Life sciences最新文献

ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-18 DOI: 10.1016/j.lfs.2025.123565

Tao Li , Ningning Wang , Dongxin Yi , Yuji Xiao , Xiao Li , Bing Shao , Ziyi Wu , Jie Bai , Xiaoxia Shi , Chenbing Wu , Tianming Qiu , Guang Yang , Xiance Sun , Rongfeng Zhang

The cardiomyocyte is an essential component of the heart, communicating and coordinating with non-cardiomyocytes (endothelial cells, fibroblasts, and immune cells), and are critical for the regulation of structural deformation, electrical conduction, and contractile properties of healthy and remodeled myocardium. Reactive oxygen species (ROS) in cardiomyocytes are mainly produced by the mitochondrial oxidative respiratory chain, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), xanthine oxidoreductase (XOR), monoamine oxidase (MAO), and p66shc. Under physiological conditions, ROS are involved in the regulation of cardiac development and cardiomyocyte maturation, cardiac calcium handling, and excitation-contraction coupling. In contrast, dysregulation of ROS metabolism is involved in the development and progression of cardiovascular diseases (CVDs), including myocardial hypertrophy, hyperlipidemia, myocardial ischemia/reperfusion injury, arrhythmias and diabetic cardiomyopathy. Further oxidative stress induced by ROS dyshomeostasis was found to be the major reason for cardiomyocyte death in cardiac diseases, and in recent years, ferroptosis induced by oxidative stress have been considered to be fatal to cardiomyocytes. In addition, ROS is also a key trigger for the activation of pyroptosis, which induces and exacerbates the inflammatory response caused by various cardiac diseases and plays a critical role in CVDs. Therefore, in this review, the sources and destinations of ROS in cardiomyocytes will be systematically addressed, so as to reveal the molecular mechanisms by which ROS accumulation triggers cardiomyocyte ferroptosis and pyroptosis under pathological conditions, and provide a new concept for the research and treatment of heart-related diseases.

{"title":"ROS-mediated ferroptosis and pyroptosis in cardiomyocytes: An update","authors":"Tao Li , Ningning Wang , Dongxin Yi , Yuji Xiao , Xiao Li , Bing Shao , Ziyi Wu , Jie Bai , Xiaoxia Shi , Chenbing Wu , Tianming Qiu , Guang Yang , Xiance Sun , Rongfeng Zhang","doi":"10.1016/j.lfs.2025.123565","DOIUrl":"10.1016/j.lfs.2025.123565","url":null,"abstract":"<div><div>The cardiomyocyte is an essential component of the heart, communicating and coordinating with non-cardiomyocytes (endothelial cells, fibroblasts, and immune cells), and are critical for the regulation of structural deformation, electrical conduction, and contractile properties of healthy and remodeled myocardium. Reactive oxygen species (ROS) in cardiomyocytes are mainly produced by the mitochondrial oxidative respiratory chain, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), xanthine oxidoreductase (XOR), monoamine oxidase (MAO), and p66shc. Under physiological conditions, ROS are involved in the regulation of cardiac development and cardiomyocyte maturation, cardiac calcium handling, and excitation-contraction coupling. In contrast, dysregulation of ROS metabolism is involved in the development and progression of cardiovascular diseases (CVDs), including myocardial hypertrophy, hyperlipidemia, myocardial ischemia/reperfusion injury, arrhythmias and diabetic cardiomyopathy. Further oxidative stress induced by ROS dyshomeostasis was found to be the major reason for cardiomyocyte death in cardiac diseases, and in recent years, ferroptosis induced by oxidative stress have been considered to be fatal to cardiomyocytes. In addition, ROS is also a key trigger for the activation of pyroptosis, which induces and exacerbates the inflammatory response caused by various cardiac diseases and plays a critical role in CVDs. Therefore, in this review, the sources and destinations of ROS in cardiomyocytes will be systematically addressed, so as to reveal the molecular mechanisms by which ROS accumulation triggers cardiomyocyte ferroptosis and pyroptosis under pathological conditions, and provide a new concept for the research and treatment of heart-related diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123565"},"PeriodicalIF":5.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143654887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CKN reduces TLR4-mediated inflammation and cerebral I/R injury by activating the LXRα/ABCA1 pathway in microglia.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-17 DOI: 10.1016/j.lfs.2025.123571

