Life sciences最新文献

{"title":"The role and mechanisms of RNA-binding proteins in the development of ovarian aging and related diseases","authors":"Wenjia Luo ,&nbsp;Chunxia Huang ,&nbsp;Ke Sun ,&nbsp;Kangping Yang ,&nbsp;Jiaqiang Wu ,&nbsp;Liang Yang","doi":"10.1016/j.lfs.2025.123792","DOIUrl":"10.1016/j.lfs.2025.123792","url":null,"abstract":"<div><div>Ovarian aging is a key factor influencing female fertility and overall health. RNA-binding proteins (RBPs) regulate mRNA stability and translation, playing a significant role in maintaining ovarian function. This review discusses RBPs' involvement in oocyte development, folliculogenesis, and ovarian homeostasis. Additionally, we explore their roles in ovarian aging-related diseases and potential strategies for mitigating ovarian decline by targeting RBP activity. This review highlights RBPs' molecular mechanisms and potential applications for understanding and treating ovarian aging.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123792"},"PeriodicalIF":5.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212988","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":"BDNF/TrkB signaling pathway and WDR neurons: Core factors inducing central sensitization of neuropathic pain","authors":"Yebei Zhong ,&nbsp;Cheng Huang","doi":"10.1016/j.lfs.2025.123796","DOIUrl":"10.1016/j.lfs.2025.123796","url":null,"abstract":"<div><div>Neuropathic pain is a complex pain syndrome resulting from damage or dis-ease affecting the somatosensory nervous system. Currently, there are no effective treatment options available, which has drawn considerable attention from researchers due to its high prevalence. The mechanisms underlying neuropathic pain are multifaceted, involving structural and functional alterations in central nervous system (CNS), pain signals transduction, and neuroinflammation, with central sensitization recognized as an important mechanism. Central sensitization is characterized by increased neuronal excitability and synaptic plasticity. Brain-derived neurotrophic factor (BDNF) plays a pivotal role in central sensitization induced by nerve injury through its binding to the tropomyosin receptor kinase B (TrkB) receptor. The activation of BDNF/TrkB signaling pathway modulates neuronal synaptic plasticity and enhances the transmission of pain signals. Additionally, the spinal dorsal horn (SDH) wide dynamic range (WDR) neurons act as integrative centers for pain signals, receiving inputs from peripheral nociceptive stimuli and exhibiting heightened excitability in neuropathic pain. Hyperexcited WDR neurons not only respond to central sensitization but also are further intensified by BDNF/TrkB signaling pathway, ultimately amplifying pain perception. This review intends to systematically summarize the interactions between central sensitization, BDNF/TrkB signaling, and WDR neurons, illustrating their potential relationships in neuropathic pain and identifying possible intervention targets, thereby offering new insights and strategies for neuropathic pain relief.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123796"},"PeriodicalIF":5.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212989","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":"Absence of Rab39b-induced macroautophagy impairment increases neurotoxic α-synuclein and causes degeneration of substantia nigra dopaminergic neurons in mouse model of X-linked Parkinson's disease","authors":"Ching-Chi Chiu ,&nbsp;Yi-Hsin Weng ,&nbsp;Tu-Hsueh Yeh ,&nbsp;Wan-Shia Chen ,&nbsp;Shu-Yu Liu ,&nbsp;Tai-Ju Chiu ,&nbsp;Allen Hon-Lun Li ,&nbsp;Hung-Li Wang","doi":"10.1016/j.lfs.2025.123789","DOIUrl":"10.1016/j.lfs.2025.123789","url":null,"abstract":"<div><div>Deletion or mutation of RAB39B gene causes RAB39B deficiency in male patients and resulting X-linked Parkinson's disease (PD). Male Rab39b knockout (Rab39b^-/Y) mouse, which simulates PD RAB39B