Zulema Rodriguez-Hernandez, Anabel Paredes-Douton, Marta Galvez-Fernandez, Maria Grau-Perez, Mercedes Sotos-Prieto, Pilar Rentero-Garrido, Montserrat Gonzalez-Estecha, Maria Teresa Llorente-Ballesteros, Jose L Gomez-Ariza, Belen Callejon-Leblic, Pablo Fernandez-Navarro, Martin Laclaustra, Ana Cenarro, Fernando Civeira, Ronald A Glabonjat, Daniel Monleon, Roberto Pastor-Barriuso, Belen Moreno-Franco, Tamara Garcia-Barrera, Maria Tellez-Plaza
{"title":"Non-genetic and genetic determinants of serum selenium and selenium species in the Aragon Workers Health Study.","authors":"Zulema Rodriguez-Hernandez, Anabel Paredes-Douton, Marta Galvez-Fernandez, Maria Grau-Perez, Mercedes Sotos-Prieto, Pilar Rentero-Garrido, Montserrat Gonzalez-Estecha, Maria Teresa Llorente-Ballesteros, Jose L Gomez-Ariza, Belen Callejon-Leblic, Pablo Fernandez-Navarro, Martin Laclaustra, Ana Cenarro, Fernando Civeira, Ronald A Glabonjat, Daniel Monleon, Roberto Pastor-Barriuso, Belen Moreno-Franco, Tamara Garcia-Barrera, Maria Tellez-Plaza","doi":"10.1016/j.freeradbiomed.2025.03.044","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2025.03.044","url":null,"abstract":"<p><p>Understanding potential determinants of selenium biomarkers can help to unravel selenium health effects. We evaluated the contribution of non-genetic (sociodemographic and lifestyle) and genetic factors to serum selenium biomarkers and selenium species (quantified as selenium) including selenium in glutathione peroxidase (GPx), selenoprotein P (SeP), selenoalbumin (SeAlb) and total selenometabolites (Se-metabolites) in the Aragon Workers Health Study (AWHS), a predominantly male cohort of car assembly factory workers in Spain. Total serum selenium and selenium species were measured by HPLC/ICP-QQQ-MS in 1,624 AWHS participants. Blood and urine selenium, measured by ICP-MS, were available in a subset. A Healthy Lifestyle Score (HLS) included Mediterranean diet, physical activity, smoking, BMI and alcohol intake. Candidate gene and genome-wide discovery analyses (CGA and GDA, respectively) were based on TOPMed imputed SNPs. In sex and age-adjusted models, overall HLS, physical activity, and specific foods intake showed positive associations with serum total selenium, SeAlb and Se-metabolites concentrations. The associations between smoking status and BMI with total serum selenium; age, smoking status, BMI and meat intake with SeAlb; and smoking status with Se-metabolites, were inverse. In the GDA, we identified 20, 24, 21, 26, 16, 20 and 68 independent genetic loci for serum total selenium, GPx, SeP, SeAlb, Se-metabolites, and total blood and urine selenium, respectively, with some overlapping genes also relevant in the CGA. Enrichment analysis pointed to biological pathways including circadian rhythm regulation, immune system processes, signaling and receptor- and transporter-related pathways. The explained variability of selenium markers ranged from 15 % for SeP to 21 % for SeAlb and from 0.2 % for SeP to 3.5% for SeAlb in environmental determinants-adjusted models with and without the specific selenium biomarker polygenic score, respectively. While the genetic contribution is substantial, selenium status might be influenced by reinforced healthy lifestyle interventions. Follow-up genetic studies to evaluate selenium health consequences are granted.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751959","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}
Klara Coello , Sharleny Stanislaus , Julie Lyng Forman , Hanne Lie Kjærstad , Kimie Stefanie Ormstrup Sletved , Kamilla Woznica Miskowiak , Maria Faurholt-Jepsen , Klaus Munkholm , Henrik Enghusen Poulsen , Maj Vinberg , Jens Lykkesfeldt , Lars V. Kessing
{"title":"Investigation of malondialdehyde as a trait marker associated with familial risk in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives – A longitudinal cohort study","authors":"Klara Coello , Sharleny Stanislaus , Julie Lyng Forman , Hanne Lie Kjærstad , Kimie Stefanie Ormstrup Sletved , Kamilla Woznica Miskowiak , Maria Faurholt-Jepsen , Klaus Munkholm , Henrik Enghusen Poulsen , Maj Vinberg , Jens Lykkesfeldt , Lars V. Kessing","doi":"10.1016/j.freeradbiomed.2025.03.041","DOIUrl":"10.1016/j.freeradbiomed.2025.03.041","url":null,"abstract":"<div><h3>Aims</h3><div>Increased oxidative stress-generated tissue damage seems to play a pivotal role in the pathophysiology and progression of bipolar disorder (BD). Malondialdehyde (MDA), a product of lipid oxidation, may represent a trait marker in BD associated with familial risk. However, MDA is scarcely studied in patients with <em>newly diagnosed</em> bipolar disorder (BD) and their unaffected relatives (UR).