Xuejiao Lei, Xiaodong Ran, Jiawei Wang, Lin Li, Niting Wu, Xufang Ru, Pengbo Wang, Xiaohui Li, Wenyan Li, Yan Huang

Aims: CKN is a self-developed LXRα agonist capable of up-regulating the expression of ABCA1, diminishing intracellular lipid deposition, and attenuating the inflammatory response. Nevertheless, the protective effect and mechanism of ischemic stroke remain indistinct. The aim of this study is to investigate the therapeutic effects and the underlying mechanisms of CKN in ischemic stroke.

Materials and methods: In this study, the tMCAO model was utilized to induce cerebral artery occlusion in mice, and cholesterol-induced BV2 and primary microglia models were adopted. Neuronal damage and the effect of CKN on ABCA1 expression, lipid deposition, and TLR4 signaling in penumbra microglia were assessed.

Key findings: The results demonstrated that: (1) CKN treatment markedly ameliorated the neurological deficit score of the tMCAO model, contracted the infarct size, and mitigated the damage of the cerebral cortex. (2) CKN has the capacity to up-regulate the expression of ABCA1 in microglia within the ischemic penumbra by activating the LXRα/ABCA1 signaling pathway, and minimize lipid deposition and inflammatory responses. (3) The activation of the LXRα/ABCA1 signaling pathway is profoundly implicated in the inflammatory response triggered by CKN inhibition of the TLR4 signaling pathway in microglia.

Significance: The present study demonstrated for the first time that the activation of the LXRα/ABCA1 signaling possessed the ability to attenuate reperfusion injury in ischemic stroke by means of reducing lipid droplet formation and TLR4-mediated inflammatory signaling within microglia in the ischemic penumbra.

{"title":"CKN reduces TLR4-mediated inflammation and cerebral I/R injury by activating the LXRα/ABCA1 pathway in microglia.","authors":"Xuejiao Lei, Xiaodong Ran, Jiawei Wang, Lin Li, Niting Wu, Xufang Ru, Pengbo Wang, Xiaohui Li, Wenyan Li, Yan Huang","doi":"10.1016/j.lfs.2025.123571","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123571","url":null,"abstract":"<p><strong>Aims: </strong>CKN is a self-developed LXRα agonist capable of up-regulating the expression of ABCA1, diminishing intracellular lipid deposition, and attenuating the inflammatory response. Nevertheless, the protective effect and mechanism of ischemic stroke remain indistinct. The aim of this study is to investigate the therapeutic effects and the underlying mechanisms of CKN in ischemic stroke.</p><p><strong>Materials and methods: </strong>In this study, the tMCAO model was utilized to induce cerebral artery occlusion in mice, and cholesterol-induced BV2 and primary microglia models were adopted. Neuronal damage and the effect of CKN on ABCA1 expression, lipid deposition, and TLR4 signaling in penumbra microglia were assessed.</p><p><strong>Key findings: </strong>The results demonstrated that: (1) CKN treatment markedly ameliorated the neurological deficit score of the tMCAO model, contracted the infarct size, and mitigated the damage of the cerebral cortex. (2) CKN has the capacity to up-regulate the expression of ABCA1 in microglia within the ischemic penumbra by activating the LXRα/ABCA1 signaling pathway, and minimize lipid deposition and inflammatory responses. (3) The activation of the LXRα/ABCA1 signaling pathway is profoundly implicated in the inflammatory response triggered by CKN inhibition of the TLR4 signaling pathway in microglia.</p><p><strong>Significance: </strong>The present study demonstrated for the first time that the activation of the LXRα/ABCA1 signaling possessed the ability to attenuate reperfusion injury in ischemic stroke by means of reducing lipid droplet formation and TLR4-mediated inflammatory signaling within microglia in the ischemic penumbra.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123571"},"PeriodicalIF":5.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LKB1 activated by NaB inhibits the IL-4/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization NaB 激活的 LKB1 可抑制 IL-4/STAT6 轴，并通过抑制 M2 巨噬细胞极化改善肾脏纤维化。

