Life sciences最新文献

{"title":"Betulinaldehyde regulates VSMC phenotypic transition to alleviate vascular hyperplasia through PPARγ/mitochondria/ROS axis","authors":"Xia Wang ,&nbsp;Yangxia Fu ,&nbsp;Huilin Xu ,&nbsp;Huilin Lian ,&nbsp;Siyi Zhang ,&nbsp;Songhua Chen ,&nbsp;Ziwei Liu ,&nbsp;Ren Guo","doi":"10.1016/j.lfs.2025.124002","DOIUrl":"10.1016/j.lfs.2025.124002","url":null,"abstract":"<div><h3>Aims</h3><div>Betulinaldehyde (BA) demonstrates various biological activities both in vivo and in vitro, but its role in vascular remodeling has been little explored. Our network pharmacological analysis suggests that PPARγ serves as a significant regulatory target for BA. This study seeks to clarify the mechanisms associated with BA, thereby offering new perspective targets for addressing vascular remodeling.</div></div><div><h3>Materials and methods</h3><div>Network pharmacology analysis identified key genes linking BA to vascular remodeling. In vivo effects of BA were evaluated by H&amp;E, immunohistochemical (IHC), and Masson staining. Vascular smooth muscle cells (VSMCs) function was examined using Western blotting, EdU incorporation, wound healing, and transwell assays. Mitochondrial alterations were assessed via electron microscopy, along with JC-1, ROS, and mitoSOX detection.</div></div><div><h3>Key findings</h3><div>In vivo experiments demonstrated that BA effectively alleviates intimal hyperplasia, collagen deposition, and the increase in the proliferation marker PCNA. Furthermore, BA effectively inhibits VSMC proliferation and migration induced by PDGF-BB. We further found that BA exerts its effects by regulating mitochondrial function through increasing PPARγ expression, which reduces ROS release and ultimately inhibits the progression of vascular remodeling. However, the inhibition or downregulation of PPARγ partially diminishes the therapeutic effects of BA, highlighting its crucial role in this process.</div></div><div><h3>Significance</h3><div>Our study suggests that BA mitigates vascular remodeling through PPARγ/mitochondria/ROS axis, which uncovers a novel mechanism linking BA to vascular remodeling. And BA's incentive function on PPARγ broadens its application in other diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 124002"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206818","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}

{"title":"CEACAM7 enhances oral cancer metastasis by upregulating CD317 expression","authors":"Chun-Wen Su ,&nbsp;Wei-En Yang ,&nbsp;Yi-Hsien Hsieh ,&nbsp;Chih-Hsin Tang ,&nbsp;Chiao-Wen Lin ,&nbsp;Shun-Fa Yang","doi":"10.1016/j.lfs.2025.123998","DOIUrl":"10.1016/j.lfs.2025.123998","url":null,"abstract":"<div><h3>Aims</h3><div>Carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) is involved in the regulation of normal cell differentiation. Although numerous studies have demonstrated a strong association between CEACAM7 expression and cancer progression, its specific role in the development and metastasis of oral cancer remains largely uncharacterized.</div></div><div><h3>Materials and methods</h3><div>Using RNA sequencing technology, transwell migration/invasion assays, western blotting, luciferase reporter, quantitative reverse transcription–polymerase chain reaction (qRT-PCR), and a xenograft model, the effects of CEACAM7 on cell migration in human oral cancer cells were investigated.</div></div><div><h3>Key findings</h3><div>In this study, analysis of the Gene Expression Omnibus (GEO) database revealed that patients with advanced-stage oral cancer or lymph node metastasis exhibited significantly elevated CEACAM7 expression, which correlated with poorer overall survival. RNA sequencing data further indicated that CEACAM7 overexpression upregulated the expression of CD317. Functional assays showed that CD317 overexpression enhanced the migratory capacity of oral cancer cells, whereas CD317 knockdown suppressed it. Pharmacological inhibition using JNK-IN-8 and PP1 suggested that CEACAM7 may regulate CD317 expression and cell migration via the phosphorylated JNK (p-JNK) and Src (p-Src) signaling pathways. The critical roles of CEACAM7 and CD317 in oral cancer metastasis were further validated using CEACAM7-stable cell lines, in vivo animal experiments, and clinical tissue specimens.