Molecular and Cellular Biochemistry最新文献

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Canagliflozin improves high-salt-induced aortic arteriosclerosis and premature aging in dahl salt-sensitive rats through the SIRT6/HIF-1 α signaling pathway. 加格列净通过SIRT6/HIF-1 α信号通路改善高盐盐敏感大鼠主动脉硬化和早衰。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-10-01 Epub Date: 2025-06-02 DOI: 10.1007/s11010-025-05321-z
Qiuyan Wang, Yi Liang, Qingjuan Zuo, Lili He, Tingting Zhang, Zhongli Wang, Jianlong Zhai, Boce Cao, Sai Ma, Guorui Zhang, Fan Lu, Kaichuan He, Yan Wang, Yifang Guo
{"title":"Canagliflozin improves high-salt-induced aortic arteriosclerosis and premature aging in dahl salt-sensitive rats through the SIRT6/HIF-1 α signaling pathway.","authors":"Qiuyan Wang, Yi Liang, Qingjuan Zuo, Lili He, Tingting Zhang, Zhongli Wang, Jianlong Zhai, Boce Cao, Sai Ma, Guorui Zhang, Fan Lu, Kaichuan He, Yan Wang, Yifang Guo","doi":"10.1007/s11010-025-05321-z","DOIUrl":"10.1007/s11010-025-05321-z","url":null,"abstract":"<p><p>Hypertension and its complications seriously affect human health, bringing about long-term medical burdens, functional impairments and even death. This study explored the impact of Canagliflozin (CANA) on the blood vessels of salt-sensitive hypertension. Male Dahl salt-sensitive (Dahl SS) rats were fed with an 8% high-salt diet, and then intragastrically given CANA at a dose of 30 mg/kg/day or with a 0.5% hydroxypropyl methylcellulose solution for 12 weeks to induce hypertensive vascular damage and premature aging. Through vascular ultrasound detection, CANA improved the aortic stiffness and hemodynamics of high-salt-fed rats. Through vascular reactivity tests, CANA improved the carotid artery vasodilation. Hematoxylin and eosin (H&E), Sirius red, and senescence associated β-galactosidase staining were performed on the aorta, and CANA improved the fibrosis and aging of the aorta. CANA was found to reduce the expression of senescence associated secretory phenotype in the circulation that was induced by a high-salt diet. Additionally, it increased the expression of Sirtuin 6(SIRT6) in blood vessels and decreased the expression of Hypoxia-inducible factor 1α (HIF-1α) and its target genes. This study has demonstrated for the first time that CANA mitigates salt-induced aortic sclerosis and premature aging via the SIRT6/HIF-1α pathway.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5369-5385"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199620","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
Effects of Lacticaseibacillus rhamnosus LB1.5 as potential probiotic supplement on the liver and adipose tissue of adult male mice to a high-fat diet. 鼠李糖乳杆菌LB1.5作为潜在益生菌补充剂对高脂饮食成年雄性小鼠肝脏和脂肪组织的影响
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-10-01 Epub Date: 2025-06-28 DOI: 10.1007/s11010-025-05344-6
Natália Perin Schmidt, Milena Henrique Ferri, Patrícia Molz, Brenda Santos Fraga, Priscila Dutra Silveira, Daiana Rodrigues Dos Santos, Juan Andres Cuadro Montanez, Gabriela Merker Breyer, Amanda de Souza da Motta, Marilene Porawski, Alethea Gatto Barschak, Renata Padilha Guedes, Márcia Giovenardi
{"title":"Effects of Lacticaseibacillus rhamnosus LB1.5 as potential probiotic supplement on the liver and adipose tissue of adult male mice to a high-fat diet.","authors":"Natália Perin Schmidt, Milena Henrique Ferri, Patrícia Molz, Brenda Santos Fraga, Priscila Dutra Silveira, Daiana Rodrigues Dos Santos, Juan Andres Cuadro Montanez, Gabriela Merker Breyer, Amanda de Souza da Motta, Marilene Porawski, Alethea Gatto Barschak, Renata Padilha Guedes, Márcia Giovenardi","doi":"10.1007/s11010-025-05344-6","DOIUrl":"10.1007/s11010-025-05344-6","url":null,"abstract":"<p><p>This study aimed to investigate the effects of Lacticaseibacillus rhamnosus LB1.5 supplementation on liver and adipose tissue morphology, oxidative stress, and the relative gene expression of Sirt1, Gpx1, and Il6 in the liver of HFD-fed mice. Male C57BL/6 mice received: (i) a control diet (CONT), (ii) a control diet with probiotics (Lact. rhamnosus LB1.5, 1.3 × 10⁸ CFU/mL, three times a week; CONT + PROB), (iii) a high-fat diet (HFD), or (iv) a high-fat diet with probiotics (HFD + PROB) for 13 weeks. The HFD group showed significant liver alterations, including lipid accumulation, severe steatosis, hepatocellular ballooning, and an increase in Il6 relative gene expression, as well as an interaction