Cell Stress最新文献

{"title":"Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.","authors":"Yiguo Zhang, Xi Chen, Meng Wang, Yuping Zhu, Wei Shi, Chao Li, Zhengwen Zhang, Hiroaki Taniguchi, Ping Ao","doi":"10.15698/cst2025.07.306","DOIUrl":"10.15698/cst2025.07.306","url":null,"abstract":"<p><p>Differential and even opposing functions of two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by <i>Nfe2l1</i> and <i>Nfe2l2</i>, respectively) are determined by distinctions in their tempospatial positioning, topological repartitioning, proteolytic processing, and biochemical modification, as well as in their shared evolutionary origin. As a matter of fact, the allelopathic potentials of Nrf1 and Nrf2 (both resembling two entangled 'Yin-Yang' quanta that comply with a dialectic law of the unity of opposites) are fulfilled to coordinately control redox physiological homeostasis so as to be maintained within the presetting thresholds. By putative exponential curves of redox stress and intrinsic anti-redox capability, there is inferable to exist a set point at approaching zero with the 'Golden Mean' for the healthy survival (i.e., dubbed the 'zero theory'). A bulk of the hitherto accumulating evidence demonstrates that the set point of redox homeostasis is dictated selectively by multi-hierarchical threshold settings, in which the living fossil-like Nrf1 acts as a robust indispensable determinon, whereas Nrf2 serves as a versatile chameleon-like master regulon, in governing the redox homeodynamic ranges. This is attributable to the facts that Nrf2 has exerted certain 'double-edged sword' effects on life process, whereas Nrf1 executes its essential physiobiological functions, along with unique pathophysiological phenotypes, by integrating its 'three-in-one' roles elicited as a specific triplet of direct sensor, transducer and effector within multi-hierarchical stress responsive signaling to redox metabolism and target gene reprogramming. Here, we also critically reviewed redox regulation of physio-pathological functions from the eco-evo-devo perspectives, through those coding rules (redox code, stress-coping code, and topogenetic code). The evolving concepts on stress and redox stress were also further revisited by scientific principles of physics and chemistry. Besides, several novel concepts such as oncoprotists, Reverse Central Dogma, and Grand Redox-Unifying Theory' (GRUT) of life, together with diffusive reactive species (DRS)-based murburn concept integrating all stochastic electron-, proton- and/or moiety-transfer reactive and interactive processes (e.g., PCHEMS), are introduced in this interdisciplinary and synthetic review.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"9 ","pages":"65-142"},"PeriodicalIF":4.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic aspects of fructose consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): A narrative review.","authors":"Katharina Burger, Michael Michael Trauner, Ina Bergheim","doi":"10.15698/cst2025.06.305","DOIUrl":"10.15698/cst2025.06.305","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to non-alcoholic fatty liver disease (NAFLD), has become a global health concern with a still increasing prevalence. One of the major contributing factors to its pathogenesis is overnutrition. In recent years, a discussion has been started that not only general overnutrition but also specific dietary patterns like the so-called 'Western diet' composed of foods rich in saturated fats, cholesterol, and sugar (especially fructose) but low in fiber and polyunsaturated fats, may contribute to the development of MASLD. Evidence from human (intervention) studies regarding the effects of sugar and especially fructose intake is limited and contradictory with respect to the development of MASLD. Still, some scientific liver societies have incorporated a reduction of sugar-sweetened beverages (SSBs) being rich in fructose in their life-style advice for the treatment of MASLD. Being metabolized independently of insulin, fructose has been proposed to be processed more rapidly than glucose, leading to increased lipogenesis and subsequently to hepatic lipid accumulation. Results of more recent experimental studies suggest that an elevated intake of fructose may also affect gut microbiota composition, alter small intestinal morphology and impair intestinal barrier function subsequently leading to an increased translocation of pathogen-associated molecular patterns (PAMPs) into the portal circulation. In this narrative review we summarize recent findings related to the relationship of fructose intake and MASLD, herein focusing on the gut-liver axis and the discrepancy between studies in humans and model organisms.