Life sciences最新文献

{"title":"Human urine-derived stem cells from different donor sources ameliorate diabetic nephropathy in mice by activating autophagy and restoring mitochondrial function of podocyte","authors":"Jie-Zhou ,&nbsp;Ya-Yi Lin ,&nbsp;Wei-Fen Cheng ,&nbsp;Xi-Yan Wang ,&nbsp;Zi-Wei Chen ,&nbsp;Xin-Yi Jiang ,&nbsp;Shao-Bo Li ,&nbsp;Xiang-Cheng Zhang ,&nbsp;Ling-Fei Yan ,&nbsp;Lin-Xie ,&nbsp;Jing-Yuan Li ,&nbsp;Quan-Wen Liu","doi":"10.1016/j.lfs.2025.123831","DOIUrl":"10.1016/j.lfs.2025.123831","url":null,"abstract":"<div><h3>Background</h3><div>Human urine-derived stem cells (hUSCs) are a novel type of mesenchymal stem cells (MSCs) originating from the kidney, with promising potential for personalized therapies. However, it remains unclear whether hUSCs can be successfully isolated from individuals of different ages and disease states-including healthy young individuals, healthy elderly individuals, and patients with diabetic nephropathy (DN), as well as their therapeutic potential and mechanism in DN.</div></div><div><h3>Methods</h3><div>hUSCs were isolated from healthy young men (hUSC-HY), healthy elderly men (hUSC-HE), and male DN patients (hUSC-DN), and their biological characteristics were systematically evaluated. The therapeutic effects of early-passage (P3-P5) hUSC-HY, hUSC-HE, and hUSC-DN were assessed in DN mouse models. <em>In vitro</em>, the effects of conditioned medium (CM) derived from each hUSC group on apoptosis in high glucose (HG)-injured mouse podocytes (MPC5) were assessed. To explore the underlying mechanisms, autophagy activation and mitochondrial function were further analyzed in HG-injured MPC5 cells treated with or without hUSC-CM.</div></div><div><h3>Results</h3><div>Early-passage (P0-P5) hUSC-HY, hUSC-HE, and hUSC-DN exhibited comparable biological characteristics. However, after passage 5, hUSC-HE and hUSC-DN progressively developed senescent phenotypes. Early-passage hUSC-HY, hUSC-HE, and hUSC-DN effectively improved renal function and ameliorated tissue damage in DN mice, primarily by inhibiting HG-induced podocyte apoptosis. <em>In vitro</em>, CM derived from all three hUSCs types (P3–P5) significantly attenuated HG-induced apoptosis in podocytes (MPC5 cells) by the activation of autophagy through suppression of the PI3K/AKT/mTOR and ERK/mTOR signaling pathways. Additionally, hUSCs were shown to deliver functional mitochondria to injured MPC5 cells, thereby restoring mitochondrial function and further contributing to the inhibition of podocyte apoptosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123831"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536202","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":"Comprehensive overview of the complex gut microbiota–miRNA crosstalk in immunocompromised pediatric patients","authors":"Regiane Nogueira Spalanzani ,&nbsp;Thaís Muniz Vasconcelos ,&nbsp;Lorena Bavia ,&nbsp;Luiza Souza Rodrigues ,&nbsp;Dany Mesa ,&nbsp;Aline Simoneti Fonseca ,&nbsp;Luciane Regina Cavalli ,&nbsp;Libera Maria Dalla-Costa","doi":"10.1016/j.lfs.2025.123833","DOIUrl":"10.1016/j.lfs.2025.123833","url":null,"abstract":"<div><div>Immunocompromised pediatric patients, particularly those diagnosed with leukemia, often experience immune suppression due to prolonged use of immunosuppressive medication and chemotherapy. Consequently, these patients are highly vulnerable to infections caused by both pathogenic and non-pathogenic microorganisms. To prevent such infections, antibiotics and antifungals are routinely administered as prophylactic treatments. However, the use of antimicrobials significantly impacts the patient's microbiota, particularly the gut microbiota, which plays a crucial role in immunomodulating the mucosa and maintaining the integrity of the intestinal epithelium. Disruption of these functions may transform the intestinal epithelium into a potential entry point for harmful microorganisms. The regulation of gut homeostasis and the composition of the intestinal microbiota have been linked to different host-derived microRNAs (miRNAs) that regulate gene expression. Intestinal epithelial cells release miRNAs into the lumen, where they modulate the growth of gut microbes and the microbiota's composition. This review summarizes current insights into the relationship between the gut microbiota and intestinal miRNAs, emphasizing their potential as diagnostic and prognostic biomarkers for immunocompromised pediatric patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123833"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560509","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":"Rab26-mediated lysosomal translocation of eEF1A alleviates myocardial hypertrophy and cardiac remodeling","authors":"Yifan Tong ,&nbsp;Yutong Li ,&nbsp;Yaguang Bi ,&nbsp;Yajiao Liu ,&nbsp;Xiaoping Peng ,&nbsp;Binfeng He ,&nbsp;Xiang Wang","doi":"10.1016/j.lfs.2025.123830","DOIUrl":"10.1016/j.lfs.2025.123830","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Pathological myocardial hypertrophy and cardiac remodeling are a maladaptive response to stressors such as hypertension and genetic mutations, characterized by cardiomyocyte enlargement, fibrosis, cardiomyocyte apoptosis and impaired cardiac function. Rab26, a small GTPase, plays a crucial role in vesicle trafficking, secretion and apoptosis. However, its role in myocardial hypertrophy and cardiac remodeling remains unclear.</div></div><div><h3>Methods</h3><div>Transverse aortic constriction (TAC) model was employed to induce myocardial hypertrophy and cardiac remodeling, with functional and histological assessments. Cardiac-specific Rab26 overexpression was achieved via AAV9-cTnT-Rab26 delivery, while Rab26 knockout was used for loss-of-function analysis. Molecular mechanisms were explored using protein interaction studies, fluorescence co-localization, and protease inhibition assays.</div></div><div><h3>Results</h3><div>Our findings indicated a significant downregulation of Rab26 protein expression in the disease model, while its mRNA levels remained unaltered. Notably, cardiac-specific overexpression of Rab26 led to improved cardiac function, decreased cardiac fibrosis, suppressed myocardial hypertrophy and cardiomyocyte apoptosis. Furthermore, the knockout of Rab26 aggravated myocardial hypertrophy and cardiac remodeling. At the mechanistic level, Rab26 facilitates lysosomal translocation and degradation of eEF1A. Additionally, eEF1A silencing eliminated the protective effect of Rab26 on the heart. Comprehensive evaluation revealed the critical role of the Rab26-eEF1A axis in mediating pathological myocardial hypertrophy and cardiac remodeling.</div></div><div><h3>Conclusions</h3><div>This study suggests that Rab26 prevents cardiac remodeling and dysfunction under pressure overload by promoting the lysosome translocation and degradation of eEF1A. Targeting the Rab26-eEF1A axis thus provides a potential strategy for preventing or reversing myocardial hypertrophy and cardiac remodeling.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123830"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560510","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":"Regulatory mechanism of ferroptosis in acute kidney injury and potential therapeutic strategies","authors":"Wendi Zhong ,&nbsp;Zihuang Xie ,&nbsp;Siqi Wei ,&nbsp;Tian Zhong ,&nbsp;Tao Jiang","doi":"10.1016/j.lfs.2025.123828","DOIUrl":"10.1016/j.lfs.2025.123828","url":null,"abstract":"<div><div>Ferroptosis is a type of iron-dependent programmed cell death distinguished by increased oxidative stress and the pathological accumulation of lipid peroxides within the cell membrane. Emerging evidence suggests a strong link between ferroptosis and both the occurrence and progression of acute kidney injury (AKI). However, many outstanding issues remain to be solved in the development of drugs that target ferroptosis. Therefore, it is imperative to present a comprehensive overview of the most recent advancements in the field of ferroptosis. In this review, we systematically summarize the predisposing factors and defense mechanisms of ferroptosis in AKI. Moreover, we focused on the role of specific regulators related to ferroptosis, including STING, CX3CL1, FXR, and CD36, in AKI. These regulatory factors may be potential targets for treating AKI in the future. Additionally, potential strategies for preventing AKI by targeting ferroptosis were also highlighted in this study. Numerous studies have demonstrated that targeting ferroptosis to alleviate inflammation and renal fibrosis, modulate metabolic reprogramming, and regulate reactive oxygen species may represent an effective strategy for mitigating the progression of AKI. These findings offer novel potential targets and therapeutic strategies for managing AKI through ferroptosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123828"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536201","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":"Identification