effect on Sirt1 relative gene expression (p < 0.05). Nevertheless, these changes were not mitigated by probiotic supplementation (p > 0.05). Additionally, HFD-fed mice exhibited significant alterations in adipose tissue (p < 0.05), such as increased tissue weight, a lower number of adipocytes per area, and larger adipocyte size per area, with no significant effect of the probiotic observed (p > 0.05). In the liver, high TBARS levels were found in the HFD group, and a probiotic supplementation effect on sulfhydryl levels was observed only in the HFD + PROB group (p < 0.05). Unlike, in adipose tissue, redox status was not affected by diet or supplementation (p > 0.05). In conclusion, our results demonstrated the pro-inflammatory effects of an obesogenic diet and suggest that Lact. rhamnosus LB1.5 supplementation contributes only to the enhancement of liver redox status, improving antioxidant defenses by increasing sulfhydryl levels.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5531-5543"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528916","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
The role of lncRNA-ZFAS1 in liver fibrosis: insights into the miR-1953/TAZ axis. lncRNA-ZFAS1在肝纤维化中的作用:miR-1953/TAZ轴的见解。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-10-01 Epub Date: 2025-06-17 DOI: 10.1007/s11010-025-05335-7
Binbo Fang, Weizhi Zhang, Mengyuan Li, Jianjian Zheng, Hui Jin
{"title":"The role of lncRNA-ZFAS1 in liver fibrosis: insights into the miR-1953/TAZ axis.","authors":"Binbo Fang, Weizhi Zhang, Mengyuan Li, Jianjian Zheng, Hui Jin","doi":"10.1007/s11010-025-05335-7","DOIUrl":"10.1007/s11010-025-05335-7","url":null,"abstract":"<p><p>Long non-coding RNA-Zinc finger antisense 1 (lncRNA-ZFAS1) is involved in the progression of several cancer types, yet its function in liver fibrosis remains unclear. The purpose of this study was to examine ZFAS1 expression in liver fibrosis and explore its possible molecular mechanism. ZFAS1 expression was measured in a liver fibrosis model and in activated hepatic stellate cells (HSCs). The impact of ZFAS1 silencing on HSC growth, collagen production, and epithelial-mesenchymal transition (EMT) was assessed. The connection between ZFAS1 and miR-1953 was investigated using bioinformatics analysis and luciferase reporter gene experiments. Moreover, in vivo studies were performed to confirm the effect of ZFAS1 knockdown on liver fibrosis progression. ZFAS1 was significantly upregulated in the liver fibrosis model and activated HSCs. Silencing ZFAS1 helped to inhibit the growth and activation of HSCs, along with reduced levels of type I collagen and α-SMA. In vivo experiments confirmed that ZFAS1 knockdown alleviated the progression of fibrosis and collagen deposition. Mechanistic studies revealed that ZFAS1 promoted HSC EMT through the regulation of the miR-1953/TAZ axis, thereby exerting a pro-fibrotic effect. By influencing the miR-1953/TAZ signaling pathway, ZFAS1 significantly contributes to the activation and EMT of HSCs in liver fibrosis development. These findings highlight ZFAS1 as a potential therapeutic target for treating liver fibrosis, offering new avenues for clinical intervention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5473-5484"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317479","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
Treatment with crocin attenuates cardiac metabolic disturbances and subsequent inflammation in streptozotocin-induced diabetes. 用藏红花素治疗可减轻链脲佐菌素引起的糖尿病的心脏代谢紊乱和随后的炎症。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-10-01 Epub Date: 2025-06-03 DOI: 10.1007/s11010-025-05320-0
Dimitra Palioura, Konstantinos Feidantsis, Antigone Lazou
{"title":"Treatment with crocin attenuates cardiac metabolic disturbances and subsequent inflammation in streptozotocin-induced diabetes.","authors":"Dimitra Palioura, Konstantinos Feidantsis, Antigone Lazou","doi":"10.1007/s11010-025-05320-0","DOIUrl":"10.1007/s11010-025-05320-0","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a metabolic disorder closely associated with cardiac dysfunction. Natural products are considered potential candidates for the management of DM. Crocin, a natural carotenoid derived from saffron, has been reported to possess several pharmacological properties, including cardioprotective effects. The aim of the present study was to investigate the beneficial effects of crocin on the