</div></div><div><h3>Significance</h3><div>These findings suggest that CEACAM7 promotes oral cancer metastasis by regulating CD317 through the p-JNK and p-Src pathways. CEACAM7 and CD317 may therefore represent potential therapeutic targets for the treatment of metastatic oral cancer.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123998"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206794","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}

{"title":"AhR in biological processes of adipocytes and lipid metabolism in obesity: Friend and foe.","authors":"Xiaoya Li, Shengchen Wang, Xiaoshuang Mao, Meirong Fang, Xingyu Liu, Jingyi Jiang, Wen Jin","doi":"10.1016/j.lfs.2025.123996","DOIUrl":"10.1016/j.lfs.2025.123996","url":null,"abstract":"<p><p>Although the molecular mechanisms underlying dysregulation in adipocyte biological processes and lipid metabolism during obesity have been extensively studied, the limited therapeutic strategies developed thus far suggest that additional critical mechanisms influence obesity progression. Initially identified as a key mediator of environmental pollutant toxicity, the aryl hydrocarbon receptor (AhR) has garnered widespread attention in cancer and immune diseases due to its immunomodulatory functions. Recent studies have also revealed its involvement in metabolic disorders such as obesity. Notably, similar to findings in other diseases, AhR exerts complex and context-dependent roles in adipocyte biology and lipid metabolism during obesity. Based on a comprehensive review of the AhR signaling pathway, this manuscript systematically examines the roles of AhR in adipocyte differentiation, lipid metabolism, as well as thermogenesis in brown adipocytes. The objective is to elucidate the pathophysiological contributions of AhR to obesity development and progression, thereby establishing a theoretical foundation for mechanistic investigations and therapeutic interventions targeting obesity.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123996"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182116","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}

{"title":"2-Hydroxychalcone is a gonococcal-specific antimicrobial with activity against elongation factor Tu and butanediol dehydrogenase","authors":"Jianglin Zhang ,&nbsp;Fan Yang ,&nbsp;Xia Sun ,&nbsp;Lingyu Gao ,&nbsp;Jing Yan ,&nbsp;Xiuxian Chen ,&nbsp;Yuhua Gu ,&nbsp;Shuaijie Song ,&nbsp;Fuliang Hu ,&nbsp;Xu'ai Lin ,&nbsp;Simon Duttwyler ,&nbsp;Hao Cheng ,&nbsp;Stijn van der Veen","doi":"10.1016/j.lfs.2025.123994","DOIUrl":"10.1016/j.lfs.2025.123994","url":null,"abstract":"<div><h3>Aims</h3><div>This study explored botanical extracts to guide discovery of alternative antimicrobials with activity against the multidrug-resistant bacterial pathogen <em>Neisseria gonorrhoeae</em>.</div></div><div><h3>Materials and methods</h3><div><em>In vitro</em> antimicrobial activity was analyzed by agar dilution method and time-kill assays, while <em>in vivo</em> activity was evaluated in a mouse infection model. The antimicrobial target was identified by pull-down assays and validated by interaction studies with wild-type and targeted mutant proteins.</div></div><div><h3>Key findings</h3><div>The extract of Chinese <em>Populus spp.