</div></div><div><h3>Methods</h3><div>In this prospective \"the Bipolar Illness Onset study\", we investigated repeated measurements of MDA in a cohort of 371 patients with newly diagnosed/first-episode BD (1016 visits), 139 of their unaffected first-degree relatives (307 visits) and 199 healthy control individuals (HC) with no personal or first-degree family history of affective disorder (537 visits) with a median follow-up time of 2.0. [0.1; 3.8] years for patients with BD, 1.4 [0; 2.4] years for UR, and 2.5 [1.1; 3.9] years for HC. Amongst patients with BD, we further investigated associations of MDA with affective phases and medicine- and illness variables over a period of 7 years.</div></div><div><h3>Results</h3><div>Unaffected relatives had 42.3 % higher levels of MDA at baseline compared with HC in analyses adjusted for sex and age corrected for multiple comparisons (<em>B</em> = = 1.423, 95 % CI = 1.139, 1.777, p = <0.044). However, this difference did not persist over time. No statistically significant differences in MDA levels were observed over time between BD patients and either HC or UR. Additionally, MDA levels were not associated with psychotropic use, illness variables, or affective phase alterations.</div></div><div><h3>Conclusions</h3><div>Against expectations, our findings did not support increased lipid oxidation being a trait phenomenon in BD.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"233 ","pages":"Pages 186-195"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751958","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}
{"title":"Paeoniflorin alleviated experimental Sjögren's syndrome by inhibiting NLRP3 inflammasome activation of submandibular gland cells via activating Nrf2/HO-1 pathway.","authors":"Tingting Jiang, Xuanqi Liu, Shumin Wang, Yu Chen, Yong Wang, Xiaojing Li, Genhong Yao","doi":"10.1016/j.freeradbiomed.2025.03.043","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2025.03.043","url":null,"abstract":"<p><strong>Background: </strong>Total glucosides of white paeony (TGP) has been used for treatment of Sjögren's syndrome (SS) patients. Paeoniflorin (PF) is the main active ingredient of TGP and has antioxidant and anti-inflammatory effects, but its underlying mechanism on SS remains to be explored. Aberrant activation of NLRP3 inflammasome can cause injury of submandibular gland (SG) in SS. However, whether PF regulates NLRP3 inflammasome activation in SS is unknown.</p><p><strong>Objective: </strong>This study aims to investigate whether PF alleviated SS through suppressing NLRP3 inflammation activation. To explore the mechanism of PF in improving Sjögren-like symptoms in non-obese diabetic (NOD) mice.</p><p><strong>Methods: </strong>The gene expression profiles of the labial gland (LG) between SS patients and non-SS patients were analyzed by bioinformatics. Non-obese diabetic (NOD) mice were selected as SS model. Mice were divided into normal saline group and two different doses of PF-treatment groups (50 and 100 mg/kg). The SS-like symptoms and pathological changes of submandibular gland (SG) were analyzed after 4 weeks of administration. SG cells were treated with or without PF and with or without ML385 (a specific inhibitor of Nrf2) in vitro, and then lipopolysaccharide(LPS) and adenosine triphosphate (ATP) were used to induce NLRP3 inflammasome activation in SG cells. Results NLRP3 was up-regulated in LG of SS patients and SG of SS mice. PF alleviated SS-like symptoms in SS mice Compared with control group, NLRP3 and caspase-1 in the SG, and serum IL-1β and IL-18 of NOD mice were decreased in PF group. Furthermore, we found that PF inhibited NLRP3 activation via activating the Nrf2/HO-1 pathway in SG cells. In addition, we observed the activation of Nrf2/HO-1 in the SG of mice after PF administration.</p><p><strong>Conclusions: </strong>Our findings suggested that PF inhibited NLRP3 inflammasome activation through regulating the Nrf2/HO-1 axis in SG of SS mice, which might be the underlying mechanism for the therapeutic effects of PF on SS.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751960","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}
Hong-Ying Li , Jingfan Wang , Tianhao Xiao , Qinyuan Gu , Yuanyuan Fan , Pengfei Ge , Jingyi Xu , Cheng Wang , Ping Xie , Zizhong Hu