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-15 DOI: 10.1016/j.lfs.2025.123564

Weifei Liang , Haoyu Wu , Qishan Long , Hong Lin , Xiaoyu Lv , Wen Ma , Tao Wu , Ai Li , Qingyou Zheng , Jinan Guo , Xiangqiu Chen , Jing Guo , Donglin Sun

Background

Renal fibrosis is a critical pathological characteristic of chronic kidney disease, and current antifibrotic therapies has limited efficacy. Sodium butyrate (NaB) has been shown to be highly effective in mitigating bleomycin-induced pulmonary fibrosis; however, its specific impact on renal fibrosis and the underlying mechanisms remain unclear. This study aims to elucidate the role and mechanism of NaB in renal fibrosis by using a mouse model of renal fibrosis induced through Unilateral Ureteral Obstruction (UUO) and folic acid (FA) administration.

Results

NaB significantly decreased the distribution of collagen fibers in renal tissues and mitigated fibrosis in a dose-dependent manner. Further analysis indicated that NaB inhibited M2 macrophage polarization in the renal tissues of UUO model mice by blocking the phosphorylation of STAT6, hence reducing renal fibrosis. Additionally, in vitro experiments demonstrated that NaB inhibited fibroblast activation induced by M2 macrophages. Mechanistic studies revealed that NaB attenuates fibroblast activation and M2 macrophage polarization by upregulating LKB1 and inhibiting the activation of the STAT6 signaling pathway.

Conclusion

NaB may exert its effects by inhibiting the activation of the IL-4/STAT6 signaling pathway through the upregulation of LKB1, which suppress the polarization of M2 macrophages and consequently reduce renal fibrosis. These findings establish a theoretical foundation for NaB as a novel drug candidate for renal fibrosis and indicate its potential applicability in clinical treatments for this condition.

{"title":"LKB1 activated by NaB inhibits the IL-4/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization","authors":"Weifei Liang , Haoyu Wu , Qishan Long , Hong Lin , Xiaoyu Lv , Wen Ma , Tao Wu , Ai Li , Qingyou Zheng , Jinan Guo , Xiangqiu Chen , Jing Guo , Donglin Sun","doi":"10.1016/j.lfs.2025.123564","DOIUrl":"10.1016/j.lfs.2025.123564","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis is a critical pathological characteristic of chronic kidney disease, and current antifibrotic therapies has limited efficacy. Sodium butyrate (NaB) has been shown to be highly effective in mitigating bleomycin-induced pulmonary fibrosis; however, its specific impact on renal fibrosis and the underlying mechanisms remain unclear. This study aims to elucidate the role and mechanism of NaB in renal fibrosis by using a mouse model of renal fibrosis induced through Unilateral Ureteral Obstruction (UUO) and folic acid (FA) administration.</div></div><div><h3>Results</h3><div>NaB significantly decreased the distribution of collagen fibers in renal tissues and mitigated fibrosis in a dose-dependent manner. Further analysis indicated that NaB inhibited M2 macrophage polarization in the renal tissues of UUO model mice by blocking the phosphorylation of STAT6, hence reducing renal fibrosis. Additionally, in vitro experiments demonstrated that NaB inhibited fibroblast activation induced by M2 macrophages. Mechanistic studies revealed that NaB attenuates fibroblast activation and M2 macrophage polarization by upregulating LKB1 and inhibiting the activation of the STAT6 signaling pathway.</div></div><div><h3>Conclusion</h3><div>NaB may exert its effects by inhibiting the activation of the IL-4/STAT6 signaling pathway through the upregulation of LKB1, which suppress the polarization of M2 macrophages and consequently reduce renal fibrosis. These findings establish a theoretical foundation for NaB as a novel drug candidate for renal fibrosis and indicate its potential applicability in clinical treatments for this condition.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123564"},"PeriodicalIF":5.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic reprogramming and synergistic cytotoxicity of genistein and chemotherapy in human breast cancer cells

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-14 DOI: 10.1016/j.lfs.2025.123562

