Life sciences最新文献

{"title":"ASK1 inhibition by selonsertib attenuates elastase-induced emphysema in mice","authors":"Priscilla Cristine de Oliveira Mineiro ,&nbsp;Vanderlei da Silva Fraga-Junior ,&nbsp;Aline de Oliveira Pontes Cardoso ,&nbsp;Christopher Mark Waters ,&nbsp;Christina Maeda Takiya ,&nbsp;Cláudia Farias Benjamim ,&nbsp;Helber da Maia Valenca ,&nbsp;Manuella Lanzetti ,&nbsp;J.A. Moraes ,&nbsp;S.S. Valenca","doi":"10.1016/j.lfs.2025.123600","DOIUrl":"10.1016/j.lfs.2025.123600","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, with its most severe form being pulmonary emphysema, for which no effective treatment currently exists. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in lung inflammation and injury. Here, we investigated the experimental treatment of elastase-induced emphysema in mice with selonsertib, an ASK1 inhibitor. Animals received intratracheal elastase and were subsequently treated with intranasal selonsertib at different doses. On day 21, bronchoalveolar lavage fluid and lung tissues were collected for histological and biochemical analyses. Results showed that elastase-instilled mice developed pulmonary emphysema, whereas treatment with selonsertib at a dose of 2 mg/kg significantly reduced mean alveolar diameter. Moreover, higher doses of selonsertib were effective in reducing inflammatory cytokines (CX3CL1, IL-6, CCL2, and IL-1β), reactive oxygen species, and apoptosis. These findings suggest that ASK1 plays a critical role in the development of elastase-induced emphysema in mice and could be a target for COPD treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123600"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795240","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 the use of nanoparticles for specific cell-target delivery of anti-cancer agents","authors":"Ana Belen Diaz-Ruano ,&nbsp;Eliana Gomez-Jimenez ,&nbsp;Gloria Llamas-Jimenez ,&nbsp;Arena Ramirez-Muñoz ,&nbsp;Pablo Espejo-Hijano ,&nbsp;Alfonso Rubio-Navarro ,&nbsp;Manuel Picon-Ruiz","doi":"10.1016/j.lfs.2025.123604","DOIUrl":"10.1016/j.lfs.2025.123604","url":null,"abstract":"<div><div>In recent decades, cancer has emerged as one of the leading causes of death in developed countries. To revert this progression, scientists have focused on the design of new strategies for early detection of this disease and the development of more effective treatments for its eradication. Regarding the latter, one of the main research efforts has been directed toward designing more specific delivery systems for the administration of anti-tumoral agents. In this sense, the efficacy of conventional therapies used for cancer treatment, such as chemotherapy, immune checkpoint inhibitors and radiation therapy, are often limited by their lack of specificity and their potential to cause adverse secondary effects on healthy tissues. Therefore, designing specific cell-targeted delivery systems for anti-tumoral agents presents a promising approach to overcoming the limitations of conventional cancer therapies. In this review we summarize the advances in the use of nanoparticles for Specific Cell-Target Delivery of anti-tumoral agents from in vitro to clinical studies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123604"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogram to heal: Macrophage phenotypes as living therapeutics","authors":"Sheyda Ghamangiz ,&nbsp;Abbas Jafari ,&nbsp;Hadi Maleki-Kakelar ,&nbsp;Hadi Azimi ,&nbsp;Ebrahim Mazloomi","doi":"10.1016/j.lfs.2025.123601","DOIUrl":"10.1016/j.lfs.2025.123601","url":null,"abstract":"<div><div>Macrophages represent a crucial cell type within the immune system, exhibiting significant adaptability that allows for the transformation into various phenotypes in response to their surrounding environment. This review investigates the characteristics of various macrophage phenotypes and their functional roles in disease pathogenesis and resolution. The M1 phenotype, recognized for its inflammatory attributes, plays a pivotal role in combating infections and tumors; however, it may also contribute to tissue injury, persistent inflammation, and the pathogenesis of autoimmune and inflammatory diseases. Conversely, the M2 phenotype is associated with anti-inflammatory activities and tissue repair processes. But this is not the end of the story and researches illustrated novel phenotypes that may provide new approaches and therapeutic opportunities. Recent progress in characterizing distinct macrophage phenotypes has enabled the development of innovative therapeutic strategies for chronic inflammatory conditions, autoimmune disorders, and cancers. This review underscores the critical role of macrophage polarization, illustrating how various stimuli can influence macrophage fate and modify their responses. Additionally, it explores the implications of macrophage plasticity on disease progression and treatment efficacy. A comprehensive understanding of these dynamics is essential for the advancement of targeted immunotherapies, which possess the potential to transform treatment strategies for a variety of medical conditions.