{"title":"STING immune activation of microglia aggravating neurovascular unit damage in diabetic retinopathy","authors":"Hong-Ying Li , Jingfan Wang , Tianhao Xiao , Qinyuan Gu , Yuanyuan Fan , Pengfei Ge , Jingyi Xu , Cheng Wang , Ping Xie , Zizhong Hu","doi":"10.1016/j.freeradbiomed.2025.03.042","DOIUrl":"10.1016/j.freeradbiomed.2025.03.042","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is the leading cause of blindness and is pathologically characterized by neuroinflammation and neovascularization. Retinal homeostasis is critically maintained by the retinal neurovascular unit (NVU), which can be disrupted by abnormal activation of microglia in DR. However, the underlying mechanism remains unclear. Here, we provide the first evidence of upregulated stimulator of interferon genes (STING) in microglia within fibrovascular membranes (FVMs) and retinas from oxygen-induced retinopathy (OIR) and streptozotocin (STZ)-induced diabetic mice. Furthermore, we identified STING upregulation in BV2 cells stimulated with high glucose (HG) or hypoxia, accompanied by mitochondrial dysfunction and cytoplasmic leakage of damaged mitochondrial DNA (mtDNA). Pharmacologic or genetic inhibition of STING in microglia prevented their activation and polarization. Next, we demonstrated that STING-deficient BV2 cells reversed the proangiogenic behavior of endothelial cells and protected retinal ganglion cells (RGCs) from oxidative stress. Finally, intravitreal injection of AAV-STING alleviated retinal neurovascular pathologies in both OIR and STZ mice. This study demonstrated that the release of mtDNA mediates STING immune activation of microglia, which further exacerbates NVU damage in DR. In contrast, immunosuppressing STING in microglia could serve as a potential therapeutic strategy.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"233 ","pages":"Pages 86-101"},"PeriodicalIF":7.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725675","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}
Frederick Hartung, Jean Krutmann, Thomas Haarmann-Stemmann
{"title":"Evidence that the aryl hydrocarbon receptor orchestrates oxinflammatory responses and contributes to airborne particulate matter-induced skin aging.","authors":"Frederick Hartung, Jean Krutmann, Thomas Haarmann-Stemmann","doi":"10.1016/j.freeradbiomed.2025.03.040","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2025.03.040","url":null,"abstract":"<p><p>Exposure to airborne particulate matter (PM) is a substantial threat to public health, contributing to respiratory, cardiovascular, and skin-related diseases. Population-based studies strongly indicate that chronic exposure to airborne PM, especially combustion-derived PM<sub>2.5</sub>, accelerates skin aging and thus reduces the quality of life of those affected. There is increasing evidence that especially PM-bound polycyclic aromatic hydrocarbons (PAHs) critically contribute to the clinical manifestation of skin aging, i.e. the development of lentigines/pigment spots and coarse wrinkles. PAHs harm human skin primarily by activating the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor amongst others involved in orchestrating xenobiotic metabolism and immune responses. In this review, we summarize the available population-based data linking particulate air pollution exposure to skin aging. We explain in detail how PAH-rich PM induces the formation of oxidative stress, the release of pro-inflammatory mediators, the expression extracellular matrix degrading metalloproteases, and melanin synthesis, in an AHR-dependent manner, and how these events may culminate in the development of pigment spots and wrinkles, respectively. We also review the current data on the interaction of airborne PM with another factor of the skin aging exposome that exerts its deleterious effects in part through AHR-dependent signaling pathways, namely solar ultraviolet radiation.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742747","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}
Yu Han , Yuhui Zhang , Jianjun Chen , Shouchuan Jiang , Yi Zheng , Yecheng Xu , Yunqin Li , Jingxia Kong , Xin Yu , Huahua Du