of UBE3C as an E3 ubiquitin ligase for mutant BRAF","authors":"Do Yeon Kim ,&nbsp;Hyeseon Yun ,&nbsp;Ji-Eun You ,&nbsp;Dong-In Koh ,&nbsp;Yea Seong Ryu ,&nbsp;Dong-Hoon Jin","doi":"10.1016/j.lfs.2025.123827","DOIUrl":"10.1016/j.lfs.2025.123827","url":null,"abstract":"<div><div>V-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations have been implicated in a variety of cancer types, with the BRAF V600E (BRAF^V600E) mutation being particularly prevalent and recognized as a significant therapeutic target. BRAF inhibitors, such as Vemurafenib, represent a targeted therapeutic option for patients harboring this mutation. While these treatments often elicit a substantial initial response, they are frequently followed by the rapid development of resistance, which is mediated by various regulatory mechanisms. As a result, the pathways governing the BRAF^V600E remain poorly understood, thereby complicating strategies to counteract resistance. In the current study, we employed a tandem affinity purification approach to demonstrate that UBE3C interacts with BRAF^V600E. Our findings indicate that UBE3C binds to the kinase domain of BRAF^V600E and facilitates its ubiquitination. We further assessed the clinical significance of both BRAF^V600E and UBE3C across various models. Additionally, we established that the stability of BRAF^V600E is contingent upon the activity of heat shock protein 90 (HSP90) and is modulated by UBE3C expression. These results suggest that targeting UBE3C may provide a novel strategy to overcome secondary resistance to the BRAF inhibitor Vemurafenib. Our findings indicate that UBE3C plays a critical role in tumor biology and may offer a new avenue for managing acquired resistance in patients with BRAF-mutant cancers.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123827"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536122","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 role of histone modifications in the development of abdominal aortic aneurysm","authors":"Zhang Qiumei ,&nbsp;Zhu Qian ,&nbsp;Zhang Yongjie ,&nbsp;Li Nan","doi":"10.1016/j.lfs.2025.123829","DOIUrl":"10.1016/j.lfs.2025.123829","url":null,"abstract":"<div><div>Cardiovascular diseases with their related secondary complications are the main causes of morbidity and mortality worldwide. Abdominal aortic aneurysm (AAA) belongs to the cardiovascular diseases and causes approximately 1.3 % of all deaths among men between 65 and 85 years old in developed countries [<span><span>1</span></span>]. The pathogenesis of AAA mainly attributes to pathological dilation of the abdominal aorta, which will further lead to a high mortality rate up to 85 % due to excessive dilation and rupture [<span><span>2</span></span>]. A criterion was proposed in 1991 that AAA infrarenal aorta diameter should be 1.5 times the normal diameter [<span><span>3</span></span>], and McGregor additionally defined AAA as an aorta with a diameter greater than 30 mm in the infrarenal segment [<span><span>4</span></span>]. Although the diagnosis of AAA seems conclusive, there is no specific treatment to prevent AAA expansion. Elective aortic repair operation is conditional recommended when the aneurysm diameter reaches 55 mm in men, 50 mm in women or grows by 6 mm to 8 mm per year [<span><span>5</span></span>]. However, small aneurysms probably also grow rapidly or rupture at a high risk, and even some patients die from aneurysm rupture before they manifest surgical indications. Thus, controlling risk factors and exploring novel therapeutic approaches gradually substitute as key directions for aneurysm treatment. Smoking, hypertension, age and gender have been identified as the common risk factors during AAA progression in the past decades [<span><span>6</span></span>], but the mechanisms how these hazards contribute to pathological dilatation of abdominal aortas remain unclear. Interestingly, histone modifications have recently emerged as an important link between the intrinsic genetic landscape and extrinsic risk factors, and a plethora of studies have been dedicated to exploring the role of histone modifications in AAA pathogenesis. In this review, current progress on the contribution of histone modifications to the regulation of AAA will be summarized.