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"9 ","pages":"49-64"},"PeriodicalIF":4.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFAT5: a stress-related transcription factor with multiple functions in health and disease.","authors":"Alfredo Domínguez-López, Fátima S Magaña-Guerrero, Beatriz Buentello-Volante, Óscar Vivanco-Rojas, Yonathan Garfias","doi":"10.15698/cst2025.05.304","DOIUrl":"10.15698/cst2025.05.304","url":null,"abstract":"<p><p>Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor within the Rel family, primarily recognized for its role in cellular adaptation to osmotic stress, particularly in hypertonic and hyperosmotic environments. Beyond osmotic regulation, NFAT5 responds to diverse stimuli, including cytokines, growth factors, oxidative stress, and microbial signals. This versatility enables NFAT5 to regulate essential cellular processes such as proliferation, survival, migration, and vascular remodelling. In the immune system, NFAT5 modulates the function of monocytes, macrophages, astrocytes, microglia, and T cells, contributing to immune homeostasis and inflammatory responses. Dysregulation of NFAT5 activity is implicated in various pathological conditions, including autoimmune diseases, cancer, and cardiovascular disorders, largely due to its ability to control genes involved in inflammatory and immune pathways under both isotonic and hypertonic conditions. Recent studies have unveiled new regulatory mechanisms, including interactions with non-coding RNAs, offering deeper insights into the functional landscape of NFAT5 and its therapeutic potential. This review delves into the multifaceted roles of NFAT5 in health and disease, emphasizing its emerging importance as a promising therapeutic target.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"9 ","pages":"16-48"},"PeriodicalIF":4.1,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotics and mediterranean diet for breast cancer management and prevention?","authors":"Ehssan A Sharif-Askari, Khadija M Atoui, Ali K Mteyrek, Lama M Fawaz","doi":"10.15698/cst2025.05.303","DOIUrl":"10.15698/cst2025.05.303","url":null,"abstract":"<p><p>The human gut microbiota, a diverse community of beneficial normal flora microorganisms, significantly influences physiological function and the immune response. Various microbiota strains have shown promise in supporting clinical treatment of chronic diseases, including cancer, by potentially providing antioxidative and anti-tumorigenic effects in both <i>in vivo</i> and <i>in vitro</i> studies. Breast cancer, which ranks amongst the top five cancer types common worldwide and particularly in Mediterranean countries, has been showing high incidence and prevalence. In breast cancer, microbiota composition, hormonal dynamics, and dietary choices are believed to play significant roles. Hence, the Mediterranean diet, known for its microbiota-friendly features, emerges as a potential protective factor against breast cancer development, highlighting the potential for personalized dietary strategies in cancer prevention. This comprehensive review highlights the emerging mechanisms by which probiotics support our immune system during different physiological activities. It also discusses their potential role, along with nutrition intervention, in improving essential clinical treatment outcomes in breast cancer patients and survivors, suggesting potential supportive strategies that go hand in hand with clinical strategies. Unfortunately, very little research addresses the possible clinical implications of probiotics and dietary habits on breast cancer, despite the promising results, calling for further studies and actions.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"9 ","pages":"1-15"},"PeriodicalIF":4.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold exposure reinstates NAD⁺ levels and attenuates hepatocellular carcinoma.","authors":"Tatiana P Grazioso, Maria Del Mar Rigual, Cristian Perna, Eduardo J Caleiras, Nabil Djouder","doi":"10.15698/cst2024.12.302","DOIUrl":"https://doi.org/10.15698/cst2024.12.302","url":null,"abstract":"<p><p>Cold exposure has been historically used for medicinal purposes, but its benefits and associated mechanisms in mammalian organisms still remain unclear. Here, we explore the chemoprotective properties of cold temperature using a mouse model of hepatocellular carcinoma (HCC) that recapitulates several human features. Chronic cold exposure is shown to prolong lifespan in diseased mice, enhance liver health, and suppress the development of aggressive HCC, preventing hepatocellular hypertrophy, high-grade oval cell hyperplasia, liver steatosis, and aberrant hepatocyte hyperproliferation. Mechanistically, exposure to cold temperatures reinstates NAD⁺ levels in the HCC mouse models that originally exhibited low NAD⁺ levels, a contributing process to the development of liver tumors. These findings uncover the role of cold therapy to attenuate HCC development and potentially other existing malignancies involving NAD⁺ modulation.