Life sciences最新文献

{"title":"Risk stratification using inflammatory and metabolic biomarkers: A multi-cohort predictive study of mortality in atherosclerotic cardiovascular disease","authors":"Xiao Li ,&nbsp;Qingyue Zeng ,&nbsp;Xiaoyu Zhang ,&nbsp;Shuangqiu Wang ,&nbsp;Tong Jiang ,&nbsp;Liangzheng You ,&nbsp;Hongcai Shang","doi":"10.1016/j.lfs.2025.124182","DOIUrl":"10.1016/j.lfs.2025.124182","url":null,"abstract":"<div><h3>Background</h3><div>The pathological process of atherosclerotic cardiovascular disease (ASCVD) involves complex interactions between metabolic dysregulation and inflammatory responses. The stress hyperglycemia ratio (SHR) and neutrophil-to-lymphocyte ratio (NLR), as biomarkers reflecting metabolic stress and systemic inflammation respectively, have demonstrated significant value in ASCVD prognosis assessment. This study aims to investigate the predictive role of combined SHR and NLR indicators for all-cause mortality in ASCVD patients and their clinical applicability.</div></div><div><h3>Methods</h3><div>ASCVD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and National Health and Nutrition Examination Survey (NHANES) databases, stratified by SHR/NLR tertiles. Multivariable Cox regression, restricted cubic splines, time-dependent ROC, and machine learning models assessed mortality associations.</div></div><div><h3>Results</h3><div>Among 6159 patients, the highest SHR tertile showed increased mortality (NHANES: HR = 1.20, 95 % CI 1.08–1.34; MIMIC-IV: HR = 2.27, 95 % CI 1.44–3.57). The highest NLR tertile showed elevated risk (NHANES: HR = 1.56, 95 % CI 1.39–1.74; MIMIC-IV: HR = 1.61, 95 % CI 1.03–2.52). The combined high SHR/NLR group exhibited the most pronounced risk (NHANES: HR = 1.54, 95 % CI 1.35–1.77; MIMIC-IV: HR = 2.90, 95 % CI 1.70–4.93), with significantly improved predictive accuracy.</div></div><div><h3>Conclusion</h3><div>The combined SHR-NLR assessment effectively quantifies combined metabolic-inflammatory injury and provides superior prognostic stratification for ASCVD patients compared to individual biomarker evaluation. These findings highlight the clinical potential of this dual-biomarker approach for enhancing risk prediction, though further prospective validation is warranted to establish its predictive utility across various patient populations.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124182"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912172","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":"Ameliorating effect and mechanism of p-coumaric acid liposome on cognitive dysfunction and mitochondrial damage under intermittent hypoxia","authors":"Yan-Zi Liang ,&nbsp;Meng-Zhen Jiang ,&nbsp;Xue-Ting Xu ,&nbsp;Ting Zhu ,&nbsp;Hui Guo ,&nbsp;Li Ding ,&nbsp;Hao Zhong ,&nbsp;Jian Bao ,&nbsp;Li-Qiang Qin ,&nbsp;Yun-Hong Li","doi":"10.1016/j.lfs.2026.124197","DOIUrl":"10.1016/j.lfs.2026.124197","url":null,"abstract":"<div><h3>Aims</h3><div>Alzheimer's disease (AD) has become a global public health problem. Mitochondrial dysfunction contributes to AD pathogenesis, and adequate oxygen supply is essential to maintain mitochondrial homeostasis. <em>P</em>-coumaric Acid (CA) is a polyphenol with anti-hypoxia and anti-AD properties. In this study, CA was formulated into a biomimetic liposome (CA-Lip) to enhance its therapeutic efficacy, and the underlying mechanisms were studied.</div></div><div><h3>Materials and methods</h3><div>APP/PS1 mice were divided into four groups: AD group, hypoxia treatment group (AD-HY group), hypoxia + CA treatment group (CA group), hypoxia + CA-Lip treatment group (CA-Lip group). Age-matched wild-type littermates were used as controls. Mice in the hypoxia treatment groups were exposed to a hypoxia chamber for 6 h daily for 8 weeks. Cognitive performance and mitochondrial function were subsequently evaluated to determine the ameliorating effects and mechanisms of CA-Lip.</div></div><div><h3>Results</h3><div>Cognitive impairment and mitochondrial dysfunction were more pronounced in the AD-HY group than in the AD group. CA-Lip produced greater neuroprotective effects than CA. Mechanistic analyses showed that CA-Lip reduced amyloid-β (Aβ) accumulation, enhanced mitochondrial biogenesis (upregulation of PGC-1α expression), maintained mitochondrial dynamics (upregulation of MFN2 expression, and downregulation of DRP1 expression), inhibited excessive mitophagy (downregulation of PINK1 and Parkin expression), enhanced cell autophagy (upregulation of ATG7 and LC3B expression and downregulation of mTOR and P62 expression), and reduced neuronal apoptosis.