genetic mutation-induced absence of functional RAB39B, was prepared to study pathomechanisms of RAB39B deficiency-evoked neurodegeneration of substantia nigra (SN) dopaminergic cells. Rab39b^-/Y mice manifested PD motor impairment, degeneration of SN dopaminergic neurons and presence of SN Lewy bodies. Rab39b insufficiency caused macroautophagy impairment via reducing Atg3, Atg5, Atg7, Atg12 and Atg16L1 in SN. Rab39b deficiency-induced macroautophagy impairment upregulated α-synuclein within SN dopaminergic neurons and α-synuclein oligomers in SN. Macroautophagy activator rapamycin reversed macroautophagy dysfunction or upregulation of SN α-synuclein and ameliorated motor deficits and demise of SN dopaminergic neurons in Rab39b^-/Y mice. Rab39b paucity-promoted upregulation of ER α-synuclein activated ER stress-triggered apoptotic signaling in SN. Rab39b insufficiency increased SN mitochondrial α-synuclein and produced mitochondrial defect and oxidative stress. Rab39b deficiency-induced ER stress apoptotic signaling, mitochondrial impairment and oxidative damage activated mitochondrial pro-apoptotic pathway in SN. Rab39b deficiency-induced upregulation of α-synuclein oligomers induced excitation of SN microglia and NLRP3 inflammasome and elevation of IL-1β, IL-18 or TNF-α. Rab39b paucity-induced upregulation of pro-inflammatory cytokines activated MKK4-JNK -c-Jun/ATF-2 pro-apoptotic cascade and RIPK1-RIPK3-MLKL necroptotic pathway in SN. Our results suggest that RAB39B deficiency causes demise of SN dopaminergic neurons and X-linked PD by impairing macroautophagy and upregulating neurotoxic α-synuclein, which stimulates ER stress and mitochondrial apoptotic cascades and activates microglia and NLRP3 inflammasome. Our data also suggest that rapamycin possesses therapeutic effects on RAB39B mutation-induced X-linked PD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123789"},"PeriodicalIF":5.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212987","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":"STC1 promotes paclitaxel resistance in oral squamous cell carcinoma by inhibiting oxidative stress via activating the JAK/STAT signaling pathway","authors":"Xinghan Wu ,&nbsp;Hao Liu ,&nbsp;Mingfeng Li ,&nbsp;Chuanni Feng ,&nbsp;Min Liu ,&nbsp;Yanfeng Xu ,&nbsp;Yalan Lu ,&nbsp;Yanju Gong ,&nbsp;Xiaomeng Li ,&nbsp;Fan Ye ,&nbsp;Lin Jiang ,&nbsp;Yanhong Li ,&nbsp;Binbin Li ,&nbsp;Chuan Qin","doi":"10.1016/j.lfs.2025.123787","DOIUrl":"10.1016/j.lfs.2025.123787","url":null,"abstract":"<div><h3>Aims</h3><div>Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, with chemoresistance is the greatest challenge in chemotherapeutic treatment. Stanniocalcin 1 (STC1) is correlated with tumor malignancy and chemoresistance in various cancers, but its role in OSCC paclitaxel (PTX) resistance remains elusive. This study aimed to clarify STC1's impact on OSCC PTX resistance and elucidate its underlying mechanism.</div></div><div><h3>Materials and methods</h3><div>The PTX-resistant OSCC cell line CAL-27/PTX was established by stepwise exposure to increasing PTX concentrations. Transcriptomic sequencing, CCK-8 assays, western blotting, RT-qPCR, lentiviral-mediated silencing or overexpression, reactive oxygen species (ROS) detection, and ELISA were used to assess STC1 expression and function. In vivo validation was conducted using both cell line-derived (CDX) and patient-derived xenograft (PDX) models.</div></div><div><h3>Key findings</h3><div>The expression of STC1 was significantly increased in CAL-27/PTX cells and linked to cancer stem cell-like characteristics and epithelial-mesenchymal transition. Knockdown of STC1 expression suppresses tumor development. Mechanistically, STC1 activated the JAK/STAT signaling pathway, which mediated the upregulation of antioxidant genes (GPX4, FTH1, and SLC7A11) to attenuate PTX-induced oxidative stress. Additionally, STC1 promoted intercellular transfer of PTX resistance via a paracrine mechanism. In vivo, high STC1 expression mediated PTX resistance in both CDX and PDX tumor models.