Sandra Tobón-Cornejo , Ariana Vargas-Castillo , Mandy Juarez , Joshua Ayork Acevedo-Carabantes , Lilia G. Noriega , Omar Granados-Portillo , Alma Chávez-Blanco , Rocío Morales-Bárcenas , Nimbe Torres , Armando R. Tovar , Alejandro Schcolnik-Cabrera

Breast cancer (BCa) is a heterogeneous disease, initially responsive to hormone therapy but often developing resistance to both hormonal and chemotherapy treatments. Novel therapeutic strategies are needed for drug-resistant BCa. Genistein, a phytoestrogen structurally similar to estrogen, competes with estrogen for receptor binding and exhibits anti-cancer effects. In this study, we investigated the cellular and metabolic impacts of genistein, alone or in combination with chemotherapy, in two human BCa cell lines—one estrogen receptor-positive (ER+) and one estrogen receptor-negative (ER−). We observed a strong synergistic effect on cell viability at low concentrations of genistein and chemotherapy, resulting in reduced clonogenic capacity and impaired cell migration. Genistein alone modulated cellular energy metabolism, notably reducing ATP production in MCF7 (ER+) cells. This metabolic shift was linked to a decreased dependence on fatty acids for energy, coupled with a decrease in the rate-limiting mitochondrial translocase CPT1 required for fatty acid oxidation, alongside with an increase in intracellular fatty acid levels. While the most significant changes occurred in ER+ cells, ER− cells also showed responses to genistein treatment. Collectively, our findings suggest that low genistein concentrations, in combination with conventional chemotherapy, induces synergistic anti-cancer effects, promoting cellular senescence.

乳腺癌（BCa）是一种异质性疾病，最初对激素治疗有反应，但往往会对激素和化疗产生耐药性。对于耐药的乳腺癌，需要新的治疗策略。染料木素是一种在结构上与雌激素相似的植物雌激素，它能与雌激素竞争受体结合，具有抗癌作用。在这项研究中，我们研究了染料木素单独或与化疗相结合对两种人类 BCa 细胞系--一种是雌激素受体阳性（ER+）细胞系，另一种是雌激素受体阴性（ER-）细胞系--的细胞和代谢影响。我们观察到，低浓度的染料木素和化疗对细胞活力有很强的协同作用，导致细胞的克隆生成能力降低，细胞迁移能力受损。单用染料木素可调节细胞的能量代谢，特别是减少 MCF7（ER+）细胞的 ATP 生成。这种新陈代谢变化与对脂肪酸能量的依赖性降低、脂肪酸氧化所需的线粒体限速转运酶 CPT1 减少以及细胞内脂肪酸水平升高有关。虽然最明显的变化发生在ER+细胞中，但ER-细胞也对染料木素处理有反应。总之，我们的研究结果表明，低浓度的染料木素与传统化疗相结合，可诱导协同抗癌效应，促进细胞衰老。

{"title":"Metabolic reprogramming and synergistic cytotoxicity of genistein and chemotherapy in human breast cancer cells","authors":"Sandra Tobón-Cornejo , Ariana Vargas-Castillo , Mandy Juarez , Joshua Ayork Acevedo-Carabantes , Lilia G. Noriega , Omar Granados-Portillo , Alma Chávez-Blanco , Rocío Morales-Bárcenas , Nimbe Torres , Armando R. Tovar , Alejandro Schcolnik-Cabrera","doi":"10.1016/j.lfs.2025.123562","DOIUrl":"10.1016/j.lfs.2025.123562","url":null,"abstract":"<div><div>Breast cancer (BCa) is a heterogeneous disease, initially responsive to hormone therapy but often developing resistance to both hormonal and chemotherapy treatments. Novel therapeutic strategies are needed for drug-resistant BCa. Genistein, a phytoestrogen structurally similar to estrogen, competes with estrogen for receptor binding and exhibits anti-cancer effects. In this study, we investigated the cellular and metabolic impacts of genistein, alone or in combination with chemotherapy, in two human BCa cell lines—one estrogen receptor-positive (ER+) and one estrogen receptor-negative (ER−). We observed a strong synergistic effect on cell viability at low concentrations of genistein and chemotherapy, resulting in reduced clonogenic capacity and impaired cell migration. Genistein alone modulated cellular energy metabolism, notably reducing ATP production in MCF7 (ER+) cells. This metabolic shift was linked to a decreased dependence on fatty acids for energy, coupled with a decrease in the rate-limiting mitochondrial translocase CPT1 required for fatty acid oxidation, alongside with an increase in intracellular fatty acid levels. While the most significant changes occurred in ER+ cells, ER− cells also showed responses to genistein treatment. Collectively, our findings suggest that low genistein concentrations, in combination with conventional chemotherapy, induces synergistic anti-cancer effects, promoting cellular senescence.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123562"},"PeriodicalIF":5.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Critical role of microRNAs in cellular quality control during brain aging and neurological disorders: Interplay between autophagy and proteostasis