</div></div><div><h3>Conclusions</h3><div>CA-Lip effectively ameliorates hypoxic cognitive impairment by reducing Aβ generation and improving mitochondrial function.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124197"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927799","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":"Mitochondrial function of peripheral lymphocytes: role on multiple sclerosis clinical subtypes","authors":"Adela González-Jiménez ,&nbsp;Paloma de Heras-Pino ,&nbsp;Alba Moreno-Jerez ,&nbsp;Estela Mena-Plaza ,&nbsp;Yolanda Aladro ,&nbsp;Belén Pilo ,&nbsp;Celia Oreja-Guevara ,&nbsp;Irene Gómez-Estévez ,&nbsp;Andrea R. López-Pastor ,&nbsp;Irene Gómez-Delgado ,&nbsp;Elena Urcelay","doi":"10.1016/j.lfs.2026.124196","DOIUrl":"10.1016/j.lfs.2026.124196","url":null,"abstract":"<div><h3>Aims</h3><div>Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of unknown etiology, resulting in unmet therapeutic needs. Symptoms heterogeneity and incomplete mechanistic understanding hinder effective patient stratification. We aimed to evaluate the integrated peripheral immune response in established MS clinical subtypes, focusing on differences in mitochondrial function that might validate this stratification and further clarify MS etiology.</div></div><div><h3>Materials and methods</h3><div>Mitochondrial activity of peripheral blood mononuclear cells (PBMCs) upon PHA-stimulation was analysed in MS patients (58 relapsing-remitting (RRMS), 21 secondary progressive (SPMS), and 35 primary progressive (PPMS)) and 35 healthy controls (HC).</div></div><div><h3>Key findings</h3><div>In unstimulated conditions, MS patients presented higher mitochondrial ROS (reactive oxygen species) and decreased coupling than HC. Compared with other progressive MS (PMS) subtypes, PBMCs from RRMS presented significantly higher early/late activation and proliferation after PHA stimulation (<em>P</em> = 0.013/<em>P</em> = 0.002, and <em>P</em> = 0.04, respectively), with increased mitochondrial depolarization (<em>P</em> = 0.017). Compared to HC, PHA-stimulated PBMCs from PMS exhibited marked decreases in basal (<em>P</em> = 0.017), maximal, and ATP-linked respiration, increased coupling (<em>P</em> = 0.009), and lower spare respiratory and glycolytic capacities (basal: <em>P</em> = 0.015, maximal: <em>P</em> = 0.064), with parallel decreased GLUT1 expression (<em>P</em> = 0.025). These changes appeared independent of some treatments.</div></div><div><h3>Significance</h3><div>Upon PHA-stimulation, PMS patients displayed decreased basal, maximal, ATP-linked respiration, and reduced spare respiratory and glycolytic capacities, compared to RRMS and HC, mirroring opposed trends in unstimulated conditions. These findings suggest a severity gradient across MS clinical forms, supporting a disease continuum rather than strictly defined subtypes. The central role of unresolved mitochondrial dysfunction in MS warrants further investigation and may guide novel therapeutic strategies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124196"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918064","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":"Early-life sex hormone deficiency promotes beneficial remodeling in white adipose tissue and whole-body metabolism","authors":"Ignacio Miguel ,&nbsp;Ana Alzamendi ,&nbsp;Alejandro Ezequiel Harnichar ,&nbsp;Alejandra Paula Giordano ,&nbsp;Carolina Carla Garraza ,&nbsp;Eduardo Julio Spinedi ,&nbsp;Andrés Giovambattista","doi":"10.1016/j.lfs.2025.124184","DOIUrl":"10.1016/j.lfs.2025.124184","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates the impact of female sex hormone deficiency (FSHD) on white adipose tissue (WAT) development, focusing on two distinct depots: retroperitoneal adipose tissue (RPAT) and inguinal adipose tissue (IAT).</div></div><div><h3>Materials and methods</h3><div>Prepubertal ovariectomy was performed, and animals were pair-fed (FSHD-PF) to account for hyperphagia.