metabolic derangement of the diabetic myocardium. Streptozotocin (STZ)-induced diabetic rats were treated with 10 mg/kg of crocin daily for two weeks. Oral administration of crocin normalized blood glucose, HbA1c, triglycerides, total cholesterol, LDL, and HDL levels. Notably, crocin reduced the elevated protein levels of cardiac PPARα and PPARδ-major transcriptional regulators of cardiac metabolism-back to normal. Consequently, the expression of the fatty acid (FA) transporter CD36 was downregulated, the activity of the FA oxidation enzyme 3-hydroxyacyl-CoA dehydrogenase (HOAD) was decreased, and intramyocardial triglyceride accumulation returned to physiological levels. Furthermore, crocin improved glucose uptake and metabolism in the diabetic myocardium, as evidenced by increased Akt phosphorylation, translocation of GLUT4 to the plasma membrane, enhanced activity of pyruvate kinase, and downregulation of pyruvate dehydrogenase kinase 4 (PDK4). Importantly, the stimulatory effect of crocin on Akt phosphorylation was also confirmed in isolated cardiac myocytes exposed to high glucose, further supporting its direct role in modulating glucose signaling pathways. Crocin treatment also reduced STZ-induced elevations in the levels of inflammatory cytokines-interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)-as well as the phosphorylation of IκBα, bringing them close to basal levels. Overall, these findings suggest that crocin activates Akt signaling and thereby alleviates diabetes-induced metabolic disturbances by restoring the balance between glucose and fatty acid utilization in the hearts of STZ-induced diabetic rats. Therefore, crocin supplementation may represent a promising approach for the development of natural compound-based adjunct therapies for diabetic cardiomyopathy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5387-5397"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216346","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
Interconnection between gut microbial metabolites and mitochondrial ROS production: implications for cellular health. 肠道微生物代谢物和线粒体活性氧产生之间的相互联系:对细胞健康的影响。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-30 DOI: 10.1007/s11010-025-05397-7
Priyanka Gupta, Sumit Dutta, Krishanu Dutta, Piyush Bhattacharjee, Arjama Hazra, Rajiv Jash
{"title":"Interconnection between gut microbial metabolites and mitochondrial ROS production: implications for cellular health.","authors":"Priyanka Gupta, Sumit Dutta, Krishanu Dutta, Piyush Bhattacharjee, Arjama Hazra, Rajiv Jash","doi":"10.1007/s11010-025-05397-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05397-7","url":null,"abstract":"<p><p>Trillions of microbes inhabit the human gut and engage in diverse biological processes by secreting different metabolites. These metabolites influence mitochondrial function and produce ROS. This gut-mitochondrial communication plays a pivotal role in regulating cellular homeostasis, energy production, and oxidative stress management, all required for optimal health. Short-chain fatty acids, secondary bile acids, amines, and gaseous metabolites are major gut metabolites that aid in governing mitochondrial processes to facilitate effective energy production and avoid oxidative damage. In the case of damaged mitochondrial function, it can alter gut flora (dysbiosis), resulting in inflammation and assisting a number of diseases such as multiple sclerosis, Alzheimer's disease, IgA nephropathy, inflammatory bowel disease, and colorectal cancer. The gut-mitochondria axis is a multifaceted interaction that regulates a cell's energy homeostasis and provides novel therapeutic opportunities. Probiotics, prebiotics, dietary modifications, and metabolite therapies have the potential to restore gut-microbe balance, enhance mitochondrial function, and reduce oxidative stress. These measures have the potential for new treatments for many diseases by modulating the gut-mitochondria axis. This review surveys interactions among gut microbiota, mitochondrial ROS, and the gut-mitochondria axis, describing how such relationships affect health and disease.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200374","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
Metabolomics of abdominal adipose tissue samples collected from patients with obesity - a critical review. 从肥胖患者收集的腹部脂肪组织样本的代谢组学——一项重要的综述。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-29 DOI: 10.1007/s11010-025-05399-5
