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Mogroside V restores glycolytic function via LDHA promoter demethylation independent of alternative splicing in PCOS granulosa cells 在PCOS颗粒细胞中,苦苷V通过LDHA启动子去甲基化恢复糖酵解功能,而不依赖于选择性剪接
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-28 DOI: 10.1016/j.jsbmb.2025.106839
Shuai Li , Jiaxin Wu , Renhong Lu , Benliang Zhou , Hongpeng Dai , Zhen Zhang , Xiaogan Yang , Xingwei Liang
{"title":"Mogroside V restores glycolytic function via LDHA promoter demethylation independent of alternative splicing in PCOS granulosa cells","authors":"Shuai Li ,&nbsp;Jiaxin Wu ,&nbsp;Renhong Lu ,&nbsp;Benliang Zhou ,&nbsp;Hongpeng Dai ,&nbsp;Zhen Zhang ,&nbsp;Xiaogan Yang ,&nbsp;Xingwei Liang","doi":"10.1016/j.jsbmb.2025.106839","DOIUrl":"10.1016/j.jsbmb.2025.106839","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by metabolic dysfunction. This study investigated whether Mogroside V (MV) ameliorates hyperandrogenism-induced glycolytic dysfunction in testosterone (TES)-treated KGN cells. KGN cells treated with 150 µM TES exhibited significantly reduced viability, decreased lactate production, and increased pyruvate levels, which were reversed by 60 µM MV. Transcriptomic analysis revealed that TES dysregulated gene expression associated with alternative splicing (AS) and glycolytic pathways, while MV normalized glycolysis-related genes (<em>LDHA</em>, <em>PKM</em>) without affecting AS events. Although TES upregulated splicing factors <em>HNRNPH3</em> and <em>SRSF1</em>, MV restored the expression of <em>HNRNPH3</em> and <em>SRSF1</em> without inducing aberrant splicing. Mechanistically, MV significantly reduced TES-induced hypermethylation of the <em>LDHA</em> promoter, thereby restoring <em>LDHA</em> mRNA and protein expression. MV mitigates PCOS-associated metabolic dysfunction primarily through <em>LDHA</em> promoter demethylation, independent of alternative splicing regulation. This study highlights MV as a natural compound with epigenetic regulatory potential for PCOS therapy.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106839"},"PeriodicalIF":2.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polycystic ovary syndrome: The role of granulosa cell proliferation and apoptosis in disease development 多囊卵巢综合征:颗粒细胞增殖和凋亡在疾病发展中的作用
IF 2.5 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-26 DOI: 10.1016/j.jsbmb.2025.106838
Yao Yi , Yu Zhong , Rui-Ning Liang , Cheng-Yi Liu , Yi-Feng Zhang , Yi-Xuan Zhang
{"title":"Polycystic ovary syndrome: The role of granulosa cell proliferation and apoptosis in disease development","authors":"Yao Yi ,&nbsp;Yu Zhong ,&nbsp;Rui-Ning Liang ,&nbsp;Cheng-Yi Liu ,&nbsp;Yi-Feng Zhang ,&nbsp;Yi-Xuan Zhang","doi":"10.1016/j.jsbmb.2025.106838","DOIUrl":"10.1016/j.jsbmb.2025.106838","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is the most prevalent ovarian endocrine disorder in infertile women and significantly impacts their health. Granulosa cell (GC) is the largest functional cell type in follicular development and plays a crucial role in follicle growth, differentiation, and maturation. Studies have shown that women with PCOS experience abnormal GC proliferation and apoptosis, which contribute to symptoms such as inflammation, irregular estrous cycles, hormonal imbalances, and follicular development arrest. These findings suggest that altered GC quantity is a key factor in the pathogenesis and progression of PCOS. Nevertheless, substantial inconsistencies exist in studies regarding GC number changes in PCOS follicles. To explore the underlying causes, we reviewed recent literature on GC proliferation and apoptosis in PCOS over the past years. This review identifies several potential causes contributing to these discrepancies, including overlooked follicular-phase-dependent effects on GC quantity, variations in GC sources (PCOS vs. non-PCOS, human vs. animal models, and human immortalized granulosa cells), and the lack of animal model validation, inadequate detection of relevant indicators, and unclear identification of vital influential factors. To address these issues, we propose several potential solutions to provide valuable insights into elucidating the roles of GC proliferation and apoptosis, their regulatory mechanisms, and potential therapeutic strategies in PCOS.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106838"},"PeriodicalIF":2.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vitamin D3 (cholecalciferol) is more efficacious than Vitamin D2 (ergocalciferol) at regulating calcium absorption and bone quality in rats 维生素D3(胆钙化醇)在调节大鼠钙吸收和骨质量方面比维生素D2(麦角钙化醇)更有效