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-13 DOI: 10.1016/j.lfs.2025.123563

Rajesh Tamatta, Abhishek Kumar Singh

A decline in cellular quality control mechanisms is one of the processes of brain aging. Autophagy and proteostasis are two regulatory mechanisms that maintain cellular component turnover to preserve cellular homeostasis, optimal function, and neuronal health by eliminating damaged and aggregated proteins and preventing neurodegenerative disorders (NDDs). Impaired autophagy and proteostasis are significant hallmarks of aging and many age-related NDDs. MicroRNAs are noncoding RNA molecules that have recently been shown to be essential for regulating several biological processes, such as autophagy, proteostasis, cellular differentiation, and development by targeting mRNA's 3’untranslated region (3’UTR). During brain aging, miRNAs have been shown to dysregulate proteostasis and autophagy, resulting in abnormal cellular activity and protein aggregation, a characteristic of age-related NDDs. This review highlights the complex interactions of miRNAs in the orchestration of proteostasis and autophagy. This dysregulation impairs autophagic flux and proteostasis and accelerates age-related disorders, neuroinflammation, and neurodegeneration. Understanding the complex interactions among miRNAs, autophagy, and proteostasis in the aging brain is essential for novel therapeutics development for age-related NDDs.

{"title":"Critical role of microRNAs in cellular quality control during brain aging and neurological disorders: Interplay between autophagy and proteostasis","authors":"Rajesh Tamatta, Abhishek Kumar Singh","doi":"10.1016/j.lfs.2025.123563","DOIUrl":"10.1016/j.lfs.2025.123563","url":null,"abstract":"<div><div>A decline in cellular quality control mechanisms is one of the processes of brain aging. Autophagy and proteostasis are two regulatory mechanisms that maintain cellular component turnover to preserve cellular homeostasis, optimal function, and neuronal health by eliminating damaged and aggregated proteins and preventing neurodegenerative disorders (NDDs). Impaired autophagy and proteostasis are significant hallmarks of aging and many age-related NDDs. MicroRNAs are noncoding RNA molecules that have recently been shown to be essential for regulating several biological processes, such as autophagy, proteostasis, cellular differentiation, and development by targeting mRNA's 3’untranslated region (3’UTR). During brain aging, miRNAs have been shown to dysregulate proteostasis and autophagy, resulting in abnormal cellular activity and protein aggregation, a characteristic of age-related NDDs. This review highlights the complex interactions of miRNAs in the orchestration of proteostasis and autophagy. This dysregulation impairs autophagic flux and proteostasis and accelerates age-related disorders, neuroinflammation, and neurodegeneration. Understanding the complex interactions among miRNAs, autophagy, and proteostasis in the aging brain is essential for novel therapeutics development for age-related NDDs.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123563"},"PeriodicalIF":5.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel function for exosomes in depression

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-13 DOI: 10.1016/j.lfs.2025.123558

