therapy. Recent studies have revealed a close association between glycolytic reprogramming and drug resistance in breast cancer, with high-level glycolysis emerging as a hallmark of malignancy, deeply involved in the initiation and progression of tumors. This review summarizes recent advances in research on key enzymes and signaling pathways regulating glycolysis within the bodies of breast cancer patients. It explores in depth these molecular mechanisms and their complex interaction networks, offering a fresh perspective on overcoming drug resistance in breast cancer. Moreover, it underscores the importance of developing specific inhibitors targeting key enzymes and regulators of glycolysis and suggests that combining such inhibitors with existing anticancer drugs could substantially enhance therapeutic outcomes for breast cancer patients and reduce the occurrence of drug resistance.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2589-2605"},"PeriodicalIF":8.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979037","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

PSMG2 role in tumorigenesis and stemness mediated by protein accumulation, reticulum stress and autophagy. PSMG2在蛋白质积累、网络应激和自噬介导的肿瘤发生和干性中的作用。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105263

Asunción Espinosa-Sánchez, Elena Blanco-Alcaina, Amancio Carnero

{"title":"PSMG2 role in tumorigenesis and stemness mediated by protein accumulation, reticulum stress and autophagy.","authors":"Asunción Espinosa-Sánchez, Elena Blanco-Alcaina, Amancio Carnero","doi":"10.7150/ijbs.105263","DOIUrl":"https://doi.org/10.7150/ijbs.105263","url":null,"abstract":"The analysis of the dedifferentiation process has suggested that differentiated tumor cells undergo transformation toward cancer stem cells, accompanied by an increase in resistance to current chemotherapeutic treatments. Head and neck cancer (HNSCC) is a tumor with a high incidence and bad prognosis, and it is necessary to identify genes with alterations that can be explored therapeutically. PSMG2 is a chaperone protein that forms a heterodimer with PSMG1 and promotes the assembly of the 20S proteasome. Here, we characterized the effect of PSMG2 downregulation on tumorigenesis and the dedifferentiation process in head and neck cancer cell lines. We observed that high PSMG2 levels are associated with poor prognosis and survival in patients with HNSCC. Knockdown of PSMG2 reduced proliferation in vitro and in vivo in HNSCC cell lines. Moreover, the downregulation of PSMG2 diminished stemness, dedifferentiation and reprogramming properties. The reduction in PSMG2 levels caused the accumulation of polyubiquitinated proteins, increasing endoplasmic reticulum (ER) stress and activating apoptosis and autophagy as compensatory mechanisms. Furthermore, the response to proteasome inhibitors was increased in low-level PSMG2 patients. Therefore, PSMG2 is implicated in the assembly of the proteasome, which regulates ER stress as an essential cellular mechanism and autophagy and apoptosis as compensatory mechanisms for cellular homeostasis. PSMG2, and by extension the proteasome, is involved in cellular reprogramming and stemness.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2531-2549"},"PeriodicalIF":8.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017657","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

Targeting HCG18 counteracts ferroptosis resistance via blocking the miR-30a-5p/RRM2/GSS pathway in hepatocellular carcinoma. 靶向HCG18通过阻断肝细胞癌中miR-30a-5p/RRM2/GSS通路来抵消铁下垂耐药性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104127

Tian Zhan, Yawei Liu, Shuoke Duan, Chen Lu, Heng Jia, Ming Jin, Jie Li, Xinru Du, Sizheng Sun, Yuan Li, Jianping Zhang