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123829"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560511","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":"Targeting FOXP3 in glioblastoma: Blockade of tumor intrinsic effects boosts response to chemo-radiotherapy","authors":"Matías Garcia Fallit ,&nbsp;Jorge A. Peña Agudelo ,&nbsp;Alejandro J. Nicola Candia ,&nbsp;Nazareno Gonzalez ,&nbsp;Melanie Pérez Küper ,&nbsp;Yamila Zampini ,&nbsp;Ana Clara Romero ,&nbsp;Cristian Sobarzo ,&nbsp;Ivana Sánchez Rojas ,&nbsp;Hebe Durán ,&nbsp;Marina Perona ,&nbsp;Luisina Belén Ripari ,&nbsp;Guillermo A. Videla-Richardson ,&nbsp;Flavia A. Zanetti ,&nbsp;Teresa Lozano ,&nbsp;Noelia Casares ,&nbsp;Juan José Lasarte ,&nbsp;Marianela Candolfi","doi":"10.1016/j.lfs.2025.123822","DOIUrl":"10.1016/j.lfs.2025.123822","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Although this disease carries a dismal prognosis due to its highly invasive nature and resistance to therapy, no significant therapeutic advances have emerged in the last 20 years. The transcription factor Forkhead box protein P3 (FOXP3), known for its central role in the immunosuppressive activity of regulatory T cells (Tregs), has also been detected in tumor cells, including GBM cells. However, the intrinsic role of FOXP3 in GBM cells is poorly understood. Thus, we aimed to evaluate the effect of FOXP3 blockade in GBM. Meta-analysis of transcriptomic data indicated that FOXP3, which expression was higher in GBM biopsies than in normal brain, was associated with worse prognosis and chemo-resistance. It also correlated with the expression of markers of immune-suppression and epithelial-mesenchymal transition. Expression of FOXP3 in GBM cell lines and patient-derived cultures was upregulated by chemo- and radiotherapy, and its blockade using a cell penetrating peptide (P60) inhibited GBM cell migration, induced cytotoxicity and enhanced radio- and chemo-sensitivity. To improve the local availability of P60, we developed an adenoviral vector (Ad.P60) that enhanced the apoptotic response of GBM cells and reduced chemoresistance. Local treatment with Ad.P60 in mice bearing intracranial GBM reduced Treg infiltration, inhibited tumor growth and improved chemosensitivity to cisplatin, leading to long-term survival with combined chemo-gene therapy without generating neurotoxicity. Our results suggest that FOXP3 emerges as a dual-function molecule that could improve GBM response to standard treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123822"},"PeriodicalIF":5.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517475","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":"Laser-generated singlet oxygen is protective against beta-amyloid neurotoxicity","authors":"Olga A. Stelmashchuk ,&nbsp;Viktor V. Dremin ,&nbsp;Andrey Y. Abramov","doi":"10.1016/j.lfs.2025.123823","DOIUrl":"10.1016/j.lfs.2025.123823","url":null,"abstract":"<div><div>β-Amyloid is the peptide which forms extracellular senile plaques in Alzheimer's disease. Link of the β-amyloid to inherited form of Alzheimer's disease and neurotoxicity of aggregated peptide has been suggested to the involvement of β-amyloid in the mechanism of pathology of this devastating disease. The toxicity of aggregated β-amyloid is triggered by changes in calcium signal, mitochondrial energy metabolism and oxidative stress. Laser (1267 nm)-induced singlet oxygen is shown to be able to modify proteins and accelerate energy metabolism that potentially may modify the effects of β-amyloid. Using primary co-culture of neurons and astrocytes we studied the effect of laser-generated singlet oxygen on β-amyloid-induced calcium signal, mitochondrial energy metabolism and oxidative stress. We have found that singlet oxygen prevents aggregation of the full peptide βA 1–42, reduces the effect of β-amyloid on cytosolic and mitochondrial calcium elevation, reduces mitochondrial depolarization and depletion of NADH in mitochondria. As result it protected neurons and astrocytes against β-amyloid-induced cell death. Thus, singlet oxygen could play neuroprotective role.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123823"},"PeriodicalIF":5.