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-23 DOI: 10.1016/j.jsbmb.2025.106837
Soumam Dutta , Athira Anilkumar Sudharma , Shabna Aboo , Surendar Jatavath , Sivaramakrishna Siginam , Pradeep B. Patil , Sai Santhosh Vadakattu , Mullapudi Venkata Surekha , G. Bhanuprakash Reddy , Ayesha Ismail
{"title":"Vitamin D3 (cholecalciferol) is more efficacious than Vitamin D2 (ergocalciferol) at regulating calcium absorption and bone quality in rats","authors":"Soumam Dutta ,&nbsp;Athira Anilkumar Sudharma ,&nbsp;Shabna Aboo ,&nbsp;Surendar Jatavath ,&nbsp;Sivaramakrishna Siginam ,&nbsp;Pradeep B. Patil ,&nbsp;Sai Santhosh Vadakattu ,&nbsp;Mullapudi Venkata Surekha ,&nbsp;G. Bhanuprakash Reddy ,&nbsp;Ayesha Ismail","doi":"10.1016/j.jsbmb.2025.106837","DOIUrl":"10.1016/j.jsbmb.2025.106837","url":null,"abstract":"<div><div>Differential efficacy of vitamin D2 (D2) versus vitamin D3 (D3) in improving classical functions in target organs remain incompletely understood. Previous studies show contradictory results, with limited comprehensive assessment of functional and molecular outcomes across classical target organs namely intestine, bone and kidney. This study investigated the comparative effects of D2 and D3, administered independently or in combination at different dosages, on these organs using a rat model. Weanling male Sprague-Dawley rats were subjected to a depletion-repletion study design with diets containing D2, D3, combination (D2 +D3), or vitamin D deficient (VDD) diet. Our results demonstrated that vitamin D3 supplementation elevated serum 25(OH)D levels more efficiently compared to vitamin D2, while concurrent D2 administration reduced the potential of D3 to increase 25(OH)D3 levels. Both D2 and D3 maintained serum Ca and PTH in the normal range. Intestinal <sup>45</sup>Ca absorption was higher in groups receiving D3-based diets in a dose-dependent manner. Furthermore, D3 supplementation had superior effects on bone length, width and strength compared to D2. Vitamin D3 more effectively reduced trabecular bone area in the rehabilitation phase. Additionally, the expression of genes involved in renal calcium reabsorption (<em>Trpv5</em>, <em>Calbindin-D28k</em>, <em>Pmca1b</em>) and vitamin D metabolism/function (<em>Cubilin</em>, <em>Vdr</em>) were significantly altered in VDD group and better corrected with D3 than D2 during rehabilitation. These findings suggest that vitamin D3 is more efficacious than vitamin D2 in improving blood levels of 25(OH)D and majority of the classical functions. Hence vitamin D3 appears to be the superior choice for both prevention and rehabilitation purposes.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106837"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phytosterols as modulators of gut-brain axis and neuroinflammation in Alzheimer’s disease: A novel therapeutic avenue in aging research 植物甾醇作为阿尔茨海默病肠脑轴和神经炎症的调节剂:衰老研究的新治疗途径
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106836
Nila Ganamurali , Varsha S B , Sarvesh Sabarathinam
{"title":"Phytosterols as modulators of gut-brain axis and neuroinflammation in Alzheimer’s disease: A novel therapeutic avenue in aging research","authors":"Nila Ganamurali ,&nbsp;Varsha S B ,&nbsp;Sarvesh Sabarathinam","doi":"10.1016/j.jsbmb.2025.106836","DOIUrl":"10.1016/j.jsbmb.2025.106836","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is characterized by amyloid-β deposition and neuroinflammation. Emerging evidence implicates gut microbiota dysbiosis and gut–brain axis dysfunction in AD pathogenesis, while phytosterols—plant sterols similar to cholesterol—modulate microbiota composition, lipid metabolism, and inflammatory pathways. To review evidence of phytosterols as modulators of the gut–brain axis and neuroinflammation in AD, outlining mechanisms, therapeutic potential, and delivery approaches. A literature search of PubMed, Scopus, and Web of Science identified studies on phytosterols, gut microbiota modulation, neuroinflammation, and AD. Mechanistic data on sterol structure–activity relationships, microbiota-derived metabolites, and in vivo AD outcomes were extracted and synthesized. Phytosterols lower systemic cholesterol, cross the blood–brain barrier, and accumulate in neural tissue. They enrich short-chain fatty acid–producing gut microbes, suppress pathogens, and increase secondary bile acids that activate FXR and TGR5 signaling, attenuating neuroinflammation. Preclinical AD models show reduced amyloid-β, decreased microglial activation, and improved cognition. Nanoencapsulation and esterification strategies enhance CNS bioavailability. Phytosterols modulate cholesterol, gut microbiota, and neuroinflammatory pathways through FXR- and TGR5-mediated signaling. Advanced delivery systems and microbiome-informed dosing strategies may enhance their therapeutic precision and uptake. Future studies should focus on stratified human trials to validate efficacy and enable personalized interventions in Alzheimer’s disease.