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"8 ","pages":"125-139"},"PeriodicalIF":4.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous plasma resuspension of peripheral blood mononuclear cells prevents preparative-associated stress that modifies polyA-enriched RNA responses to subsequent acute stressors.","authors":"Dongyang Li, Karina Al-Dahleh, Daniel A Murphy, Sonya Georgieva, Nik Matthews, Claire L Shovlin","doi":"10.15698/cst2024.11.301","DOIUrl":"10.15698/cst2024.11.301","url":null,"abstract":"<p><p>Human peripheral blood mononuclear cells (PBMCs) are used to examine biological processes and disease, when basal variability in cellular activation and splicing is described and unexplained. Using isolation systems that maintained buffy coat cells (PBMCs, platelets) in their own plasma, poly-A enriched RNA-sequencing (RNASeq) detected 42,720 Ensembl gene IDs, including >95% of the top 100 Genotype Tissue Expression Project (GTEx)-expressed genes in lung, colon, heart, skeletal muscle and liver, and 10/17 clinically-actionable genes listed by the Pharmacogenomics Knowledgebase. Transcriptome changes were defined after 1h treatment with 32°C hypothermia (hsp70 family member change), 10 μmol/L ferric citrate that had no discernible effect, and 100 μg/mL cycloheximide leading to induction of primary response (immediate early) genes including IL1B and TNF. Same-donor PBMCs prepared conventionally using washes then resuspension in serum-supplemented media demonstrated basal upregulation of stress signalling pathway genes that masked and overlapped differential gene expression profiles after 100 µg/L cycloheximide. Plasma-resuspended PBMCs demonstrated minor transcriptome changes after 40 μmol/L ferric citrate, whereas consistent and greater magnitude changes were observed for washed/media-resuspended PBMCs. We conclude that endogenous plasma-maintained PBMCs provide a more robust platform to interrogate acute cellular perturbations triggering innate immunity, and that varying susceptibility of PBMCs to preparative stresses is an important component of experimental variability.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"11 ","pages":"112-124"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroglobin-enriched secretome provides neuroprotection against hydrogen peroxide and mitochondrial toxin-induced cellular stress.","authors":"Giovanna Bastari, Virginia Solar Fernandez, Maurizio Muzzi, Sandra Moreno, Maria Marino, Marco Fiocchetti","doi":"10.15698/cst2024.11.300","DOIUrl":"10.15698/cst2024.11.300","url":null,"abstract":"<p><p>Aberrant response to physiological cell stress is part of the mechanisms underlying the development of diverse human diseases, including neuropathologies. Neuroglobin (NGB), an intracellular monomeric globin, has gained attention for its role in endogenous stress response pathways in neuroprotection. To date, evidence supports the concept of NGB as an inducible protein, triggered by physiological and pathological stimuli via transcriptional and/or post-transcriptional mechanisms, offering cell-autonomous neuroprotective functions under various cellular stresses. Notably, recent evidence suggests the extracellular occurrence of NGB. We aimed to explore whether NGB redistribution in the cell microenvironment may serve in transmitting resilience capability in a model with neuronal characteristics. Results obtained in SH-SY5Y demonstrated that intracellular NGB upregulation is associated with the promotion of the extracellular release of the globin. Additionally, cell secretome from NGB-overexpressing cells, characterized by globin accumulation, exhibits protective effects against oxidative stress and mitochondrial toxicity, as evidenced by reduced apoptosis and preserved mitochondrial structure. These findings shed light on the potential significance of extracellular NGB as part of a common cell response to physiological and stress conditions and as a factor promoting cell resilience. Furthermore, the potential for neuroprotection of extracellular NGB paves the way for future therapeutic opportunities.