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502188","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":"Mechanistic insights into the renoprotective effects of artesunate in cisplatin-induced acute kidney injury","authors":"Hetao Chen ,&nbsp;Ran Guo ,&nbsp;Chenning Zhang ,&nbsp;Lei Zhang ,&nbsp;Hongxia Hu ,&nbsp;Peipei Du ,&nbsp;Jiajia Duan ,&nbsp;Lulu Chen ,&nbsp;Xiao Ma ,&nbsp;Juan Xue ,&nbsp;Yanwen Mao ,&nbsp;Tao Jiang","doi":"10.1016/j.lfs.2025.123820","DOIUrl":"10.1016/j.lfs.2025.123820","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a severe clinical syndrome marked by rapid renal function decline. Cisplatin (Cis) is a commonly used chemotherapy agent; however, its clinical application has been restricted due to its nephrotoxicity. Artesunate (ART), derived from <em>Artemisia annua</em>, has potent anti-inflammatory and antioxidant properties. However, its potential to mitigate cisplatin-induced AKI has yet to be fully investigated. This study investigates ART's protective effects against cisplatin-induced AKI and explores its molecular mechanisms. In vivo experiments on C57BL/6 mice were divided into control, cisplatin, and cisplatin + ART groups with different doses. Kidney tissues were analyzed histologically and molecularly. In vitro, HK-2 cells were used to assess cell viability, apoptosis, oxidative stress, and ferroptosis. Network pharmacology and molecular docking predicted ART's targets and interactions. Results demonstrated that ART significantly reduced serum creatinine (Scr) and blood urea nitrogen (BUN) levels, while concurrently improving renal histopathological features. In vitro, ART enhanced cell viability, reduced apoptosis, and decreased reactive oxygen species (ROS). ART increased glutathione (GSH) levels and reduced malondialdehyde (MDA) and Fe²⁺ levels. ART restored mitochondrial membrane potential and ultrastructure in cisplatin-treated cells and upregulated key proteins in the ferroptosis pathway, including GSK3β, PARP1, SLC7A11, and GPX4. Molecular docking studies predict that ART interacts with GSK3β and PARP1. ART significantly alleviates cisplatin-induced acute kidney injury by inhibiting ferroptosis through the GSK3β/PARP1/SLC7A11 signaling pathway. This study provides strong evidence for the therapeutic potential of ART in AKI and highlights the need for further research into its molecular mechanisms and clinical applications.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123820"},"PeriodicalIF":5.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512120","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 role of machine learning in predictive toxicology: A review of current trends and future perspectives","authors":"Olawale M. Ajisafe ,&nbsp;Yemi A. Adekunle ,&nbsp;Eghosasere Egbon ,&nbsp;Covenant Ebubechi Ogbonna ,&nbsp;David B. Olawade","doi":"10.1016/j.lfs.2025.123821","DOIUrl":"10.1016/j.lfs.2025.123821","url":null,"abstract":"<div><div>Adverse drug reactions (ADRs) are a major challenge in drug development, contributing to high attrition rates and significant financial losses. Due to species differences and limited scalability, traditional toxicity testing methods, such as in vitro assays and animal studies, often fail to predict human-specific toxicities accurately. The emergence of artificial intelligence (AI) and machine learning (ML) has introduced transformative approaches to predictive toxicology, leveraging large-scale datasets such as omics profiles, chemical properties, and electronic health records (EHRs). These AI-powered models provide early and accurate identification of toxicity risks, reducing reliance on animal testing and improving the efficiency of drug discovery. This review explores the role of AI models in predicting ADRs, emphasizing their ability to integrate diverse datasets and uncover complex toxicity mechanisms. Validation techniques, including cross-validation, external validation, and benchmarking against traditional methods, are discussed to ensure model robustness and generalizability. Furthermore, the ethical implications of AI, its alignment with the 3Rs principle (Replacement, Reduction, and Refinement), and its potential to address regulatory challenges are highlighted. By expediting the identification of safe drug candidates and minimizing late-stage failures, AI models significantly reduce costs and development timelines. However, challenges related to data quality, interpretability, and regulatory integration persist. Addressing these issues will enable AI to fully revolutionize predictive toxicology, ensuring safer and more effective drug development processes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123821"},"PeriodicalIF":5.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491203","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}