</div></div><div><h3>Significance</h3><div>This study identifies the STC1-STAT3-SLC7A11 axis as a key regulator of resistance to oxidative stress in OSCC, highlighting STC1 as a promising therapeutic target to overcome chemoresistance and improve outcomes in PTX-based therapies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123787"},"PeriodicalIF":5.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212986","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":"Under pressure: Updated insights into the mechanisms of Leishmania's defense in response to oxidative stress.","authors":"Angélica Paulina Nunes, Yasmin Munhoz Dos Santos-Destro, Ana Carolina Jacob Rodrigues, Mariana Barbosa Detoni, Ellen Mayara de Souza, Giovana Sita Berbert, Byulnim Park, Maria Fernanda Kuriki Pires, Wander Rogério Pavanelli, Maiara Voltarelli Providello","doi":"10.1016/j.lfs.2025.123779","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123779","url":null,"abstract":"<p><p>Leishmaniasis is a disease caused by over 20 species of protozoa of the genus Leishmania, transmitted by the bite of infected phlebotomine sandflies. This parasitic infection has an anthropozoonotic nature, affecting both wild and domestic animals, as well as humans. It may present itself as three main clinical forms: cutaneous, mucocutaneous, or visceral leishmaniasis. The interaction between the parasite and the host's immune system is complex, involving evasion mechanisms primarily through the modulation of oxidative stress. Leishmania lacks several antioxidant enzymes common to mammals; instead, it relies on a few alternative redox systems, such as the trypanothione family which is essential for counteracting reactive oxygen and hydrogen species within phagolysosomes of neutrophils and macrophages. These mechanisms also modulate the composition and pH of the parasitophorous vacuole, preventing the efficient elimination of the amastigote forms from host cells. Additionally, the parasite induces cytoskeletal and metabolic changes in mammalian host cells to promote a favorable microenvironment for its survival. Given these aspects, this review discusses Leishmania's oxidative stress evasion strategies, focusing on both parasite-specific adaptations and their effects on host metabolism and immune response, whether in macrophages, neutrophils, or dendritic cells; as well as the role of oxidative stress in canine visceral leishmaniasis. A deeper understanding of these mechanisms may support the development of novel therapeutic approaches, such as drugs targeting oxidative response modulation and improved vaccination strategies.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123779"},"PeriodicalIF":5.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216257","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":"METTL3-mediated m6A modification of FUNDC1/IP3R2 pathway facilitates cardiac hypertrophy in obesity hypertension","authors":"Yulong Ma ,&nbsp;Da Li ,&nbsp;Xunjie Zhou,&nbsp;Xiaozhe Chen,&nbsp;Chunlei Hou,&nbsp;Yunfeng Li,&nbsp;Yuxiu Zhao,&nbsp;Mingtai Gui,&nbsp;Lei Yao,&nbsp;Jianhua Li,&nbsp;Mingzhu Wang,&nbsp;Deyu Fu,&nbsp;Bo Lu","doi":"10.1016/j.lfs.2025.123780","DOIUrl":"10.1016/j.lfs.2025.123780","url":null,"abstract":"<div><h3>Background</h3><div>FUNDC1-mediated mitochondria-associated endoplasmic reticulum membrane (MAM) Ca²⁺ conduction is crucial in cardiac hypertrophy. N6-methyladenosine (m6A) methylation, a crucial mRNA modification, is implicated in this process. We hypothesise that m6A regulation of FUNDC1-mediated MAM-associated Ca²⁺ overload contributes to obesity hypertension (OBH) cardiac hypertrophy.