Alina Jaroch
{"title":"Metabolomics of abdominal adipose tissue samples collected from patients with obesity - a critical review.","authors":"Alina Jaroch","doi":"10.1007/s11010-025-05399-5","DOIUrl":"https://doi.org/10.1007/s11010-025-05399-5","url":null,"abstract":"<p><p>Obesity is a multifactorial metabolic disorder characterized by excessive fat accumulation and associated with numerous health risks, including insulin resistance, cardiovascular disease, and metabolic syndrome. Adipose tissue, particularly subcutaneous (SAT) and visceral (VAT) fat, plays a central role in metabolic regulation, yet its biochemical properties and functions differ significantly. While metabolomics offers a promising approach to studying adipose tissue at a molecular level, significant methodological limitations and inconsistencies in study design undermine the reliability of current findings. Although VAT is frequently characterized by a pro-inflammatory and lipolytic metabolic profile, whereas SAT is more involved in lipid storage and insulin, these generalizations overlook important depot-specific variations and fail to address the heterogeneity within adipose tissue. This critical review evaluates existing metabolomic studies, identifying key discrepancies in lipid metabolism, energy homeostasis, and inflammation-related pathways across VAT and SAT. It highlights the need for improved standardization in metabolomic analyses, greater inclusion of diverse populations, and more robust longitudinal studies. By addressing these issues, future research can provide more precise insights into adipose tissue's role in obesity-related metabolic dysfunction and better inform clinical strategies for obesity management.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192146","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
Monoamine oxidases are mediators of oxidative stress in human varicose Veins: interactions with obesity, inflammation, and angiotensin II. 单胺氧化酶是人类静脉曲张氧化应激的介质:与肥胖、炎症和血管紧张素II的相互作用。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-29 DOI: 10.1007/s11010-025-05398-6
Sonia Raţiu, Adrian Sturza, Paul S Muntean, Claudia Borza, Tiberiu Bratu, Danina M Muntean
{"title":"Monoamine oxidases are mediators of oxidative stress in human varicose Veins: interactions with obesity, inflammation, and angiotensin II.","authors":"Sonia Raţiu, Adrian Sturza, Paul S Muntean, Claudia Borza, Tiberiu Bratu, Danina M Muntean","doi":"10.1007/s11010-025-05398-6","DOIUrl":"https://doi.org/10.1007/s11010-025-05398-6","url":null,"abstract":"<p><p>Chronic venous disease (CVD) and its clinical manifestation, the varicose veins (VVs), are characterized by progressive structural and functional alterations of the venous walls, with obesity/overweight being one of the most frequent comorbidities. Monoamine oxidases (MAO-A and MAO-B) are mitochondrial flavoenzymes responsible for the constant generation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) during the catabolism of biogenic monoamines and neurotransmitters that contribute, when upregulated, to the oxidative stress in most mammalian tissues. However, their role in the VV pathophysiology and its modulation by vasoactive stimuli such as angiotensin II (Ang II) remains unclear. This exploratory study was double-aimed i) to assess MAO expression in human VV samples in relation to obesity and systemic inflammation and ii) to determine the impact of pharmacological MAO inhibition on oxidative stress under basal and Ang II-stimulated conditions. To this aim, 20 patients with VV and an indication for cryostripping were randomized according to their body mass index (BMI) into obese (n = 10) and non-obese (n = 10) groups, and VV samples were harvested and used to assess the following: i) MAO-A and MAO-B gene expression by qRT-PCR, as well as expression and localization by immunofluorescence, and ii) H<sub>2</sub>O<sub>2</sub> by means of the ferrous xylenol orange oxidation (FOX) assay. Furthermore, the effect of selective MAO inhibition (clorgyline 10 μM for MAO-A, selegiline 10 μM for MAO-B) was tested ex vivo both at baseline and following acute stimulation with Ang II (100 nM). We showed that both MAO-A and MAO-B are constitutively expressed in the human venous walls, with higher levels in the varicose veins than in the adjacent perforator veins. The obese patients with inflammatory status (elevated