Life sciences最新文献

{"title":"Unraveling cervical inflammation in HIV-infected women: The regulatory role of miR-204‐5p and miR-3691‐3p","authors":"Kadambari Akolkar ,&nbsp;Sudipta Sonar ,&nbsp;Amrita Rao ,&nbsp;Megha Mamulwar ,&nbsp;Ujjwala Ghule ,&nbsp;Rajani Bagul ,&nbsp;Pallavi Vidhate ,&nbsp;Aditi Bedekar ,&nbsp;Himadri Bal ,&nbsp;Arati Mane ,&nbsp;Madhuri Thakar ,&nbsp;Vandana Saxena","doi":"10.1016/j.lfs.2025.123774","DOIUrl":"10.1016/j.lfs.2025.123774","url":null,"abstract":"<div><div>Genital inflammation not only increases the risk of HIV acquisition, reduces antiretroviral efficacy, but also poses risks for other STIs, highlighting the need to understand underlying regulatory mechanisms. MicroRNAs/miRNAs are important regulators of various cellular processes, including inflammation; however their role in HIV-driven cervical inflammation remains unclear. Using transcriptome analysis and various bioinformatics tools, we identified key inflammation-associated miRNAs, molecular pathways and regulatory networks in the cervical cells of 24 HIV-infected women <em>vis-a-vis</em> 23 HIV-uninfected women. RNA-sequencing deciphered a dysregulated profile of 8 inflammation-associated miRNAs in cervical cells of HIV-infected women. In line with RNA-sequencing data, RT-PCR confirmed the upregulated expression of hsa-miR-204‐5p and hsa-miR-3691‐3p along with inflammatory markers (IL-1β, IL-6, TNF-α, NF-kB) in cervical cells of HIV-infected women. KEGG analysis revealed involvement of these miRNAs in inflammatory pathways (MAPK, Wnt, PI3K-AKT) and cancer-related pathways. PPI network identified CTNNB1, BCL2, and GSK3B as key hub genes, where GSK3B showed maximum interactions with transcription factors (TF; <em>n</em> = 31). EZH2 and EED were prominent TFs showing highest interactions with hub genes. Drug prediction further suggested Valproic acid, a known GSK3B inhibitor, as a potential therapeutic based on degree of interaction with hub genes. Conclusively, HIV-infected women displayed cervical inflammation, increased miR-204–5p and miR-3691–3p and deregulated inflammatory pathways. Targeting these miRNAs and/or their intermediates might be one of the useful approaches to alleviate cervical inflammation in HIV-infected women, which needs to be examined further.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123774"},"PeriodicalIF":5.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191960","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 impact of preexisting omega-3 fatty acid serum levels on outcomes following out-of-hospital cardiac arrest: A comprehensive investigation","authors":"J. Grabert ,&nbsp;G. Mohsen ,&nbsp;C. Diepenseifen ,&nbsp;U. Heister ,&nbsp;M. Breil ,&nbsp;M. Rohner ,&nbsp;I. Graeff ,&nbsp;J. Kappler ,&nbsp;K. Gutbrod ,&nbsp;P. Dörmann ,&nbsp;J.C. Schewe ,&nbsp;A. Kunsorg ,&nbsp;A. Mayr ,&nbsp;A. Stroemer ,&nbsp;C. Stoppe ,&nbsp;S. Zimmer ,&nbsp;U. Hoffmann ,&nbsp;G.D. Duerr ,&nbsp;M. Wittmann ,&nbsp;M. Velten","doi":"10.1016/j.lfs.2025.123770","DOIUrl":"10.1016/j.lfs.2025.123770","url":null,"abstract":"<div><h3>Background</h3><div>Out-of-hospital cardiac arrest (OHCA) remains a medical challenge with persistently low survival rates. Omega-3 polyunsaturated fatty acids (PUFAs) confer cardiac and neuroprotection trough their anti-inflammatory and anti-oxidative effects. This prospective multicenter study aimed to evaluate the impact of pre-existing PUFA serum levels on OHCA survival and neurological outcome.</div></div><div><h3>Methods</h3><div>Blood samples were collected from OHCA patients immediately following the return of spontaneous circulation (ROSC) for the analysis of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) serum levels. Univariate and multivariate analyses incorporated demographic and resuscitation data. Follow-up assessments were conducted at 1, 6, 12 and 24 months post-OHCA.