</div></div><div><h3>Key findings</h3><div>FSHD-PF animals exhibited reduced plasma triglyceride and insulin levels, with improved glucose handling. A redistribution of adipose tissue was observed, with increased IAT mass and decreased RPAT mass, accompanied by a reduction in adipocyte size in RPAT. Expression markers of inflammation, such as <em>ob</em> and <em>tnf-α</em>, were significantly decreased in RPAT of FSHD-PF, suggesting a potential reduction in the inflammatory state. Likewise, we found that prepubertal ovariectomy also modulated adipocyte precursor cells (APCs), leading to increased <em>cd34</em> expression in both depots, indicative of greater competency. However, RPAT showed elevated <em>pparγ-2</em> levels, while IAT exhibited increased <em>wnt10b</em>, suggesting a depot-specific regulation. Notably, IAT-derived APCs from FSHD-PF animals display enhanced differentiation capacity <em>in vitro</em>. Cold exposure further modulated WAT browning, with a notable increase in UCP-1 protein expression although observed in IAT from FSHD-PF rats only.</div></div><div><h3>Significance</h3><div>This study is the first to examine FSHD in the context of WAT development, identifying early-life ovarian hormone loss as a critical and previously underexplored determinant of metabolic regulation. Accordingly, the consequences of early FSHD, together with its association with non-shivering thermogenesis, emerge as promising areas for further investigation with potential therapeutic relevance.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124184"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906360","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":"O-GlcNAcylation stabilizes c-MYC to upregulate xCT and inhibit ferroptosis in ovarian cancer","authors":"Ying Tang ,&nbsp;Yaru Zhang ,&nbsp;Xinmei Chen ,&nbsp;Xiaotong Li ,&nbsp;Jingyuan Pei ,&nbsp;Ao Wang ,&nbsp;Zhengqing Luo ,&nbsp;Hongshuo Zhang ,&nbsp;Tonghui Ma ,&nbsp;Jianhui Fan ,&nbsp;Ying Kong","doi":"10.1016/j.lfs.2025.124172","DOIUrl":"10.1016/j.lfs.2025.124172","url":null,"abstract":"<div><h3>Aims</h3><div>Ovarian cancer (OV) is one of the most prevalent and life-threatening malignancies among women worldwide. Resistance to conventional therapies poses a major challenge in OV treatment. Ferroptosis, a type of programmed cell death driven by iron accumulation and marked by lipid peroxidation, has garnered significant attention in cancer research. The regulation of ferroptosis involves intricate epigenetic, transcriptional, and post-translational modification (PTM) processes. <em>O-</em>GlcNAcylation, a reversible PTM occurring on serine/threonine hydroxyl groups of proteins, has been connected with the regulation of apoptosis, autophagy, and necroptosis. However, its role in ferroptosis is still poorly understood.</div></div><div><h3>Materials and methods</h3><div><em>O</em>-GlcNAcylation levels and ferroptosis-associated markers were compared between normal and OV tissues. OV cells were subjected to ferroptosis induction using Erastin or RSL3, while <em>O</em>-GlcNAcylation was modulated via the OGT inhibitor OSMI-1 or the OGA inhibitor Thiamet-G. Subsequent analyses were performed to assess ferroptotic phenotypes and the c-MYC/xCT/GSH/GPX4 signaling pathway. In vitro findings were validated using a nude mouse xenograft model.</div></div><div><h3>Key findings</h3><div>In this study, we observed elevated <em>O</em>-GlcNAcylation, higher protein levels of xCT, GPX4, and FTH1, as well as increased antioxidant capacity in ovarian cancer tissues compared with normal ovarian tissues. Modulating <em>O</em>-GlcNAcylation levels in OV cells revealed that its downregulation enhanced ferroptosis, whereas upregulation inhibited it. Further investigation revealed that c-MYC protein levels were regulated by <em>O</em>-GlcNAcylation. The <em>O</em>-GlcNAcylation-mediated stabilization of c-MYC led to increased xCT expression, thereby enhancing the xCT/GSH/GPX4 antioxidant axis and suppressing ferroptosis in OV.</div></div><div><h3>Significance</h3><div>Our research may provide intervention strategies for the treatment of OV.