{"title":"Targeting HCG18 counteracts ferroptosis resistance via blocking the miR-30a-5p/RRM2/GSS pathway in hepatocellular carcinoma.","authors":"Tian Zhan, Yawei Liu, Shuoke Duan, Chen Lu, Heng Jia, Ming Jin, Jie Li, Xinru Du, Sizheng Sun, Yuan Li, Jianping Zhang","doi":"10.7150/ijbs.104127","DOIUrl":"https://doi.org/10.7150/ijbs.104127","url":null,"abstract":"Background: Finding effective strategies and novel targets for reversing drug resistance is one of the major frontiers in hepatocellular carcinoma (HCC) research. Ferroptosis is participate in the malignant progression and drug resistance of HCC. However, the underlying molecular mechanisms remail largely uninvestigated. Methods: HCC cell lines and xenografted nude mice were used as experimental models. Biological functions were investigated by various molecular biology experiments. An HCC population was used to reveal clinical significance. Results: In our study, HCG18 and RRM2 was found to be associated with unfavorable prognosis. HCG18 regulates RRM2 expression through competitively binding to miR-30a-5p, consequently impacting ferroptosis. RRM2 directly regulated GSS to increase GSH synthesis. The colony formation assay demonstrated that overexpression of HCG18 inhibited erastin-induced cell death. In addition, in vivo experiments have also confirmed that HCG18 can inhibit ferroptosis by regulating the expression of RRM2, thereby promoting HCC proliferation. Conclusion: Our study discovered a novel lncRNA HCG18, as a \"switch-like\" molecule of the axis of miR-30a-5p/RRM2/GSS, confers resistance to ferroptosis and holds promise as a potential target for ferroptosis-dependent therapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2550-2567"},"PeriodicalIF":8.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986490","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

HDC/histamine Signaling Axis Drives Macrophage Reprogramming to Promote Angiogenesis in Hindlimb-Ischemic Mice. HDC/组胺信号轴驱动巨噬细胞重编程促进后肢缺血小鼠血管生成

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105148

Dili Sun, Jianfu Zhu, Gaofeng Zeng, Xiyang Yang, Xiaowei Zhu, Diyaerjiang Aierken, Zhaocheng Shi, Suling Ding, Junbo Ge, Hai Hu, Xiangdong Yang

{"title":"HDC/histamine Signaling Axis Drives Macrophage Reprogramming to Promote Angiogenesis in Hindlimb-Ischemic Mice.","authors":"Dili Sun, Jianfu Zhu, Gaofeng Zeng, Xiyang Yang, Xiaowei Zhu, Diyaerjiang Aierken, Zhaocheng Shi, Suling Ding, Junbo Ge, Hai Hu, Xiangdong Yang","doi":"10.7150/ijbs.105148","DOIUrl":"https://doi.org/10.7150/ijbs.105148","url":null,"abstract":"Histamine is catalyzed by histidine decarboxylase (HDC), which plays important roles in many physiological and pathological processes, but its role in angiogenesis has not been thoroughly clarified. Here we report that HDC is highly expressed in Ly6C+ macrophages, rather than in endothelial cells using Hdc-GFP transgenic mice with hindlimb ischemia (HLI) mouse model. Given the whole-process promoting effect of macrophages on angiogenesis, a cluster of HDC+CXCR2+ macrophages have been identified by single-cell sequencing technology in ischemic tissue. The inactivation of HDC leads to a lack of histamine and pro-angiogenic factor production in macrophages, inducing a harsh inflammatory microenvironment that is not conducive to the interaction between macrophages and endothelial cells. Moreover, HA-DA@histamine hydrogel has been designed and demonstrated to safely treat ischemic injury by modulating inflammation and angiogenesis. These data highlight the critical roles of HDC/histamine signaling in macrophage differentiation, angiogenesis, and muscle regeneration in the early stage of HLI.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2508-2530"},"PeriodicalIF":8.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978267","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

PROTAC-Surufatinib Suppresses Pancreatic Neuroendocrine Neoplasms Progression by Inducing Ferroptosis through Inhibiting WNT/β-catenin Pathway Mediated by HMOX1. PROTAC-Surufatinib通过抑制HMOX1介导的WNT/β-catenin通路诱导铁凋亡抑制胰腺神经内分泌肿瘤进展

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.106357

Bingyan Xue, Lijun Yan, Mujie Ye, Danyang Gu, Jianqiang Qian, Na He, Ping Hu, Feiyu Lu, Xintong Lu, Min Liu, Lin Xu, Jianan Bai, Yan Wang, Guoqin Zhu, Qiyun Tang