</div></div><div><h3>Results</h3><div>DHA levels after ROSC were significantly higher in patients who survived OHCA at 1 month and 12 months (<em>p</em> = 0.01 and <em>p</em> = 0.02, respectively). Similarly, EPA levels after ROSC were consistently higher in survivors across all follow-up time points (1 month: <em>p</em> = 0.04, 6 months: <em>p</em> = 0.03, 12 months: <em>p</em> &lt; 0.001, 24 months: p = 0.03) compared to deceased patients at the corresponding time points. Multivariate analysis identified younger age (p = 0.03, OR 1.1), shorter no-flow time (<em>p</em> = 0.02, OR 1.3) and shorter cardiopulmonary resuscitation (CPR) duration (p = 0.02, OR 1.1) as strong predictors of survival following OHCA (numbers exemplarily for 12 months survival). Furthermore, the 77 % of survivors exhibited favorable neurological outcomes at 12 months post-OHCA.</div></div><div><h3>Conclusion</h3><div>This study demonstrates a significant association between preexisting PUFA serum levels during OHCA and long-term outcomes following ROSC, highlighting their potential cardio- and neuroprotective roles. These findings underscore the need for further research to investigate potential therapeutic applications in the field of resuscitation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123770"},"PeriodicalIF":5.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187319","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":"Xanthosomes loaded with recombinant TMEM219 for targeting IGFBP-3: A novel approach for targeted drug delivery to ameliorate liver fibrosis","authors":"Armin Mokhtariye ,&nbsp;Jaleh Varshosaz ,&nbsp;Adel Mohammadalipour ,&nbsp;Mohammad Hashemnia ,&nbsp;Mohammad Reza Mofid","doi":"10.1016/j.lfs.2025.123748","DOIUrl":"10.1016/j.lfs.2025.123748","url":null,"abstract":"<div><h3>Aims</h3><div>Insulin-like growth factor binding protein-3 (IGFBP-3) activates hepatic stellate cells, enhancing hepatic fibrogenesis. This research aimed to fabricate IGFBP-3 targeted xanthosomes loaded with transmembrane-protein 219 (TMEM219) to target TGFβ/IGFBP-3 signaling pathway in liver fibrosis.</div></div><div><h3>Materials and methods</h3><div>Recombinant TMEM219 was expressed, purified, and loaded into xanthosomes using thin-film hydration method. MTT assay performed cytotoxicity on the LX-2 cell line. Liver fibrosis was induced in rats via bile duct ligation, followed by intravenous injection: Sham (SH) and Fibrotic (F) with saline, Short-term (ST) and Long-term (LT) TMEM219 loaded in targeted xanthosomes (0.4 mg/kg), Blank targeted xanthosomes (BST and BLT), and free TMEM219 (Free; 0.4 mg/kg). Evaluations included biochemical parameters, histopathology and immunohistochemistry, α-SMA and COL1A1 mRNA expression, serum IGFBP-3 levels, and TGF-β1 protein expression.</div></div><div><h3>Key findings</h3><div>TMEM219-loaded xanthosomes exhibited a particle size of 149.9 nm, zeta-potential of −11.4 mV, and loading efficiency of 71.5 %. MTT assay showed lower cytotoxicity of targeted xanthosomes compared to free TMEM219 (<em>p</em> &lt; 0.05). ST and LT groups significantly improved AST and ALT levels, histopathology (reduced necrosis, fibrogenesis, inflammation), α-SMA and COL1A1 expression, serum IGFBP-3, p-AKT and TGF-β1 expression (<em>p</em> &lt; 0.05, <em>p</em> &lt; 0.01).</div></div><div><h3>Significance</h3><div>Improvements in therapeutic parameters indicated reduced liver fibrosis progression. This study demonstrates that TMEM219-xanthosomes effectively target IGFBP-3, significantly reducing liver fibrosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123748"},"PeriodicalIF":5.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187320","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":"Corrigendum to “Epithelial cells and fibroblasts are both activated via TGF-β1 and GSK-3β pathways differentially in the comorbidity of pulmonary fibrosis with lung adenocarcinoma” [Life Sci. 374 (2025) 123696]","authors":"Chenguang Yang ,&nbsp;Zijian Qin ,&nbsp;Hu Ma ,&nbsp;Huanqin Liu ,&nbsp;Mengdan Hou ,&nbsp;Jing Wei ,&nbsp;Hongyan Guo ,&nbsp;Xiang An ,&nbsp;Feng Yang ,&nbsp;Aijun Yang ,&nbsp;Yamei Dang ,&nbsp;Fangfang Zhang","doi":"10.1016/j.lfs.2025.123719","DOIUrl":"10.1016/j.lfs.2025.123719","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123719"},"PeriodicalIF":5.