</div></div><div><h3>Methods</h3><div>We investigated OBH in spontaneously hypertensive rats fed a high-fat diet, with WKY rats as controls. Assessments included blood pressure, cardiac hypertrophy, pyroptosis, protein expression of MAM-related (FUNDC1, IP3R2) and m6A-related gene (METTL3, IGF2BP2). MeRIP assay detected m6A methylation in mRNA. We also examined cardiomyocyte morphology, viability, mitochondrial function (mtROS, SOD, MDA and ATP levels), and expression of pyroptosis-related factors (IL-1β, IL-18, NLRP3, GSDMD-N and Caspase-1/p10) in vitro. Silencing and overexpression of FUNDC1 and METTL3 clarified MAM effects on cardiac hypertrophy. FUNDC1 and IP3R2 interaction was assessed by co-immunoprecipitation.</div></div><div><h3>Results</h3><div>OBH rats exhibited significantly elevated blood pressure, cardiac hypertrophy, MAM dysfunction, elevated FUNDC1, IP3R2 and METTL3 expression, and pyroptosis. Ang II treatment in vitro upregulated FUNDC1, causing mitochondrial dysfunction, inflammation and pyroptosis in cardiomyocytes. FUNDC1 knockdown improved cardiomyocyte morphology and function, reduced mitochondrial Ca²⁺ concentration, enhanced mitochondrial function and attenuated pyroptosis while increasing IP3R2 ubiquitination. Mito Tempo reversed cardiomyocyte hypertrophy, mitochondrial dysfunction, inflammatory response and pyroptosis induced by FUNDC1 overexpression. Additionally silencing METTL3 and IGF2BP2 reduced m6A methylation of FUNDC1, inhibiting its expression.</div></div><div><h3>Conclusion</h3><div>METTL3 regulates FUNDC1 m6A methylation modification via IGF2BP2, thereby affecting FUNDC1 expression. FUNDC1 binding to IP3R2 regulates MAM-associated Ca²⁺ overload, inducing mitochondrial dysfunction and pyroptosis, leading to cardiac hypertrophy in OBH.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123780"},"PeriodicalIF":5.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199524","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":"Diamine oxidase acts as a novel risk factor in abnormal inflammation via mediating “cytosolic ROS-autophagy-IFN-γ” axis in NK cells","authors":"Dongmei He ,&nbsp;Weihong Dai ,&nbsp;Yiqin Cui ,&nbsp;Rui Gao ,&nbsp;Xue Yang ,&nbsp;Wei Li ,&nbsp;Jing Zhou ,&nbsp;Shuangqin Yin ,&nbsp;Tianyin Kuang ,&nbsp;Junyu Zhu ,&nbsp;Li Luo ,&nbsp;Rixing Wang ,&nbsp;Ye Qu ,&nbsp;Caihong Yun ,&nbsp;Lizhu Liu ,&nbsp;Xiaoyan Diao ,&nbsp;Xiaoyuan Ma ,&nbsp;Huaping Liang ,&nbsp;Fangjie Wang","doi":"10.1016/j.lfs.2025.123775","DOIUrl":"10.1016/j.lfs.2025.123775","url":null,"abstract":"<div><h3>Aims</h3><div>Diamine oxidase (DAO), a well-established biomarker for intestinal damage, histamine intolerance or tumorigenesis, has rarely been reported in immune regulation. This study aimed to identify DAO as a critical enhancer of abnormal inflammation by promoting interferon-gamma (IFN-γ) production from natural killer (NK) cells.</div></div><div><h3>Main methods</h3><div>Clinical bioinformatics analyzed <em>aoc1</em> (DAO-coding gene) expression in PBMCs from patients with inflammatory diseases. Murine models (LPS-induced systemic inflammation, sepsis, DSS-induced colitis) using DAO^−/− mice, alongside DAO^−/− NK92 cells and DAO inhibitor DIZE, were employed for phenotypic validation. Cellular profiling, bone marrow chimeras, reciprocal transplantation, RNA-sequence, non-targeted metabolomics, and flow cytometry were utilized to dissect DAO's mechanisms in NK cells.</div></div><div><h3>Key findings</h3><div>DAO deficiency protected mice from inflammatory pathology by suppressing IFN-γ production. NK cells were identified as the primary target cells during the process, with DAO acting intracellularly to promote IFN-γ via a reactive oxygen species (ROS)-autophagy axis. DAO-derived ROS, distinct from mitochondrial or NOX2 sources, enhanced autophagic flux during NK activation, enabling IFN-γ biosynthesis. DAO did not affect NK homeostasis, including maturation, proliferation, or receptor expressions.