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123601"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783702","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":"Efficacy and limitations of SARS-CoV-2 vaccines - A systematic review","authors":"Muhammad Azeem ,&nbsp;Patrizia Cancemi ,&nbsp;Farwa Mukhtar ,&nbsp;Sefora Marino ,&nbsp;Emanuela Peri ,&nbsp;Giulia Di Prima ,&nbsp;Viviana De Caro","doi":"10.1016/j.lfs.2025.123610","DOIUrl":"10.1016/j.lfs.2025.123610","url":null,"abstract":"<div><div>The emergence of the SARS-CoV-2 virus worldwide led to the call for the development of effective and safe vaccines to contain the spread and effects of COVID-19. Using information from 40 publications, including clinical trials and observational studies from 2019 to 2024, this review assesses the effectiveness, safety, and limitations of four major vaccines: Sinopharm (BBIBP-CorV), Moderna (mRNA-1273), Pfizer-BioNTech (BNT162b2), and CoronaVac. Pfizer-BioNTech and Moderna's mRNA vaccines proved to be more effective than others; Moderna's vaccines showed an efficacy of 94.1 % against symptomatic infection, while Pfizer-BioNTech's vaccines showed an efficacy of up to 95 %, against severe diseases and hospitalization. These vaccinations, which included protection against Omicron and Delta variants, offered notable protection against serious illness, hospitalization, and mortality. Severe adverse events were rare while most adverse events were mild to moderate, such as headaches, fatigue, and localized reactions.</div><div>In contrast, inactivated virus vaccines such as Sinopharm and CoronaVac with efficacies ranging from 50 to 79 % against symptomatic infection showed lower levels of effectiveness. In Phase 3 trial, Sinopharm showed 72.8 % efficacy, whereas CoronaVac demonstrated roughly 67 % efficacy in population against hospitalization and severe disease. Booster doses were required for adequate immunological response, especially against novel strains, as these vaccinations proved to be less effective in older populations. They showed considerable safety profiles, with mild side effects, but their low immunogenicity is concerning. This review emphasizes the importance of continuously evaluating vaccines in response to the evolving virus, essential for improving international immunization programs.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123610"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of branched-chain amino acids in cardio-oncology: A review","authors":"Jiaqi Xu ,&nbsp;Yu Wang ,&nbsp;Jing Zhang ,&nbsp;Jingyi Tang ,&nbsp;Zhongyan Zhou","doi":"10.1016/j.lfs.2025.123614","DOIUrl":"10.1016/j.lfs.2025.123614","url":null,"abstract":"<div><div>Cancer and cardiovascular diseases (CVDs) are global health challenges. In cancer patients, CVD is the second leading cause of death following disease progression. There are few specialized services for cardio-oncology patients worldwide currently. Branched-chain amino acids (BCAAs) are essential amino acids that promote protein synthesis and energy homeostasis. The disruption of BCAAs metabolism facilitates the development of cancer and CVDs while the benefit of BCAA supplement is full of controversy. In this review, we summarized BCAA-related studies in cardiometabolism, cancer and chemotherapy-induced cardiotoxicity, and provided our perspectives on the roles of BCAAs in cardio-oncology. We find that supplementation of BCAAs presents protective effects in cardiometabolic diseases, while the influence on cancer is intricate and varies across different types of cancers. Large-scale clinical studies are needed to understand the long-term effects of BCAA intake and its impact on different stages of the disease. BCAAs have potential to mitigate chemotherapy-induced cardiotoxicity. Continued research is still essential to understand the precise mechanisms, determine optimal dosage and timing, and assess the effectiveness of BCAA supplement in cardio-oncology, in particular clinical research.