</em> propolis (CPP) displayed the most potent antigonococcal activity. Subsequently, galangin was identified as the most active compound in CPP. However, galangin showed no <em>in vivo</em> activity in the mouse infection model. Screening for active structural analogues of galangin resulted in the identification of 2-hydroxychalcone (2-HC), which showed a minimum inhibitory concentration (MIC) of 8–16 μM, and enhanced gonococcal clearance in the infection model. Pull-down experiments identified EF-Tu and butanediol dehydrogenase (Bdh) as putative 2-HC targets. Further binding analysis of 2-HC with recombinant purified proteins showed an equilibrium dissociation constant (<em>K</em>_D) of 1.28 μM for EF-Tu and 5.97 μM for Bdh. Finally, 2-HC binding pockets on EF-Tu and Bdh were identified by molecular docking studies showing that 2-HC interacted with Glu260 of EF-Tu and Ser273 of Bdh, which was validated by mutagenesis studies. For Bdh, we furthermore demonstrated that 2-HC impacted its enzyme activity with and IC₅₀ of 44–64 μM, resulting in perturbed NAD⁺/NADH ratios.</div></div><div><h3>Significance</h3><div>2-HC displays a bimodal antigonococcal mechanism, making it an interesting candidate for further development as antigonococcal therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123994"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182032","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}

{"title":"Selective mitophagy activation and protein aggregate accumulation in MTMR5/SBF1-deficient fibroblasts","authors":"Paola Zanfardino ,&nbsp;Alessandro Amati ,&nbsp;Stefano Doccini ,&nbsp;Francesco Girolamo ,&nbsp;Apollonia Tullo ,&nbsp;Giovanna Longo ,&nbsp;Filippo M. Santorelli ,&nbsp;Vittoria Petruzzella","doi":"10.1016/j.lfs.2025.123995","DOIUrl":"10.1016/j.lfs.2025.123995","url":null,"abstract":"<div><h3>Aims</h3><div>Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a rare autosomal recessive neuropathy caused by biallelic MTMR5/SBF1 variants, which encode a catalytically inactive myotubularin involved in phosphoinositide metabolism and autophagy regulation. This study investigates the impact of MTMR5/SBF1 dysfunction on autophagy and mitophagy in patient-derived fibroblasts and examines the relationship between protein aggregates and autophagic machinery.</div></div><div><h3>Materials and methods</h3><div>Fibroblasts from a CMT4B3 patient with compound heterozygous MTMR5/SBF1 mutations were compared with a healthy control. Autophagic flux was analyzed <em>via</em> LC3B and SQSTM1; mitophagy was assessed through PINK1 and PRKN recruitment and by quantifying mitophagosomes and autolysosomes under mitochondrial stress. Protein aggregates were visualized using Proteostat and tested for colocalisation with autophagic structures.</div></div><div><h3>Key findings</h3><div>CMT4B3 fibroblasts showed normal basal macroautophagy but failed to increase autophagy in response to mitochondrial stress or protein aggregates. Conversely, mitophagy was strongly activated <em>via</em> the PINK1–PRKN pathway.</div></div><div><h3>Significance</h3><div>These results reveal an uncoupling between mitophagy and macroautophagy, indicating that MTMR5/SBF1 mutations modify autophagic selectivity. Our findings provide new mechanistic insights into the pathogenesis of CMT4B3 and highlight the value of patient-derived fibroblasts for studying selective autophagy defects.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123995"},"PeriodicalIF":5.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149812","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}

{"title":"Phocaeicola plebeius oral treatment improve fibrosis by reversing cirrhosis-related hepatic gene dysregulation","authors":"Satya Priya Sharma ,&nbsp;Min-Gi Cha ,&nbsp;Goo-Hyun Kwon ,&nbsp;Seol Hee Song ,&nbsp;Jeong Ha Park ,&nbsp;Min Ju Kim ,&nbsp;Jung A Eom ,&nbsp;Kyeong Jin Lee ,&nbsp;Sang Jun Yoon ,&nbsp;Hyunjoon Park ,&nbsp;Sung-Min Won ,&nbsp;Ki-Kwang Oh ,&nbsp;Young Lim Ham ,&nbsp;Gwang Ho Baik ,&nbsp;Dong Joon Kim ,&nbsp;Ki Tae Suk","doi":"10.1016/j.lfs.2025.123979","DOIUrl":"10.1016/j.lfs.2025.123979","url":null,"abstract":"<div><h3>Background</h3><div><em>Bacteroides</em>-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing <em>Bacteroides</em> species as microbiome-based therapeutic logical to mitigate disease progression.</div></div><div><h3>Materials and methods</h3><div>Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of <em>Bacteroidetes</em> phylum classified microbial species <em>P. plebeius</em> in liver fibrosis pathophysiological pathways.