{"title":"Iron overload exacerbates metabolic dysfunction-associated steatohepatitis via the microbiota-gut-liver axis through lipopolysaccharide-mediated Akr1b8 activation","authors":"Yu Han , Yuhui Zhang , Jianjun Chen , Shouchuan Jiang , Yi Zheng , Yecheng Xu , Yunqin Li , Jingxia Kong , Xin Yu , Huahua Du","doi":"10.1016/j.freeradbiomed.2025.03.039","DOIUrl":"10.1016/j.freeradbiomed.2025.03.039","url":null,"abstract":"<div><div>Iron homeostatic is closely linked to the development of metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanisms remain poorly understood. HFE knockout (KO) mice were used to generate mild iron-overload models. MASH was induced by feeding mice a methionine- and choline-deficient (MCD) diet for 4 weeks. Iron overload significantly exacerbated the pathologies of MCD-induced MASH, including liver injury, hepatic lipid accumulation, inflammation, and fibrosis. Additionally, iron overload reshaped the composition of gut microbiota, and fecal microbiota transplantation assay proved that gut microbiota from iron-overload mice contributed to hepatic lipid accumulation in control mice. Furthermore, iron overload-induced dysbacteriosis altered the metabolite profiles, reducing short-chain fatty acid levels and increasing lipopolysaccharide (LPS) levels. Notably, elevated LPS levels upregulated the expression of aldo-keto reductase family 1 member B8 (Akr1b8), which accelerated lipid accumulation and inflammation in hepatocytes. Above results indicated that iron overload promoted MASH progression through the microbiota-gut-liver axis, mediated by LPS-induced activation of Akr1b8. These findings highlight the critical role of iron homeostasis and gut microbiota in MASH pathogenesis.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"233 ","pages":"Pages 196-208"},"PeriodicalIF":7.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742751","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}
Kevin R Rarick, Keguo Li, Ru-Jeng Teng, Xigang Jing, Dustin P Martin, Hao Xu, Deron W Jones, Neil Hogg, Cheryl A Hillery, Guilherme Garcia, Billy W Day, Stephen Naylor, Kirkwood A Pritchard
{"title":"Corrigendum to 'Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease' [Free Radic. Biol. Med. 215 (2024) 112-126].","authors":"Kevin R Rarick, Keguo Li, Ru-Jeng Teng, Xigang Jing, Dustin P Martin, Hao Xu, Deron W Jones, Neil Hogg, Cheryl A Hillery, Guilherme Garcia, Billy W Day, Stephen Naylor, Kirkwood A Pritchard","doi":"10.1016/j.freeradbiomed.2025.03.028","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2025.03.028","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729663","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}
Meinhard Wlaschek, Pallab Maity, Albert Kallon Koroma, Hartmut Geiger, Karmveer Singh, Karin Scharffetter-Kochanek
{"title":"Imbalanced Redox Dynamics Induce Fibroblast Senescence Leading to Impaired Stem Cell Pools and Skin Aging.","authors":"Meinhard Wlaschek, Pallab Maity, Albert Kallon Koroma, Hartmut Geiger, Karmveer Singh, Karin Scharffetter-Kochanek","doi":"10.1016/j.freeradbiomed.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2025.03.024","url":null,"abstract":"<p><p>Skin function depends on a meticulously regulated dynamic interaction of distinct skin compartments such as the epidermis and dermis. Adaptive responses at the molecular and cellular level are essential for these interactions - and if dysregulated - drives skin aging and other pathologies. After defining the role of redox homeodynamics in physiology and aging pathology, we focus on the redox distress-dependent aging of dermal fibroblasts including their progenitors. We here discuss the prime role of senescent fibroblasts in the control of their own endogenous niche and stem cell niches for epidermal stem cells, hair follicle stem cells, adipocyte precursors and muscle stem cells. We here review that redox imbalance induced reduction in Insulin-like Growth Factor-1 drives skin aging by the depletion of stem cell pools. This reduction is mediated via the redox-sensitive transcription factor JunB and also by the redox-dependent changes in sphingolipid-metabolism, among others. In addition, we will discuss the changes in the extracellular matrix of the skin affecting cellular senescence and the skin integrity and function in aging. The aim is a deeper understanding of the two main redox-dependent hubs such as JunB-induced depletion of IGF-1, and the sphingolipid-mediated remodeling of the cell membrane with its impact on IGF-1, fibroblast heterogeneity, function, senescence and plasticity in skin aging.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742749","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}
Keshava Prasad , Sunil C. Kaul , Renu Wadhwa , Kanive P. Guruprasad , Kapaettu Satyamoorthy