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"8 ","pages":"99-111"},"PeriodicalIF":4.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress granules formation in HEI-OC1 auditory cells and in H4 human neuroglioma cells secondary to cisplatin exposure.","authors":"Hebatallah Abdelrasol, Avika Chopra, Liana Shvachiy, Dirk Beutner, Tiago F Outeiro, Cristian Setz","doi":"10.15698/cst2024.10.299","DOIUrl":"10.15698/cst2024.10.299","url":null,"abstract":"<p><p>Stress granules (SGs) are highly dynamic micromolecular membraneless condensates that generate in cells subjected to stress. Formed from pools of untranslating messenger ribonucleoproteins (RNP), SGs dynamics constitute vital processes essential for cell survival. Here, we investigate whether established cytotoxic agents, such as the platinum-based chemotherapeutic agent cisplatin and the aminoglycoside antibiotic gentamicin, elicit SG formation in the House Ear Institute-Organ of Corti-1 (HEI-OC1) auditory cell line, H4 human neuroglioma cells and HEK-293T human embryonic kidney cells. Cells were treated with cisplatin or gentamicin for specific durations at designated concentrations. SG formation was assessed using immunocytochemistry and live cell imaging. Levels of essential proteins involved in SG assembly were evaluated using immunoblotting. We observed cisplatin-associated SG assembly in HEI-OC1 and H4 cells via confocal microscopy through antibody colabeling of G3BP1 with PABP or Caprin1. While maintaining an unchanged pattern of expression of main constituent SG proteins, cisplatin-related SGs in H4 cells persisted for at least 12 h after drug removal. Cells subjected to gentamicin exposure did not exhibit SGs. Our findings offer insights into subcellular mechanisms related to cisplatin-associated cytotoxicity, highlighting the need for future studies to further investigate this stress-response mechanism.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"8 ","pages":"83-98"},"PeriodicalIF":4.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of cell membrane lesions and adaptive conductance under the electrical stress.","authors":"Mantas Silkunas, Olga N Pakhomova, Giedre Silkuniene, Andrei G Pakhomov","doi":"10.15698/cst2024.08.298","DOIUrl":"10.15698/cst2024.08.298","url":null,"abstract":"<p><p>Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca²⁺ entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a low 50- to 300-pS conductance, which disappeared instantly once the hyperpolarization was removed. Charging to -240 mV created high-conductance (> 1 nS) pores which persisted for seconds even at zero membrane potential. With incremental hyperpolarization steps, persistent pores often emerged at locations different from those where the short-lived, low-conductance pores or diffuse permeabilization were previously observed. Attempts to polarize membrane beyond the threshold for the formation of persistent pores increased their conductance adaptively, preventing further potential build-up and \"clamping\" it at a certain limit (-270 ± 6 mV in HEK cells, -284 ± 5 mV in CHO cells, and -243 ± 9 mV in neurons). The data suggest a previously unknown role of electroporative lesions as a protective mechanism against a potentially fatal membrane overcharging and cell disintegration.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"8 ","pages":"69-82"},"PeriodicalIF":4.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment.","authors":"Vincent Géli, Norbert Nabet","doi":"10.15698/cst2024.05.297","DOIUrl":"10.15698/cst2024.05.297","url":null,"abstract":"<p><p>For many diseases, and cancer in particular, early diagnosis allows a wider range of therapies and a better disease management. This has led to improvements in diagnostic procedures, most often based on tissue biopsies or blood samples. Other biological fluids have been used to diagnose disease, and among them saliva offers a number of advantages because it can be collected non-invasively from large populations at relatively low cost. To what extent might saliva content reveal the presence of a tumour located at a distance from the oral cavity and the molecular information obtained from saliva be used to establish a diagnosis are current questions. This review focuses primarily on the content of saliva and shows how it potentially offers a source of diagnosis, possibly at an early stage, for pathologies such as cancers or endometriosis.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"8 ","pages":"59-68"},"PeriodicalIF":6.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11144459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}