Qingying Yu , Shuyi Ye , Mengxue Chen , Peng Sun , Ning Weng

Exosomes are a class of extracellular vesicles that encompass a diverse array of bioactive molecules, including proteins, lipids, mRNA, and microRNA(miRNA). Virtually all cell types release exosomes under both physiological and pathological conditions. In addition to electrical and chemical signals, exosomes are an alternative route of signaling between cells in the brain. In the brain, they are involved in processes such as synaptic plasticity, neuronal stress response, intercellular communication, and neurogenesis. A number of studies have shown that exosomes regulate the occurrence and development of depression by participating in the regulation of hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, immune inflammatory response and other mechanisms, showing that they may become potential biological agents for the diagnosis and treatment of depression. In addition, exosomes have the ability to easily cross the blood-brain barrier, making them ideal drug or molecular delivery tools for the central nervous system. Engineered exosomes have good brain targeting ability, and their research in central nervous system diseases has begun to emerge. However, the molecular pathways involved in the pathogenesis of depression remain unknown, and further studies are needed to fully understand the role of exosomes in the development or improvement of depression. Therefore, in this review, we mainly focus on the diagnostic performance and therapeutic effect of exosomes in depression, and explore the advantages of exosomes as biomarkers and gene delivery vectors for depression.

{"title":"A novel function for exosomes in depression","authors":"Qingying Yu , Shuyi Ye , Mengxue Chen , Peng Sun , Ning Weng","doi":"10.1016/j.lfs.2025.123558","DOIUrl":"10.1016/j.lfs.2025.123558","url":null,"abstract":"<div><div>Exosomes are a class of extracellular vesicles that encompass a diverse array of bioactive molecules, including proteins, lipids, mRNA, and microRNA(miRNA). Virtually all cell types release exosomes under both physiological and pathological conditions. In addition to electrical and chemical signals, exosomes are an alternative route of signaling between cells in the brain. In the brain, they are involved in processes such as synaptic plasticity, neuronal stress response, intercellular communication, and neurogenesis. A number of studies have shown that exosomes regulate the occurrence and development of depression by participating in the regulation of hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, immune inflammatory response and other mechanisms, showing that they may become potential biological agents for the diagnosis and treatment of depression. In addition, exosomes have the ability to easily cross the blood-brain barrier, making them ideal drug or molecular delivery tools for the central nervous system. Engineered exosomes have good brain targeting ability, and their research in central nervous system diseases has begun to emerge. However, the molecular pathways involved in the pathogenesis of depression remain unknown, and further studies are needed to fully understand the role of exosomes in the development or improvement of depression. Therefore, in this review, we mainly focus on the diagnostic performance and therapeutic effect of exosomes in depression, and explore the advantages of exosomes as biomarkers and gene delivery vectors for depression.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123558"},"PeriodicalIF":5.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-12 DOI: 10.1016/j.lfs.2025.123559

Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in a more exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid lineage-specific IFN-I response was essential in safeguarding against periodontal inflammation by suppressing the IL-17-producing γδ T cells in the gingiva. IFN-I signaling also directly repressed osteoclastogenesis in monocytes, which are precursor cells for osteoclasts. Therefore, our findings demonstrate that an integral myeloid-specific IFN-I pathway plays a protective role against bone loss by keeping the IL-17-neutrophil axis in check and directly inhibiting osteoclast formation in periodontitis.

{"title":"Type I interferon protects against bone loss in periodontitis by mitigating an interleukin (IL)-17-neutrophil axis.","authors":"Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang","doi":"10.1016/j.lfs.2025.123559","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123559","url":null,"abstract":"<p><p>Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in a more exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid lineage-specific IFN-I response was essential in safeguarding against periodontal inflammation by suppressing the IL-17-producing γδ T cells in the gingiva. IFN-I signaling also directly repressed osteoclastogenesis in monocytes, which are precursor cells for osteoclasts. Therefore, our findings demonstrate that an integral myeloid-specific IFN-I pathway plays a protective role against bone loss by keeping the IL-17-neutrophil axis in check and directly inhibiting osteoclast formation in periodontitis.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123559"},"PeriodicalIF":5.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Testes-specific protease 50 heightens stem-like properties and improves mitochondrial function in colorectal cancer

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-12 DOI: 10.1016/j.lfs.2025.123560

Feng Gao , Sichen Liu , Yue Sun , Chunlei Yu , Lihua Zheng , Luguo Sun , Guannan Wang , Ying Sun , Yongli Bao , Zhenbo Song , Xiaoguang Yang , Chao Ke

Aims

The progression of colorectal cancer (CRC) is driven by a small subset of cancer stem-like cells (CSCs), and mitochondrial function is essential for maintaining their stemness. TSP50, a novel identified oncogene, has been found to promote cell proliferation in multiple cancer types. In this study, we detected the regulatory role of TSP50 in regulating CSC-like properties and mitochondrial mass in CRC.