</div></div><div><h3>Significance</h3><div>DAO is a novel risk factor in inflammatory diseases, driving IFN-γ production through ROS-autophagy signaling in NK cells. Targeting DAO may offer therapeutic strategies for conditions involving dysregulated IFN-γ responses, including sepsis, colitis, and autoimmune disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123775"},"PeriodicalIF":5.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190011","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":"A review of cellular and molecular interactions between endocannabinoids and male fertility: Balancing beneficial and detrimental effects","authors":"Shadi Mohammadpour-Asl ,&nbsp;Ali Parvin ,&nbsp;Naeimeh Akbari-Gharalari ,&nbsp;Negar Asadi ,&nbsp;Araz Pooryai ,&nbsp;Shiva Roshan-Milani","doi":"10.1016/j.lfs.2025.123778","DOIUrl":"10.1016/j.lfs.2025.123778","url":null,"abstract":"<div><div>The endocannabinoid system (ECS) has significant potential to influence male reproductive functions by targeting both the central nervous system and peripheral tissues, thereby promoting testicular homeostasis. Endogenous cannabinoids (eCBs) play an important role in regulating reproductive hormones, spermatogenesis, sperm motility, maturation, and function, all crucial for successful fertilization. However, excessive amounts of eCBs disrupt the function of testicular cells, leading to impaired sperm production, reduced motility and capacitation, premature acrosome response, and enhanced apoptosis. Despite these findings, the cellular and molecular mechanisms underlying the implications of eCBs in male reproduction remain unclear. This review is an attempt to provide an insight into the main mechanisms activated by the cross-talk between the ECS and male (in)fertility. The information presented in this report was obtained through an extensive review of scientific literature from various databases, including Web of Science, PubMed, Elsevier, Scopus, and Google Scholar. The reviewed studies suggest that oxidative stress, inflammation, and apoptosis are among the major modulatory mechanisms through which the ECS may contribute to male (in)fertility. This knowledge may lead to the development of potential clinical applications targeting endocannabinoid signaling to address infertility and enhance reproductive health in men.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123778"},"PeriodicalIF":5.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191959","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":"Macrophage histone lactylation in atherosclerosis progression: mechanisms, predictive models, and therapeutic potential of Ruan Jian Qing Mai formula","authors":"Zhi-qiang Liang ,&nbsp;Wang-sheng Luo ,&nbsp;Chen-chen Tang ,&nbsp;Yi-lang Zhong ,&nbsp;Chen-qin Xu ,&nbsp;Chao Ma ,&nbsp;Cheng-lin Jia ,&nbsp;Tong-kai Cai ,&nbsp;Yong-bing Cao ,&nbsp;Ji Li ,&nbsp;Jian Chen","doi":"10.1016/j.lfs.2025.123777","DOIUrl":"10.1016/j.lfs.2025.123777","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates the role of macrophage histone lactylation—a protein modification—in atherosclerosis progression, particularly in peripheral artery disease (PAD), and evaluates the therapeutic potential of the herbal formula Ruan Jian Qing Mai (RJQM).</div></div><div><h3>Materials and methods</h3><div>Weighted gene co-expression network analysis (WGCNA), functional enrichment, and machine learning were used to explore regulatory mechanisms and develop a predictive model for subclinical atherosclerosis. Experimental validation included ApoE−/− mice treated with RJQM and molecular docking to assess drug-protein interactions.