</div></div><div><h3>Results</h3><div><em>Bacteroides</em> presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. <em>P. plebeius</em> significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with <em>P. plebeius</em> significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. <em>P. plebeius</em> decrease the expression of <em>S100a9</em>, <em>CCR1</em>, <em>ADAM8</em>, <em>TREM2</em>, <em>ITGAM</em>, and <em>MYO5A</em> which are primarily responsible for inducing inflammation in liver cirrhosis. <em>P. plebeius</em> downregulated the fibrosis related genes expression including <em>CD51</em>, <em>PLAT</em>, <em>ITGA3</em>, <em>CXCR4</em>, and <em>TGFBR1</em> and gene related to extracellular matrix formation including <em>COL1A1</em>, <em>LTBP2</em>, <em>S100A6</em>, and <em>SMCO2</em>. Additionally, <em>P. plebeius</em> treatment decreased the expression of hepatotoxicity-related genes including <em>LPL</em>, <em>KRT18</em>, <em>ALDOA</em>, and <em>MCM10</em>, and increased the expression of <em>FABP1</em> and <em>RDX</em>. Additionally, <em>P. plebeius</em> normalized the expression of genes connected to two pathophysiological process including <em>TIMP4</em>, <em>TGFB3</em>, <em>S100A8</em>, <em>PLSCR1</em>, <em>MMP8</em>, <em>CXCL4</em>, and <em>BMP</em>.</div></div><div><h3>Conclusions</h3><div>Our study revealed <em>P. plebeius</em> as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123979"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138079","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}

{"title":"Exposure to low-dose CuO nanoparticles improves fear extinction memory and enhance intrinsic excitability in the infralimbic cortex of male mice","authors":"Rahma Ammar ,&nbsp;Laura E. Maglio ,&nbsp;Mariem Naffeti ,&nbsp;María Covadonga Aguado Ballano ,&nbsp;Marta Callejo-Móstoles ,&nbsp;Yassine Chtourou ,&nbsp;Hamadi Fetoui ,&nbsp;David Fernández de Sevilla","doi":"10.1016/j.lfs.2025.123982","DOIUrl":"10.1016/j.lfs.2025.123982","url":null,"abstract":"<div><h3>Aims</h3><div>Nanomaterials have gained considerable attention for diverse medical applications, particularly in neurology. Copper oxide nanoparticles (CuO-NPs) exhibit unique nanoscale properties that enable close interactions with neuronal cells, highlighting their potential as therapeutic agents for modulating synaptic plasticity and improving cognitive function. We aimed to investigate whether low-dose CuO-NPs can enhance fear extinction memory and increase intrinsic excitability in the infralimbic cortex (IL) of male mice.</div></div><div><h3>Materials and methods</h3><div>Adult male mice were subjected to fear conditioning using auditory cues paired with footshocks. Following the administration of a low dose of CuO-NPs, behavioral performance was assessed by measuring freezing responses during extinction. Whole-cell patch-clamp recordings were then performed on IL pyramidal neurons to evaluate intrinsic excitability and AMPA/NMDA ratio. Transmission electron microscopy (TEM) was applied after 2 and 24 h to assess the ability of CuO-NPs to reach the brain.</div></div><div><h3>Key findings</h3><div>We demonstrated via TEM that CuO-NPs efficiently cross the blood-brain barrier within 24 h' post-administration. Using cued fear conditioning, we subsequently found that a single intraperitoneal injection of CuO-NPs enhanced fear extinction memory, as evidenced by a significant reduction in freezing behavior compared to control animals. Patch-clamp analysis confirmed that CuO-NPs increased the excitability of IL pyramidal neurons and induced a sustained reduction in fast, medium, and slow post-spike after hyperpolarizations. Additionally, we demonstrated that CuO-NPs increased <em>N</em>-methyl-<span>d</span>-aspartate receptor-mediated synaptic currents, suggesting an enhanced synaptic plasticity in the infralimbic cortex.</div></div><div><h3>Significance</h3><div>Our findings offer new insights into the potential use of CuO-NPs for modulating fear extinction memory.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123982"},"PeriodicalIF":5.1,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120481","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}