serum C-reactive protein) had significantly increased MAO-A (but not MAO-B) expression as compared to the non-obese controls (p < 0.01). Acute ex vivo incubation with Ang II further enhanced the expression of both isoforms and increased H<sub>2</sub>O<sub>2</sub> generation. MAO inhibition significantly mitigated the oxidative stress in both non-stimulated and Ang II-stimulated samples, regardless of the presence or absence of obesity. In conclusion, MAO isoforms, in particular MAO-A, are upregulated in the human varicose veins and can be further induced by Ang II, especially in the setting of obesity associated with low-grade inflammation. MAO contributed to the local oxidative stress, which was significantly reduced by its pharmacological inhibition with MAO-A and B inhibitors, thus pointing to MAO as a potential therapeutic target in patients with CVD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186373","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
FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation. FKH结构域介导的核FOXP3通过c-MYC/CDKN1A调控、EMT抑制和PI3K/AKT信号调节抑制胃癌恶性肿瘤。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-24 DOI: 10.1007/s11010-025-05387-9
Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie
{"title":"FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation.","authors":"Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie","doi":"10.1007/s11010-025-05387-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05387-9","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137999","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
Downregulation of Tra2α and Tra2β suppresses lipopolysaccharide-induced inflammation in macrophages by regulating MyD88 mRNA alternative splicing. 下调Tra2α和Tra2β通过调节MyD88 mRNA选择性剪接抑制巨噬细胞脂多糖诱导的炎症。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-23 DOI: 10.1007/s11010-025-05394-w
Yu Fu, Luyao Zhang, Yanjing Wang, Bo Cheng, Weiye Shi, Peiyuan Chen, Jinyu Liu, Xiaolei Zhou, Yingze Wang
{"title":"Downregulation of Tra2α and Tra2β suppresses lipopolysaccharide-induced inflammation in macrophages by regulating MyD88 mRNA alternative splicing.","authors":"Yu Fu, Luyao Zhang, Yanjing Wang, Bo Cheng, Weiye Shi, Peiyuan Chen, Jinyu Liu, Xiaolei Zhou, Yingze Wang","doi":"10.1007/s11010-025-05394-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05394-w","url":null,"abstract":"<p><p>RNA binding proteins (RBPs) play a pivotal role in the posttranscriptional regulation of inflammatory processes. Transformer-2 (Tra2) is an evolutionarily conserved RBP that regulates mRNA alternative splicing, encoding two homologous proteins in vertebrates, Tra2α and Tra2β. Dysregulation of Tra2α or Tra2β may lead to the development of several inflammatory diseases. However, the roles of Tra2α and Tra2β in inflammation remain unclear. In the current research, the expression levels of Tra2α and Tra2β were upregulated in RAW264.7 macrophage cells stimulated by lipopolysaccharide (LPS). Downregulation of Tra2α or Tra2β inhibited the expression of inflammatory factors induced by LPS. Notably, combined suppression of Tra2α and Tra2β cooperatively reduced LPS-activated inflammation and suppressed the activation of NFκB and MAPK pathways. Myeloid differentiation primary response gene 88 (MyD88), a crucial adaptor in the TLR4 pathway, expresses splicing variants MyD88-L and MyD88-S, which exert pro-inflammatory and anti-inflammatory effects, respectively. We found that Tra2α and Tra2β proteins interacted with MyD88 mRNA. Moreover, downregulation of Tra2α and Tra2β promoted the expression of MyD88-S mRNA variants, thereby modulating the inflammatory response. Therefore, our findings demonstrated that Tra2α and Tra2β cooperatively regulated inflammation by modulating the alternative splicing of MyD88 in LPS-stimulated macrophages. These mechanistic insights into Tra2-mediated regulation of macrophage inflammation may provide novel therapeutic targets for treating inflammatory diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124804","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
Mitochondrial abnormalities in nondiabetic and nonhypertensive glomerular diseases: a comprehensive review. 线粒体异常在非糖尿病和非高血压肾小球疾病:一个全面的回顾。
IF 3.7 2区 生物学
Molecular and Cellular Biochemistry Pub Date : 2025-09-23 DOI: 10.1007/s11010-025-05393-x
Baris Afsar, Rengin Elsurer, Krista L Lentine
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