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123614"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795222","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 gut-immune-heart modulate cardiac remodeling after acute myocardial infarction","authors":"Jinmei Yu,&nbsp;Lin Zhou,&nbsp;Guo Li,&nbsp;Zaiyi Chen,&nbsp;Muhammad Saqib Mudabbar,&nbsp;Le Li,&nbsp;Xinyi Tang,&nbsp;Mimi Jiang,&nbsp;Guolan Zhang,&nbsp;Xing Liu","doi":"10.1016/j.lfs.2025.123606","DOIUrl":"10.1016/j.lfs.2025.123606","url":null,"abstract":"<div><div>The gut microbiota interacts with the host to regulate disease and health status. An increasing number of studies have recognized the bidirectional regulation between gut microbiota and immune cells, which plays a significant role in the etiology and prognosis of diseases. Gut microbiota is also a crucial regulatory factor in cardiovascular diseases. After acute myocardial infarction, myocardial and endothelial damage rapidly triggers an inflammatory response, activating the immune system and disrupting the gut microbiota ecology, thereby affecting cardiac remodeling after acute myocardial infarction and potentially leading to heart failure. We have elucidated the regulatory mechanisms of complex intercellular networks in the immune system during cardiac remodeling after acute myocardial infarction. Furthermore, this research examines the roles and mechanisms of gut microbiota, immune cells, and gut metabolites in relation to cardiac remodeling and heart failure after myocardial infarction. Finally, we discuss the potential of targeting gut immune cells as an effective approach to prevent and treat heart failure after acute myocardial infarction in the future, through methods such as dietary regulation, probiotic supplementation, and microbiota transplantation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123606"},"PeriodicalIF":5.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting vulnerability in tumor therapy: Dihydroorotate dehydrogenase","authors":"Fu Lin ,&nbsp;Jiaxin Li ,&nbsp;Lei Zhou ,&nbsp;Rigui Yi ,&nbsp;Yingge Chen ,&nbsp;Shuai He","doi":"10.1016/j.lfs.2025.123612","DOIUrl":"10.1016/j.lfs.2025.123612","url":null,"abstract":"<div><div>Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the de novo pyrimidine biosynthetic pathway and a recognized therapeutic target in various diseases. In oncology research, DHODH has gained increasing importance and become a hot target for various tumor therapy studies. This review highlights three key points: (1) DHODH enables its diverse biological functions through its unique structural features and dominates the regulation of tumor metabolism and cell fate; (2) DHODH activates oncogenic signals, drives metastatic adaptation, and remodels drug resistance networks in tumors, making it a metabolic-signaling dual hub; and (3) DHODH inhibitors have shown significant efficacy in preclinical models of various tumors but face multiple challenges in clinical trials, including drug-related limitations and external constraints. Given these challenges, future research should explore DHODH inhibitors as a foundation for overcoming technological and translational barriers while establishing a systematic framework for the clinical application of DHODH-targeted tumor therapies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123612"},"PeriodicalIF":5.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788486","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":"Decoding Proteomic cross-talk between hypobaric and normobaric hypoxia: Integrative analysis of oxidative stress, cytoskeleton remodeling, and inflammatory pathways","authors":"Poornima Sharma,&nbsp;Swaraj Mohanty,&nbsp;Yasmin Ahmad","doi":"10.1016/j.lfs.2025.123611","DOIUrl":"10.1016/j.lfs.2025.123611","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the differential regulation of proteomic landscapes elicited by hypobaric hypoxia (HH) and normobaric hypoxia (NH) and to shed light on the molecular cross-talk underlying pre-acclimatization strategies.</div></div><div><h3>Materials and methods</h3><div>Label-free LCMS-MS quantitative proteomics was employed to evaluate the lung tissues of SD rats (<em>n</em> = 6) subjected to 6 h of acute HH at 25,000 ft associated with reduced barometric pressure, 282 mmHg, and NH at 8 % FiO2.</div></div><div><h3>Key findings</h3><div>Our findings indicate that NH facilitated the minimal downregulation of proteins involved in maintaining pulmonary cytoskeleton integrity, including calpain 2, vitronectin, and beta-arrestin 1, whereas HH leads to severe downregulation of these proteins, causing a greater cytoskeleton disruption. Proteins contributing to redox homeostasis such as iNOS and SOD, were upregulated in both hypoxic conditions. However, SIRT1-mediated ROS-triggered proteins, including FOXO1 and FOXO4, exhibited upregulation in HH and downregulation in NH. Other proteins, HIF-1α and IDH, were upregulated in HH compared to NH. Additionally, Hemopexin was severely downregulated in HH relative to NH.</div></div><div><h3>Significance</h3><div>For the first time, this study uncovers the comparative proteomic analysis of two distinct pre-acclimatization interventions by employing varied hypoxia modeling strategies highlighting the key molecular mechanism involved in HH acclimatization induced by differential hypoxia simulating technique.