{"title":"PROTAC-Surufatinib Suppresses Pancreatic Neuroendocrine Neoplasms Progression by Inducing Ferroptosis through Inhibiting WNT/β-catenin Pathway Mediated by HMOX1.","authors":"Bingyan Xue, Lijun Yan, Mujie Ye, Danyang Gu, Jianqiang Qian, Na He, Ping Hu, Feiyu Lu, Xintong Lu, Min Liu, Lin Xu, Jianan Bai, Yan Wang, Guoqin Zhu, Qiyun Tang","doi":"10.7150/ijbs.106357","DOIUrl":"https://doi.org/10.7150/ijbs.106357","url":null,"abstract":"The small-molecule targeting drug Surufatinib is a new strategy for pancreatic neuroendocrine neoplasms (pNENs). However, the adverse reactions of Surufatinib should not be ignored in clinical practice. Based on PROTAC technology, we developed a novel tyrosine kinase (TK) degrader PROTAC-Surufatinib (hereinafter referred to as P-Surufatinib). This study was designed to investigate the effects and underlying mechanism of P-Surufatinib on pNENs. In vitro, we revealed that P-Surufatinib could more effectively inhibit proliferation and angiogenesis, and degrade target proteins in pNENs cells than Surufatinib. The transcriptome sequencing revealed that HMOX1 was the key molecule of P-Surufatinib to inhibit proliferation in pNENs. It was demonstrated that HMOX1 was lowly expressed in pNENs, and P-Surufatinib could up-regulate the expression of HMOX1 in pNENs. Mechanistically, P-Surufatinib inhibited pNENs progression by inducing ferroptosis through the suppression of HMOX1 mediated WNT/β-catenin signaling pathway. In vivo, P-Surufatinib could obviously suppress the growth of subcutaneous tumors in nude mice and enhance the expressional level of HMOX1 in tumorous tissue. In summary, our findings reveal that P-Surufatinib can suppress pNENs progression via inducing ferroptosis through up-regulating the expressional level of HMOX1 by inhibiting WNT/β-catenin signaling pathway, which provides a novel treatment method for pNENs.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2476-2492"},"PeriodicalIF":8.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007331","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

Antcin K ameliorates cardiotoxin-induced skeletal muscle injury and inflammation via IL-10 regulation. 抗霉素K通过调节IL-10改善心脏毒素诱导的骨骼肌损伤和炎症。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.107343

Ting-Kuo Chang, Lin-Chu Huang, Yueh-Hsiung Kuo, Chun-Hao Tsai, Hsien-Te Chen, Yi-Syuan Wu, Chih-Hsin Tang, Chen-Ming Su

{"title":"Antcin K ameliorates cardiotoxin-induced skeletal muscle injury and inflammation via IL-10 regulation.","authors":"Ting-Kuo Chang, Lin-Chu Huang, Yueh-Hsiung Kuo, Chun-Hao Tsai, Hsien-Te Chen, Yi-Syuan Wu, Chih-Hsin Tang, Chen-Ming Su","doi":"10.7150/ijbs.107343","DOIUrl":"https://doi.org/10.7150/ijbs.107343","url":null,"abstract":"Background: Skeletal muscle, functioning as an endocrine organ, produces a variety of molecules that contribute to the pathophysiology of sarcopenia, leading to muscular injury and inflammation. Antcin K, a bioactive compound derived from Antrodia cinnamomea and used in traditional Chinese medicine for its anti-inflammatory properties, was evaluated in this study with the aim of assessing its effects on resisting the progression of sarcopenia both in vitro and in vivo. Methods: Cardiotoxin (CTX)-induced muscle injury and the treatment of Antcin K in C2C12 cells were both used for RNA sequencing and ingenuity pathway analysis. We also stably cloned an IL-10 knockdown (IL-10-/+) C2C12 cell line for the effects of Antcin K treatment on CTX-induced muscle injury. CTX-induced muscle injury in a mouse model. Results: Antcin K ameliorated the CTX-induced muscle injury and inflammation in myoblasts and differentiated myocytes. Bioinformatics analysis results demonstrated the ability of Antcin K to modulate inflammation and enhance myogenesis via upregulated IL-10. Antcin K enhances IL-10 production via the PI3K/Akt signaling pathways. For the in vivo results, Antcin K protects against CTX-induced skeletal muscle inflammation and injury. Conclusion: Antcin K ameliorated CTX-induced muscle injury and inflammation through PI3K and Akt and upregulated IL-10 in vitro. The CTX-induced injury mouse model was rescued by intraperitoneal injection of Antcin k in vivo. Antcin K shows promise as a prospective candidate for the development of an innovative treatment for muscular injury, with significant implications for sarcopenia.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2493-2507"},"PeriodicalIF":8.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999212","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