{"title":"The gut microbiota and cardiovascular disease: Exploring the role of microbial dysbiosis and metabolites in pathogenesis and therapeutics","authors":"Amin Mohsenzadeh ,&nbsp;Sahar Pourasgar ,&nbsp;Amirali Mohammadi ,&nbsp;Mahdis Nazari ,&nbsp;Soroush Nematollahi ,&nbsp;Yeganeh Karimi ,&nbsp;Parisa Firoozbakhsh ,&nbsp;Hossein Mohsenzadeh ,&nbsp;Kasra Kamali ,&nbsp;Reza Elahi","doi":"10.1016/j.lfs.2025.123981","DOIUrl":"10.1016/j.lfs.2025.123981","url":null,"abstract":"<div><div>The gut microbiota, a dynamic ecosystem of microorganisms inhabiting the human body, plays a pivotal role in modulating host physiology and immune function, with intense implications for the cardiovascular system. Cardiovascular diseases (CVDs) stand out as the leading cause of mortality worldwide. Gut microbiome dysbiosis is implicated in diverse CVDs, such as hypertension, atherosclerosis, coronary artery disease, heart failure, and myocardial infarction, through mechanisms mediated by microbial-derived metabolites. Key compounds include trimethylamine N-oxide (TMAO) (linked to plaque instability), short-chain fatty acids (SCFAs) (which regulate blood pressure and endothelial function), phenylacetylglutamine (PAGln) (a promoter of thrombotic pathways), and bile acids (influencing lipid metabolism). These metabolites serve as both biomarkers of CVD risk and therapeutic targets. Emerging strategies to modulate the gut microbiota, such as precision probiotics, dietary interventions (e.g., fiber-rich or polyphenol-heavy diets), and pharmacologic inhibitors of microbial enzymes (e.g., TMA lyase blockers), highlight the potential for microbiome-directed therapies. However, challenges remain in elucidating causal microbial pathways, standardizing interventions across diverse populations, and translating preclinical findings into clinical practice. In this mechanistic and translational review, we synthesize current evidence on the bidirectional relationship between gut microbial dysbiosis and CVDs. We explore how modifiable factors, including diet, pharmacotherapy, and early-life microbial colonization, reshape gut communities, driving systemic inflammation, metabolic dysfunction, and vascular pathology. Future research must prioritize longitudinal human studies, multi-omics integration, and randomized trials to harness the gut microbiota's full potential in CVD prevention and personalized treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123981"},"PeriodicalIF":5.1,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131262","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}

{"title":"Effects of apelin on age-associated neovascularization impairment in peripheral artery disease","authors":"Junyu Chen ,&nbsp;Minghong Chen ,&nbsp;Yu Liu ,&nbsp;Xuerui Wang ,&nbsp;Meilian Yao ,&nbsp;Jing Chen ,&nbsp;Jian Zhang ,&nbsp;Qunyong Peng","doi":"10.1016/j.lfs.2025.123980","DOIUrl":"10.1016/j.lfs.2025.123980","url":null,"abstract":"<div><h3>Aims</h3><div>Peripheral artery disease (PAD) is a prevalent vascular condition in the elderly. Aging induces senescence and dysfunction of endothelial cells (ECs), which contributes to impaired neovascularization. This study aims to investigate the therapeutic potential of apelin in restoring neovascularization in older patients with PAD.</div></div><div><h3>Materials and methods</h3><div>We measured plasma apelin levels of young and elderly patients with PAD, as well as in mice following hindlimb ischemia (HLI). Aged mice were treated with apelin or vehicle. Blood flow recovery was monitored using Laser Doppler imaging. To evaluate neovascularization, we performed micro-CT-based vascular angiography, whole-mount, and immunofluorescence staining. In addition, the effects of apelin on ECs were assessed by measuring reactive oxygen species, senescence-associated β-galactosidase staining, and performing a series of functional assays.