{"title":"Cellular oxidative stress and sirtuins mediate regulation of senescence and neuronal differentiation by withaferin A","authors":"Keshava Prasad , Sunil C. Kaul , Renu Wadhwa , Kanive P. Guruprasad , Kapaettu Satyamoorthy","doi":"10.1016/j.freeradbiomed.2025.03.038","DOIUrl":"10.1016/j.freeradbiomed.2025.03.038","url":null,"abstract":"<div><div>Withaferin A (WA) and Withanone (WN), the steroidal lactones are pharmacologically established for anticancer and chemopreventive effects in certain cancers. However, their effects on redox modulations, mechanisms stimulating senescence and neuronal differentiation in neuroblastoma cells are less understood. Here we examined the influence of WA on perturbations in the molecular architecture of growth, differentiation and senescence of human brain cancer cell SH SY5Y <em>in vitro</em> and test its efficacy in mouse tumor models. We found senescence induction amplified by WA as determined by a senescence-associated β-galactosidase assay. This led us to evaluate DNA damage which was enhanced as measured by phospho-γH2AX foci formation, directed by reactive oxygen species (ROS) production as determined by flow cytometry and confocal imaging. Furthermore, we assessed the influence of DNA damage on cell cycle arrest and DNA repair. Neurosphere formation assay was performed to demonstrate the stem cell inhibitory potential of WA. Subcutaneous xenograft of neuroblastoma cells in athymic Balb/c mice was performed followed by treatment with WA and tumor growth inhibition was established. <em>Withania somnifera</em> (WS) extract and WA induced alterations in ROS, triggering DNA damage and concomitantly regulated SIRTs expression leading to activation of senescence in SH SY5Y cells. Upon prolonged incubation, differentiation into neuronal lineages was confirmed by using differentiation markers such as neurofilament medium, nestin, MAP2 and synaptophysin as measured by immunofluorescence and flow cytometry. The results suggest a complex interplay between the induction of senescence and concurrent neuronal differentiation of SH SY5Y cells mediated by early alterations in SIRT1 and SIRT3. Thus, we report the senescence and differentiation potential of WS extracts and WA through ROS that are mediated via modulation of SIRT1, SIRT3 and mitochondria function.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"233 ","pages":"Pages 174-185"},"PeriodicalIF":7.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742745","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}
Ming-Ju Wu , Yu-Teng Chang , Tzu-Yi Chuang , Wang-Sheng Ko , Chih-Chiang Lu , Jeng-Jer Shieh
{"title":"Targeting mitophagy using isoliensinine as a therapeutic strategy for renal cell carcinoma treatment","authors":"Ming-Ju Wu , Yu-Teng Chang , Tzu-Yi Chuang , Wang-Sheng Ko , Chih-Chiang Lu , Jeng-Jer Shieh","doi":"10.1016/j.freeradbiomed.2025.03.037","DOIUrl":"10.1016/j.freeradbiomed.2025.03.037","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC) is a formidable and lethal form of kidney cancer, necessitating the exploration of novel therapeutic options. Isoliensinine, an alkaloid derived from lotus seed embryos, has shown promising anti-cancer properties. However, its mechanistic actions and impact on mitochondrial dynamics remain poorly understood. This research has aimed to investigate the effects of isoliensinine on RCC, as well as its potential involvement in mitophagy and mitochondrial function. In vitro experiments utilizing RCC cell lines (786-O and ACHN) have demonstrated that isoliensinine treatment significantly reduced cell viability. Moreover, isoliensinine induced an increase in cellular and mitochondrial reactive oxygen species (ROS) levels, accompanied by reduced mitochondria membrane potential, indicating an influence on mitochondrial function. Furthermore, MitoTracker staining revealed distinct mitochondrial morphologies, with isoliensinine promoting mitochondrial fission, thus supporting its role in mitochondrial dynamics. Notably, isoliensinine led to a time-dependent upregulation of mitophagy-related proteins, indicative of mitophagy activation. Of particular interest, the addition of MitoTEMPO, a potent mitochondrial ROS scavenger, effectively reversed the isoliensinine-induced upregulation of mitophagy-related protein expression and mitochondrial ROS levels. These combined results provide novel insight into the impact of isoliensinine-induced mitophagy on mitochondrial dynamics in renal carcinoma cells. Overall, the findings from this study highlight isoliensinine as a promising candidate with significant potential for further investigation and eventual clinical application in RCC therapy. Moreover, the modulation of mitochondrial dynamics, mitophagy and ROS levels through the use of isoliensinine further adds to its appeal as a potential therapeutic agent.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"233 ","pages":"Pages 132-147"},"PeriodicalIF":7.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729665","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}