A Novel Mouse Model of Depression: Advantages in Immune Research and Clinical Translation. 一种新的抑郁症小鼠模型：免疫研究和临床转化的优势。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104950

Jing Xiong, Xian-Qiang Zhang, Ji-Tao Li, Chi Ren, Tian Shen, Yun-Ai Su, Tian-Mei Si

{"title":"A Novel Mouse Model of Depression: Advantages in Immune Research and Clinical Translation.","authors":"Jing Xiong, Xian-Qiang Zhang, Ji-Tao Li, Chi Ren, Tian Shen, Yun-Ai Su, Tian-Mei Si","doi":"10.7150/ijbs.104950","DOIUrl":"https://doi.org/10.7150/ijbs.104950","url":null,"abstract":"The role of neuroimmune mechanisms in major depressive disorder (MDD) has been gradually highlighted, but existing classical animal models of MDD have limitations in immune inflammation research due to physical injury, high mortality rates, and immune tolerance. This study developed a novel mouse model of depression called the post-witness social defeat stress (PWSDS) model, which combines witness stress with the social defeat paradigm. The model was evaluated based on behavior, central and peripheral immune responses, and predictive validity. The findings revealed that PWSDS-exposed mice exhibited significant anxiety-like behavior, depressive-like behavior, cognitive deficits, and enhanced peripheral and central neuroimmune responses. Additionally, the antidepressant fluoxetine effectively ameliorated the depressive-like phenotypes and immune response in stressed mice. The model captured certain aspects of the behavioral and peripheral immune features of MDD patients. The levels of cortisol and proinflammatory cytokines such as TNFα in the serum of MDD patients with adult stressors increased compared with healthy controls, and were alleviated by SSRIs treatment, accompanied by improvement in depressive symptoms, anxiety symptoms and cognitive impairments. This study establishes an improved mouse model of MDD, which has specific advantages in immune research and offers a novel approach to further study the pathogenesis and new treatment of MDD.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2446-2461"},"PeriodicalIF":8.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979036","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

The SGK3/GSK3β/β-catenin signaling promotes breast cancer stemness and confers resistance to alpelisib therapy. SGK3/GSK3β/β-catenin信号通路促进乳腺癌的干性并赋予对alpelisib治疗的抗性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104850

Tingting Kang, Yuanfang Wang, Yaxin Jiang, Shunjie Chen, Na Lin, Minyan Guo, Haotu Zhu, Di Tang, Xiaofan Ding, Mian He

{"title":"The SGK3/GSK3β/β-catenin signaling promotes breast cancer stemness and confers resistance to alpelisib therapy.","authors":"Tingting Kang, Yuanfang Wang, Yaxin Jiang, Shunjie Chen, Na Lin, Minyan Guo, Haotu Zhu, Di Tang, Xiaofan Ding, Mian He","doi":"10.7150/ijbs.104850","DOIUrl":"https://doi.org/10.7150/ijbs.104850","url":null,"abstract":"Drug resistance is the leading cause of death in patients with advanced tumors. Alpelisib, a selective PIK3CA inhibitor, has been recently approved for treating advanced breast cancer. However, drug resistance is inevitable, and the mechanisms behind alpelisib-associated resistance remain elusive. To address this problem, we established an alpelisib-resistant breast cancer cell model and confirmed that the resistant cells exhibited enhanced abilities in colony formation, migration, anti-apoptosis, spheroidization, tumor formation and metastasis. Further analysis revealed that SGK3 was significantly upregulated in alpelisib-resistant cells, which was strongly associated with tumor stemness. Additionally, we observed that SGK3 promoted tumor cell stemness by activating GSK3β/β-catenin signaling pathway, leading to the resistance to alpelisib in breast cancer. Finally, we demonstrated that SGK3 inhibitor could restore the sensitivity of resistant cells to alpelisib. Collectively, these findings suggest that SGK3 could be a novel therapeutic target for breast cancer patients who developed resistance to alpelisib.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 6","pages":"2462-2475"},"PeriodicalIF":8.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986354","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