Materials and methods

First, TSP50 expression and clinical relevance were analyzed via clinical databases and immunohistochemical (IHC). Subsequently, bioinformatic analyses, CRC cell lines, tumorsphere cultures, and mouse xenograft models were utilized to evaluate the relationship between TSP50 and CSC-like properties as well as mitochondrial mass. Finally, immunofluorescence, immunoprecipitation, and Western blotting were performed to dissect the regulatory mechanisms of TSP50, followed by rescue experiments conducted both in vitro and in vivo.

Key findings

TSP50 was overexpressed in CRC tissues, correlating with poor drug response and shorter overall survival (OS). Meanwhile, TSP50 was shown to enhance CSC-like properties in both CRC cells and mouse xenograft models, while concurrently increasing mitochondrial mass and reducing ROS levels, these effects were partially reversed by inhibition of the PI3K/AKT pathway. Mechanistic investigations revealed that TSP50-induced activation of PI3K/AKT signaling is primarily mediated by the enhanced catalytic activity of PI3K p110α subunit.

Significance

Collectively, TSP50 drives CRC malignancy by promoting CSC-like properties and enhancing mitochondrial function through PI3K/AKT signaling. These findings identify TSP50 as a potential therapeutic target for eliminating CSC-like cells and improving clinical outcomes in CRC treatment.

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引用次数: 0

Bifidobacterium bifidum 1007478 derived indole-3-lactic acid alleviates NASH via an aromatic hydrocarbon receptor-dependent pathway in zebrafish

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-10 DOI: 10.1016/j.lfs.2025.123557

Chao Tian , Shizhou Deng , Zhao Zhang , Kangdi Zheng , Lai Wei

Aims

This study investigates the potential of Bifidobacterium bifidum 1007478 (BB478) and its metabolite indole-3-lactic acid (ILA) in alleviating non-alcoholic steatohepatitis (NASH) induced by a high-fat diet (HFD) and fructose exposure.

Materials and methods

A zebrafish model of NASH was established by exposure to HFD and fructose. BB478 was administered, and the effects on liver lipid accumulation, oxidative stress, and inflammation were assessed. ILA production by BB478 was confirmed, and its impact on hepatic lipogenesis and inflammatory pathways was evaluated. The involvement of the aromatic hydrocarbon receptor (AhR) was also examined using an AhR inhibitor.

Key findings

BB478 supplementation inhibited lipid accumulation in the liver, reduced triglycerides (TG) and total cholesterol (TC), and mitigated oxidative stress, as evidenced by lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA). ILA, produced by BB478, could alleviate the hepatic damage and fat deposition in liver. Mechanistically, it suppressed hepatic lipogenesis by downregulating lipogenesis-related genes, including sterol response element binding protein 1 (SREBP1) and fatty acid synthase (FASN). ILA also inhibited the expression of pro-inflammatory cytokines to suppress inflammation. The therapeutic effects of ILA were reversed by the AhR inhibitor, indicating that ILA's actions are AhR-dependent.

Significance

These findings reveal the potential of ILA, produced by Bifidobacterium bifidum, as a therapeutic agent for NASH. The mechanistic insights into AhR-mediated effects provide a foundation for further exploration of ILA as a novel approach for managing liver diseases.

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引用次数: 0

Corrigendum to "Aging-related hyperphosphatemia triggers the release of TNF-α from macrophages, promoting indicators of sarcopenia through the reduction of IL-15 expression in skeletal muscle" [Life Sci. 368 (2025) 123507].

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-03-10 DOI: 10.1016/j.lfs.2025.123550

Elena Alcalde-Estévez, Ariadna Moreno-Piedra, Ana Asenjo-Bueno, María Martos-Elvira, Mariano de la Serna-Soto, Marta Ruiz-Ortega, Gemma Olmos, Susana López-Ongil, María P Ruiz-Torres

引用次数: 0