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106836"},"PeriodicalIF":2.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Obituary Étienne-Émile Baulieu (1927-2025). 讣告:Etienne - Emile Baulieu(1927-2025)。
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106834
Jerzy Adamski
{"title":"Obituary Étienne-Émile Baulieu (1927-2025).","authors":"Jerzy Adamski","doi":"10.1016/j.jsbmb.2025.106834","DOIUrl":"10.1016/j.jsbmb.2025.106834","url":null,"abstract":"","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106834"},"PeriodicalIF":2.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Very high-dose vitamin D₃ supplementation reduces the expression of genes and proteins engaged in β-oxidation in healthy pigs 非常高剂量的维生素D₃可以减少健康猪体内参与β-氧化的基因和蛋白质的表达
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-16 DOI: 10.1016/j.jsbmb.2025.106835
Anna Steg , Grzegorz Smołucha , Małgorzata Świątkiewicz , Maria Oczkowicz
{"title":"Very high-dose vitamin D₃ supplementation reduces the expression of genes and proteins engaged in β-oxidation in healthy pigs","authors":"Anna Steg ,&nbsp;Grzegorz Smołucha ,&nbsp;Małgorzata Świątkiewicz ,&nbsp;Maria Oczkowicz","doi":"10.1016/j.jsbmb.2025.106835","DOIUrl":"10.1016/j.jsbmb.2025.106835","url":null,"abstract":"<div><div>Vitamin D plays a multifaceted role in the body, influencing a wide range of physiological processes. While its benefits in deficiency states are well recognized, the effects of high-dose vitamin D₃ supplementation in vitamin D-sufficient individuals remain poorly understood. In this study, we applied an integrative transcriptomic and proteomic approach to assess the dose-dependent effects of long-term dietary vitamin D₃ supplementation (5000 and 10,000 IU/kg feed) in healthy pigs. Despite the absence of phenotypic alterations in fattening characteristics, we observed significant molecular changes in liver tissue, particularly in pathways related to fatty acid β-oxidation, amino acid catabolism, and oxidative stress response. High-dose vitamin D₃ supplementation led to consistent downregulation of key genes and proteins involved in mitochondrial and peroxisomal β-oxidation, including <em>ACSL5</em>, <em>ACADVL</em>, <em>HADHA</em>, <em>ACAA1</em> (gene expression), and ACADM, ECHDC1, and ECHDC2 (protein level). These findings suggest a reduced hepatic capacity for activating and degrading long-, very long-, and medium-chain fatty acids, potentially resulting in the accumulation of lipid intermediates and a shift toward alternative metabolic pathways. Our findings indicate that very high-dose vitamin D₃ supplementation in non-deficient states may lead to adverse metabolic shifts in the liver, including lipid accumulation and compromised energy metabolism. These effects appear to be dose-dependent, and while they may not manifest phenotypically in short-lived species, they offer important insights into non-classical toxicological effects of high-dose vitamin D₃ supplementation. Importantly, this study highlights the context-dependent nature of vitamin D’s effects and provides a new direction for research focused on its metabolic roles beyond classical pathways.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106835"},"PeriodicalIF":2.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of cholesterol homeostasis related genes and potential pathogenesis mechanisms in ulcerative colitis 溃疡性结肠炎胆固醇稳态相关基因的鉴定及其潜在的发病机制
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-09 DOI: 10.1016/j.jsbmb.2025.106833
Jie Wan , Yuchao Zhang , Ning Ge , Hongya Guan , Jia Liu