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124172"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850305","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 emerging role of decorin in pancreatic islet biology: From development to degeneration","authors":"Huanjing Bi ,&nbsp;Ruiyang Ma ,&nbsp;Zuhan Chen ,&nbsp;Yang Li ,&nbsp;Xiaoming Ding","doi":"10.1016/j.lfs.2025.124185","DOIUrl":"10.1016/j.lfs.2025.124185","url":null,"abstract":"<div><div>Decorin, a small leucine-rich proteoglycan, has emerged as a multifunctional signaling molecule with critical implications for pancreatic islet biology beyond its canonical role in extracellular matrix organization. Despite extensive characterization of decorin's functions in matrix architecture and growth factor sequestration across various tissues, its specific contributions to pancreatic islet development and homeostasis remain insufficiently explored. Current evidence demonstrates decorin's molecular structure and post-translational modifications enable modulation of signaling pathways through pan-receptor tyrosine kinase inhibition and transforming growth factor-beta sequestration, with regulatory activities that vary substantially across distinct cellular and pathological environments. Within the pancreatic islet microenvironment, decorin influences pancreatic islet morphogenesis and beta-cell differentiation through modulation of local matrix composition and growth factor bioavailability, while conferring protection against diabetic complications through anti-fibrotic properties that mitigate peri-islet extracellular matrix remodeling observed in progressive islet dysfunction. By synthesizing findings from developmental biology, matrix biochemistry, and diabetes research, we address this critical knowledge gap and position decorin as an underrecognized regulator of pancreatic islet biology whose multifaceted mechanisms warrant investigation to reveal therapeutic strategies for preserving beta-cell function and preventing diabetes-associated fibrotic pathology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124185"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896694","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":"UAMC-3203 attenuates aortic dissection by targeting ferroptosis-mediated vascular smooth muscle cell loss","authors":"Wenjie Fu ,&nbsp;Xinyu Li ,&nbsp;Linlong Guo ,&nbsp;Yalu Huang ,&nbsp;Luyao Hong ,&nbsp;Lin Zhong ,&nbsp;Ziru Li ,&nbsp;Binxing Lu ,&nbsp;Yanqing Fang ,&nbsp;Zhihuang Qiu ,&nbsp;Liangwan Chen ,&nbsp;Yumei Li","doi":"10.1016/j.lfs.2025.124158","DOIUrl":"10.1016/j.lfs.2025.124158","url":null,"abstract":"<div><div>Aortic dissection (AD), which is a lethal cardiovascular emergency, lacks effective pharmacological interventions. The pathogenesis of AD is complex, and the loss of vascular smooth muscle cells (SMCs) is considered to be a key pathological feature. Regulated cell death (RCD) is an important pathway leading to SMC loss. Ferroptosis, which is a novel type of RCD, is characterized by an abnormal accumulation of lipid peroxides. However, the specific mechanism of ferroptosis in the occurrence and development of AD has not been fully elucidated. This study examined ferroptosis in AD progression and assessed anti-ferroptosis treatment. Human AD tissues were analyzed for ferroptosis markers. An AD mouse model was induced using β-aminopropionitrile (BAPN) and angiotensin II (Ang II), followed by UAMC-3203 administration to inhibit ferroptosis. Human aortic vascular SMCs (HAVSMCs) were used to investigate UAMC-3203's mechanism. We demonstrated that ferroptosis was involved in the development of human AD through the upregulation of <em>HMOX1</em> and <em>4-HNE</em>, as well as the downregulation of <em>GPX4</em> and <em>FSP1</em>. The involvement of ferroptosis in the entire AD process in AD mice was confirmed by the stage-specific upregulation of <em>Hmox1</em> and downregulation of <em>Gpx4</em>, as well as by time-specific substitution. The inhibition of ferroptosis expression with UAMC-3203 reduced AD morbidity and mortality, maintained aortic structural integrity, caused the alignment of elastic fibers, and reduced collagen deposition. Mechanistically, UAMC-3203 attenuated SMC death and loss by inhibiting lipid peroxidation. Our result provides new information on the role of ferroptosis in AD progression from an antiferroptosis perspective.