</div></div><div><h3>Key findings</h3><div>Our analysis identified 2853 histone lactylation-related genes, of which 117 were significantly correlated with macrophage infiltration across carotid, femoral, and infrapopliteal arteries. WGCNA revealed a strong correlation (<em>r</em> = 0.93, <em>P</em> = 7e−47) between the turquoise module and macrophage infiltration, indicating the potential regulatory role of histone lactylation in inflammatory processes. Functional enrichment analysis highlighted the involvement of these proteins in immune responses, particularly cytokine signaling, with hub proteins such as PTPN6 and CASP1 being pivotal. Furthermore, we developed a consensus signature using machine learning methodologies that demonstrated robust predictive power (average area under the curve, AUC &gt; 0.817) for subclinical atherosclerosis. Experimental validation in ApoE−/− mice indicated that the RJQM effectively reduced plaque area by 39 % (<em>P</em> &lt; 0.05) and modulated macrophage pyroptosis and inflammation.</div></div><div><h3>Significance</h3><div>This research uncovers novel insights into the regulatory mechanisms of macrophage histone lactylation in atherosclerosis and validates the potential of RJQM as a therapeutic strategy, warranting further exploration of its protein modifications and underlying molecular pathways.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123777"},"PeriodicalIF":5.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178058","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":"Multi-omics analysis of outer membrane vesicles from P. goldsteinii in a psoriasis mouse model","authors":"Anqi Du ,&nbsp;Jiayu Chen ,&nbsp;Zhaoxiang Xie ,&nbsp;Yu Yang ,&nbsp;Chun-Bing Chen ,&nbsp;Chun-Wei Lu ,&nbsp;Chien-Chun Liu ,&nbsp;Maoli Chen ,&nbsp;Wen-Hung Chung ,&nbsp;Chen Lin ,&nbsp;Rongqin Ke ,&nbsp;Chih-Jung Chang","doi":"10.1016/j.lfs.2025.123776","DOIUrl":"10.1016/j.lfs.2025.123776","url":null,"abstract":"<div><h3>Aims</h3><div>Psoriasis is a chronic skin inflammation with no complete cure. <em>Parabacteroides goldsteinii</em> (<em>P. goldsteinii</em>), a probiotic, alleviates inflammation by modulating gut microbiota. Its outer membrane vesicles (PG-OMVs) deliver microbial molecules to influence host-microbiota interactions. However, their role in psoriasis remains unclear. This study explores the effects and mechanisms of PG-OMVs in psoriasis.</div></div><div><h3>Materials and methods</h3><div>PG-OMVs were isolated from <em>P. goldsteinii</em> using high-pressure tangential flow ultrafiltration combined with size exclusion chromatography, and characterized by transmission electron microscopy and nano-flow cytometry. Subsequently, Lipidomic and proteomic analysis was performed to investigate the composition of PG-OMVs. A psoriasis-like mouse model was established using imiquimod to evaluate their therapeutic effects. Furthermore, transcriptomic analysis, in situ sequencing, and 16S rRNA sequencing were applied to skin and fecal samples to explore underlying mechanisms. An in vitro model using LPS-stimulated HaCaT keratinocytes was also employed to assess the cytotoxicity and anti-inflammatory activity of PG-OMVs.</div></div><div><h3>Key findings</h3><div>PG-OMVs have an average diameter of approximately 84.9 nm and a uniformly disc-like morphology. Lipidomic and proteomic revealed diverse lipid species and proteins potentially involved in regulating metabolic dysfunction. In the imiquimod-induced mouse model, PG-OMVs alleviated skin lesions and histopathological changes. Mechanistic studies showed that PG-OMVs modulate mTOR, TNF, and IL-17 pathways, regulate inflammatory and proliferative genes (e.g., AKT1, mTOR, FOS, FOSB), and restore gut microbial balance. In vitro, PG-OMVs significantly suppressed pro-inflammatory cytokines.</div></div><div><h3>Significance</h3><div>This study demonstrates that PG-OMVs ameliorate psoriasis by regulating inflammatory pathways and the gut microbiota, offering a promising therapeutic strategy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123776"},"PeriodicalIF":5.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189888","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}