{"title":"Identification of cholesterol homeostasis related genes and potential pathogenesis mechanisms in ulcerative colitis","authors":"Jie Wan ,&nbsp;Yuchao Zhang ,&nbsp;Ning Ge ,&nbsp;Hongya Guan ,&nbsp;Jia Liu","doi":"10.1016/j.jsbmb.2025.106833","DOIUrl":"10.1016/j.jsbmb.2025.106833","url":null,"abstract":"<div><h3>Background and aims</h3><div>Cholesterol metabolism (CM) plays essential roles in human disease. Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with significant morbidity and healthcare burden. However, the role of CM in UC remains unclear.</div></div><div><h3>Methods</h3><div>Gene expression data of UC patients and control samples were retrieved and merged from GSE75214, GSE92415, GSE16879, and GSE48958. Differential analysis was performed for the identification of cholesterol homeostasis-related differentially expressed genes (DEGs), followed by machine learning for cholesterol homeostasis-related hub DEGs. Five cholesterol homeostasis related genes were identified. We further assessed the related pathways of 5 hub genes.</div></div><div><h3>Results</h3><div>Five overlapped cholesterol homeostasis related genes were identified by DEGs analysis. LIPC, LIPG, CETP, ABCB11, and APOH were identified as hub genes.</div></div><div><h3>Conclusions</h3><div>The current study identified 5 cholesterol homeostasis related genes, LIPC, LIPG, CETP, ABCB11, and APOH, that might play key roles in the development of UC. These findings offer new insights for further exploring UC and its underlying mechanisms.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106833"},"PeriodicalIF":2.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An in-silico investigation of protein–ligand interactions involving dietary flavonoids targeting the nucleotide-binding domain 1 (NBD1) of multidrug resistance-associated protein 1 (MRP1) to overcome multidrug resistance in cancer 一项针对多药耐药相关蛋白1 (MRP1)核苷酸结合结构域1 (NBD1)的膳食黄酮类化合物的蛋白质-配体相互作用的计算机研究,以克服癌症的多药耐药
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-07 DOI: 10.1016/j.jsbmb.2025.106832
Khurshid Ahmad Padder
{"title":"An in-silico investigation of protein–ligand interactions involving dietary flavonoids targeting the nucleotide-binding domain 1 (NBD1) of multidrug resistance-associated protein 1 (MRP1) to overcome multidrug resistance in cancer","authors":"Khurshid Ahmad Padder","doi":"10.1016/j.jsbmb.2025.106832","DOIUrl":"10.1016/j.jsbmb.2025.106832","url":null,"abstract":"<div><div>Multidrug resistance (MDR) continues to pose a tough challenge in the successful chemotherapeutic management of various malignancies. A key contributor to MDR is the multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) transporter family comprising 1531 amino acids. MRP1 actively extrudes a broad spectrum of chemotherapeutic agents from cancer cells, thereby reducing their intracellular accumulation and attenuating their cytotoxic effects. In this study, we performed molecular docking analyses to investigate the binding interactions between a series of naturally occurring dietary flavonoids and the Nucleotide Binding Domain 1 (NBD1) of MRP1, aiming to identify structural determinants that enhance ligand affinity and inform the selection of effective MDR modulators. All docking simulations were conducted using the Glide v5.7 software suite (Schrödinger LLC., Portland, USA) in extra precision mode (GlideXP). The 14 naturally occuring flavonoids assessed, rutin, taxifolin, myricetin, isorhamnetin, apigenin, eriodictyol, chrysin, daidzein and genistein exhibited variable binding affinities toward MRP1-NBD1, with several compounds forming key hydrogen bonds with active site amino acid residues. Notably, rutin demonstrated the highest binding affinity (docking score: –10.1958), forming highly stable hydrogen bonds with SER686 and SER689. Taxifolin and myricetin also showed favorable interactions, primarily involving SER686. These findings highlight the potential of specific dietary flavonoids to serve as functional inhibitors of MRP1-mediated drug efflux. Overall, the structural insights gained underscore the utility of flavonoid based scaffolds as promising candidates for overcoming MDR, thereby improving the therapeutic efficacy of anticancer agents.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106832"},"PeriodicalIF":2.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nano-curcumin attenuates tamoxifen resistance and malignant progression in ER-positive breast cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway 纳米姜黄素通过抑制PI3K/AKT/mTOR信号通路减弱er阳性乳腺癌细胞对他莫昔芬的耐药性和恶性进展。
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-03 DOI: 10.1016/j.jsbmb.2025.106825
Chenguang Zhang, Hu Wang, Hao Lei, Jianghua Ou