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124158"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804875","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":"Retraction notice to “A novel approach to bladder dysfunction induced by bladder outlet obstruction: Low-intensity extracorporeal shock wave therapy promotes bladder regeneration” [Life Sci. 378 (2025) 123799]","authors":"Sheng-Tang Wu ,&nbsp;Tai-Jui Juan ,&nbsp;Jian-He Lu ,&nbsp;Kuang-Shun Chueh ,&nbsp;Jing-Wen Mao ,&nbsp;Cheng-Yu Long ,&nbsp;Shu-Mien Chuang ,&nbsp;Mei-Chen Shen ,&nbsp;Ting-Wei Sun ,&nbsp;Chiang-Ting Wang ,&nbsp;Yung-Shun Juan","doi":"10.1016/j.lfs.2025.124178","DOIUrl":"10.1016/j.lfs.2025.124178","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124178"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878616","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":"Role and mechanism of ASGR1 in acute liver injury","authors":"Lingli Huang ,&nbsp;Yanshi Wang ,&nbsp;Dai Li ,&nbsp;Ge Gao ,&nbsp;Hui Wu ,&nbsp;Youjie Zeng ,&nbsp;Siyi Zhang ,&nbsp;Ziying Chen ,&nbsp;Ren Guo ,&nbsp;Ruifang Chen","doi":"10.1016/j.lfs.2025.124157","DOIUrl":"10.1016/j.lfs.2025.124157","url":null,"abstract":"<div><h3>Aims</h3><div>ASGR1 is a hepatocyte surface glycoprotein receptor that plays a crucial role in maintaining liver homeostasis. This study investigates its role in acute liver injury (ALI) and whether it is associated with the regulation of PANoptosis-like pathway.</div></div><div><h3>Materials and methods</h3><div>An LPS/D-Gal-induced ALI model was established using ASGR1 knockout mice. Liver function, inflammation, oxidative stress, mitochondrial function, and PANoptosis-like markers were assessed. In vitro studies on primary hepatocytes examined the effects of ASGR1 knockout or overexpression on ALI, with the ROS inhibitor NAC and NOXs inhibitor DPI used to explore underlying mechanisms.</div></div><div><h3>Key findings</h3><div>In the ALI model, ASGR1 expression was decreased, and ASGR1^−/− mice showed lower survival, more severe liver injury, and higher inflammatory cytokine levels. Electron microscopy revealed pronounced cell death–associated morphological changes in ASGR1^−/− hepatocytes under ALI. Using multiple cell death inhibitors, we confirmed that apoptosis and necroptosis were the predominant death modalities, consistent with increased BAX/BCL-2 ratio, cleaved caspase-8, p-RIPK1, p-RIPK3, and p-MLKL. Proteomic analysis revealed that the differentially expressed proteins were predominantly enriched in pathways related to oxidative stress and mitochondrial function. ASGR1 deficiency in ALI led to elevated ROS levels and a marked reduction in mitochondrial membrane potential, both of which were reversed by NOXs inhibition. Importantly, scavenging ROS and inhibiting NOXs substantially mitigated the activation of the PANoptosis-like pathway induced by ASGR1 deficiency.</div></div><div><h3>Significance</h3><div>ASGR1 downregulation aggravates ALI via the NOXs–ROS–PANoptosis-like axis, underscoring the pivotal role of ASGR1 in ALI progression.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124157"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827210","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":"Advances in AI for predicting pharmacological properties of natural medicines","authors":"Tianyu Xu ,&nbsp;Yuemiao Xu ,&nbsp;Jinger Zhang ,&nbsp;Yuchen Zhou ,&nbsp;Huiying Feng ,&nbsp;Aiqin Zhang ,&nbsp;Yuhua Zhang","doi":"10.1016/j.lfs.2025.124180","DOIUrl":"10.1016/j.lfs.2025.124180","url":null,"abstract":"<div><div>Artificial intelligence (AI), which includes machine learning (ML) and deep learning (DL), has become an important tool in drug development. An increasing number of studies have discovered pharmacologically active compounds in natural products, and AI's high-throughput capabilities have accelerated the drug discovery process. In the development of natural medicines, AI can use existing datasets and experimental data to screen for lead compounds with potential activity and predict disease-associated drug targets. Furthermore, using AI to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of lead compounds early in the drug discovery process can save time and money. This review introduces AI applications for predicting the pharmacological properties of natural drugs by outlining model construction principles and recent advances, summarizing key aspects such as feature selection and evaluation metrics, and discussing natural drug development challenges and opportunities.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"387 ","pages":"Article 124180"},"PeriodicalIF":5.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847719","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}