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123611"},"PeriodicalIF":5.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786070","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":"Dexmedetomidine inhibits ferroptosis through the Akt/GSK3β/Nrf2 axis and alleviates adriamycin-induced cardiotoxicity","authors":"Xuefeng Cao ,&nbsp;Liang Zhao ,&nbsp;Jian Zhou ,&nbsp;Shi Ding ,&nbsp;Ying Sun ,&nbsp;Yang Ma ,&nbsp;Zijian Ma ,&nbsp;Hancheng Liu ,&nbsp;Tianxin Dong ,&nbsp;Aijing Luo ,&nbsp;Yan Li ,&nbsp;Bo Fang","doi":"10.1016/j.lfs.2025.123609","DOIUrl":"10.1016/j.lfs.2025.123609","url":null,"abstract":"<div><div>The cardiotoxicity of Adriamycin(ADR) limits its clinical application, and its molecular mechanism is not very clear. At present, Dexrazoxane (DXZ) is the only approved drug to prevent ADR-induced cardiotoxicity (DIC), but it also has serious adverse reactions. Therefore, it is a key scientific challenge to find a drug with strong myocardial protection, few adverse reactions and no effect on the anti-tumor effect of ADR. In this study, we established the DIC model in rats. Cardiomyocyte hypertrophy and myocardial fibrosis increased significantly, and MDA and LDH increased significantly in serum. Dexmedetomidine (DEX) is a carbohydrate with multiple biological activities that can significantly improve the above DIC process. Echocardiography confirmed that DEX could reverse the changes of ESV, EDV, EF and FS induced by ADR. In vitro, experiments confirmed that DEX reversed the upregulation of ANP, BNP, MHC and Collagen III protein levels induced by ADR. DEX improves DIC by inhibiting ferroptosis. Erastin, a ferroptosis agonist, confirmed that DEX improved DIC by inhibiting ferroptosis. Mechanically, DEX increases the expression of Nrf2 in the nucleus through the Akt/Gsk3β signalling axis, thereby regulating ferroptosis in cardiomyocytes. In addition, DEX can improve DIC while not affecting the anti-tumor effect of ADR.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123609"},"PeriodicalIF":5.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768145","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":"Linagliptin mitigates lipopolysaccharide-induced acute kidney injury in mice: Novel renal BDNF/TrkB/NRF2-dependent antioxidant, anti-inflammatory, and antiapoptotic mechanisms","authors":"Nada M. Kamel ,&nbsp;Sarah S. El-Sayed ,&nbsp;Shimaa O. Ali ,&nbsp;Rabab H. Sayed ,&nbsp;Maheera H. Safwat","doi":"10.1016/j.lfs.2025.123602","DOIUrl":"10.1016/j.lfs.2025.123602","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a common complication associated with sepsis, yet no effective treatment is currently available. The primary mechanisms involved in lipopolysaccharide (LPS)-induced septic AKI are oxidative stress, inflammation, and apoptosis. This study aimed to investigate the potential renoprotective effects of linagliptin, an antidiabetic dipeptidyl peptidase (DPP)-4 inhibitor, against LPS-induced AKI with special emphasis on renal brain-derived neurotrophic factor (BDNF)/ nuclear factor erythroid 2-related factor 2 (NRF2) axis. Mice were divided into control, LPS, LPS + linagliptin, and LPS + linagliptin+ANA-12 (tropomyosin receptor kinase B (TrkB) antagonist) groups. Our results revealed that linagliptin, partially through BDNF augmentation, ameliorated AKI, evidenced by the improved histological structure and function of the kidney where serum creatinine, blood urea nitrogen, cystatin C, and renal kidney injury molecule-1were decreased with increased serum albumin. These improvements result from Glucagon-like peptide-1/BDNF/TrkB-mediated NRF2 activation, enhancing antioxidant, anti-inflammatory, and antiapoptotic pathways. Linagliptin, through NRF2 augmentation, suppressed renal myeloperoxidase, malondialdehyde, NLR Family pyrin domain-containing 3 inflammasome, nuclear factor-kappaB, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, B-cell lymphoma 2 (Bcl2)-associated X protein, while boosting the antioxidant glutathione and the antiapoptotic Bcl2 contents. The administration of ANA-12 before linagliptin partially reversed these beneficial effects. Accordingly, our results suggest that linagliptin has therapeutic potential in managing LPS-induced AKI. Furthermore, they provide insights into its underlying mechanisms, highlighting renal BDNF signaling as a potential therapeutic target through downstream NRF2 enhancement and its associated antioxidant, anti-inflammatory, and antiapoptotic effects.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123602"},"PeriodicalIF":5.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768286","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}