{"title":"Nano-curcumin attenuates tamoxifen resistance and malignant progression in ER-positive breast cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway","authors":"Chenguang Zhang,&nbsp;Hu Wang,&nbsp;Hao Lei,&nbsp;Jianghua Ou","doi":"10.1016/j.jsbmb.2025.106825","DOIUrl":"10.1016/j.jsbmb.2025.106825","url":null,"abstract":"<div><div>Breast cancer (BC) is one of the most prevalent malignant tumors among women, with estrogen receptor (ER)-positive patients constituting approximately 70 % of all cases. Endocrine therapy is currently a treatment option for patients with ER-positive BC; however, the development of resistance significantly limits the effectiveness of this treatment. Nano-curcumin (Nano-CUR) possesses anticancer properties and enhances bioavailability by improving the hydrophobic character of curcumin (CUR). However, the underlying mechanism by which Nano-CUR affects tamoxifen (TAM) resistance in ER-positive BC remains unknown. Here, we found that Nano-CUR promoted apoptosis and cell cycle arrest, inhibited cell proliferation and reduced the levels of cancer stem cells (CSCs)-related markers, including octamer-binding protein (OCT4), Nanog homeobox (NANOG) and sex-determining region Y-box 2 (SOX2) in TAM-resistant BC cells. Additionally, Nano-CUR demonstrated the ability to inhibit tumor malignant progression in TAM-treated BC mice. Mechanistically, Nano-CUR blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in MCF-7/TAM and T47D/TAM cells. The activation of this pathway by its activators (PI3K activator 740Y-P, AKT activator SC-79, and mTOR activator MHY1485) effectively alleviated the anti-tumor effect induced by Nano-CUR in TAM-resistant BC cells. Collectively, these findings reveal that Nano-CUR contributes to the reduction of tumorigenesis and TAM resistance in ER-positive BC cells by inhibiting the PI3K/AKT/mTOR signaling pathway.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106825"},"PeriodicalIF":2.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastric mucosal differentially expressed genes after bariatric surgery: Effects on sterol-related pathways 减肥手术后胃粘膜差异表达基因:对固醇相关途径的影响。
IF 2.7 2区 生物学
Journal of Steroid Biochemistry and Molecular Biology Pub Date : 2025-07-01 DOI: 10.1016/j.jsbmb.2025.106824
Maryam Mahjoubin-Tehran , Ali H. Eid , Tannaz Jamialahmadi , Saheem Ahmad , Safia Obaidur Rab , Prashant Kesharwani , Amirhossein Sahebkar
{"title":"Gastric mucosal differentially expressed genes after bariatric surgery: Effects on sterol-related pathways","authors":"Maryam Mahjoubin-Tehran ,&nbsp;Ali H. Eid ,&nbsp;Tannaz Jamialahmadi ,&nbsp;Saheem Ahmad ,&nbsp;Safia Obaidur Rab ,&nbsp;Prashant Kesharwani ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.jsbmb.2025.106824","DOIUrl":"10.1016/j.jsbmb.2025.106824","url":null,"abstract":"<div><div>Obesity is currently recognized as a serious global health problem, which accounts for a considerable morbidity and mortality burden. Bariatric surgery is widely accepted as one of the most effective treatments for severe obesity. Roux-en-Y Gastric Bypass (RYGB) is a common type of bariatric surgery. Although the clinical impact of RYGB has been widely studied, the effects of this intervention at the molecular and genetic levels remain largely unknown. In this study, we aimed to identify differentially expressed genes in gastric mucosa after bariatric surgery <em>vs.</em> before in order to recognize genes and pathways influenced by surgery. Data of GSE76762 was downloaded from GEO (NCBI) database. Gene expression of after surgery samples were compared with before. Genes with a │Log fold change (LFC) │ &gt; 1 and adjusted p-value &lt; 0.05 were defined as differentially expressed genes. It was found that 11 genes were differentially upregulated and 6 genes were differentially downregulated after bariatric surgery. Protein-protein interactions assessed using STRNG online database was significant (p-value: 0.000202). SCD, INSIG1, CYP51A1, and LDLR have strong protein-protein interactions. Gene-gene interaction was investigated using GeneMANIA which showed the high co-expression score (97.78 %). GO and pathway enrichment analysis was investigated using EnrichR. Cholesterol Homeostasis, Sterol Homeostasis, and Cellular Response to Sterol are the best results of biological process. Metabolism of steroids, Steroid regulatory element binding proteins signaling, and Bile secretion are the best results of Reactome, WikiPathway, and KEGG, respectively. Importantly, associations of LDLR, KCNJ13, and PMP22 with Familial hypercholesterolemia, Hyperlipoproteinemia, Charcot-marie-tooth disease type 1 and 4, and Leber congenital amaurosis were discovered.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"254 ","pages":"Article 106824"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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