</div></div><div><h3>Key findings</h3><div>Here, we report for the first time that plasma apelin levels are significantly reduced in older PAD patients and are closely associated with relevant clinical parameters. A similar reduction was also observed in mice following HLI. In aged mice with HLI, apelin treatment markedly enhanced blood flow recovery. Further analysis demonstrated that apelin promotes neovascularization after ischemia. Both <em>in vivo</em> and <em>in vitro</em> experiments confirmed that apelin facilitates neovascularization by improving endothelial function and mitigating ECs senescence <em>via</em> activation of APJ.</div></div><div><h3>Significance</h3><div>This study integrates clinical observations with experimental evidence, highlighting the therapeutic potential of apelin in promoting neovascularization and enhancing its translational relevance for the treatment of PAD in the elderly.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123980"},"PeriodicalIF":5.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109768","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}

{"title":"Obesity-aggravated erythrocyte injury in ischaemia-reperfusion: Interlinked oxidative stress, metabolic reprogramming, and cytoskeletal destabilisation","authors":"Xiaochen Wang ,&nbsp;Rui Li ,&nbsp;Yuanbing You ,&nbsp;Yidi Gao ,&nbsp;Tiantian Wang ,&nbsp;Jingkang Li ,&nbsp;Qiong Zhang","doi":"10.1016/j.lfs.2025.123975","DOIUrl":"10.1016/j.lfs.2025.123975","url":null,"abstract":"<div><div>Anaemia in obese patients who underwent major vascular surgery is closely associated with ischaemia-reperfusion injury (IRI)-driven erythrocyte damage and haemolysis. However, the obesity-specific mechanisms remain unknown. We investigated the interplay among oxidative stress, metabolic reprogramming, and cytoskeletal destabilisation in red blood cells (RBCs) during aortic IRI under obese conditions. Using a high-fat diet-induced obese mouse model subjected to abdominal aortic clamping–reperfusion, we systematically dissected the hierarchical mechanisms linking obesity to erythrocyte vulnerability during IRI. The key findings were<strong>—</strong>oxidative amplification<strong>—</strong>obese mice exhibited a pronounced intraerythrocytic reactive oxygen species surge post-IRI, accompanied by a compensatory upregulation of antioxidant enzymes (catalase and glutathione peroxidase). However, persistent accumulation of oxidative stress markers (malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and carbonylated proteins) indicated overwhelming oxidative stress. Metabolic iron dysregulation<strong>—</strong>elevated Fe³⁺ and methaemoglobin levels and NADPH/ATP depletion indicated concurrent iron homeostasis disruption and metabolic crisis, respectively. RBCs glycolytic reprogramming is characterized by imbalanced glycolytic flux with accumulation of intermediates (glucose-6-phosphate [G6P] and fructose-6-phosphate), despite compensatory activation of the pentose phosphate pathway (PPP) and Rapoport-Luebering shunt (RLS). Structural destabilisation: critical cytoskeletal protein expression including expression of Band 3, glycophorin C, α/β-spectrin, and adducin, was significantly downregulated, with tropomodulin 1 and tropomyosin displaying the most prominent reductions, resulting in membrane fragility and haemolysis (elevated levels of haemoglobin, bilirubin, and circulating methaemoglobin). Collectively, we identified an ‘oxidative–metabolic–structural collapse’ axis that mediates obesity-aggravated erythrocyte injury during IRI, providing a mechanistic foundation for developing perioperative erythrocyte-protective strategies in metabolic syndrome with potential to improve cardiovascular surgery outcomes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123975"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103035","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}