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183184","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 mechanism of liraglutide on promoting osteogenesis via macrophages polarization under the inflammatory and oxidative stress in osteoporosis","authors":"Siyu Zhu ,&nbsp;Yue Hu ,&nbsp;Zelin Wang ,&nbsp;Qiangbo Tan ,&nbsp;Yaran Zang ,&nbsp;Zijiao Zhang ,&nbsp;Wenqi Fu ,&nbsp;Yuzhu He ,&nbsp;Hui Dong ,&nbsp;Huiying Liu","doi":"10.1016/j.lfs.2025.123717","DOIUrl":"10.1016/j.lfs.2025.123717","url":null,"abstract":"<div><h3>Aims</h3><div>Osteoporosis (OP), is mainly characterized by decreased bone mineral density and bone quality highly correlated with inflammatory and oxidative microenvironment. Liraglutide (Lira), as a glucagon-like peptide-1 receptor agonist, demonstrated an osteogenic effect. This research aims to explore the bidirectional regulatory effects of Lira on immunity and bone in osteoporosis.</div></div><div><h3>Materials and methods</h3><div>The OP model was established by ovariectomy on 8w female C57BL/6J divided into the sham, OVX, OVX + Lira group (n = 30/group). The effects of Lira on inflammation, oxidative stress and bone regeneration on OP were evaluated by Micro CT and histological analysis. The mechanism of Lira on anti-inflammation and anti-oxidation was detected with the primary BMDMs, BMSCs, and MC3T3-E1 cells by WB, RT-PCR, immunofluorescence and RNA seq.</div></div><div><h3>Key findings</h3><div>Lira improves bone formation, regulates macrophage polarization and reduces inflammation and oxidative stress levels in OP mice. Lira inhibits the M1 macrophage polarization of BMDMs by the TNF pathway in primary cells of OP mice, and promoted the osteogenic differentiation of BMSCs. Lira promotes macrophage polarization toward M2 through the decreased CCL2, CXCL10, and NFKBIA in the TNF pathway in LPS-treated BMDMs. Lira reduces heme oxygenase-1 (HO-1) and 4-HNE expression in H₂O₂-treated MC3T3-E1 via macrophage, which induces Nrf2 nuclear translocation. The decreased cleaved caspase-3 and Bax/Bcl-2 indicated that the osteoblast apoptosis was inhibited by Lira. (*<em>p</em> &lt; 0.05, **<em>p</em> &lt; 0.01, ***<em>p</em> &lt; 0.001).</div></div><div><h3>Significance</h3><div>Lira inhibits inflammation and oxidation through decreasing TNF-α pathway of macrophage and Nrf2 translocation of MC3T3-E1, that results in osteogenesis and anti-apoptosis in OP.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123717"},"PeriodicalIF":5.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174365","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":"FAM172A deletion aggravates high fat diet-induced MASLD via the eIF2α-ATF4-FGF21 loop","authors":"Herui Wei ,&nbsp;Meixin Gao ,&nbsp;Shiwei Wang ,&nbsp;Junru Yang ,&nbsp;Zhe Yu ,&nbsp;Mengqi Li ,&nbsp;Hongshan Wei ,&nbsp;Fan Xiao","doi":"10.1016/j.lfs.2025.123763","DOIUrl":"10.1016/j.lfs.2025.123763","url":null,"abstract":"<div><h3>Aims</h3><div>Inhibition of endoplasmic reticulum stress (ERS) can effectively improve the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we attempted to further explore the mechanism of Fam172a in high fat diet (HFD) induced-MASLD.</div></div><div><h3>Materials and methods</h3><div>The correlation between FAM172A and ERS-induced MASLD was tested by WB and qRT-PCR. We utilized wild type (WT) and <em>Fam172a</em> gene knockout (<em>Fam172a</em>^{<em>−/−</em>}) mice to build two models: MASLD model induced by HFD and ERS model induced by tunicamycin (Tm). We evaluated the degree of liver inflammation, steatosis, and lipid accumulation, and key molecules of ERS and apoptosis (Bax/Bcl-2). Based on RNA-seq analysis, we verified downstream target molecules of Fam172a. Co-immunoprecipitation was used to explore the binding protein of Fam172a and its core functional fragment.</div></div><div><h3>Key findings</h3><div>We have found that <em>Fam172a</em>^{<em>−/−</em>} mice with MASLD shows significantly obesity, dysfunction of glucolipid metabolism, severe hepatic inflammation and steatosis, and ERS pathway activation. Similar results are found in the ERS mouse model. We also reveal that <em>Fam172a</em>^{<em>−/−</em>} may significantly up-regulate fibroblast growth factor 21 (<em>Fgf21</em>) expression, probably through activating eukaryotic translation initiation factor 2 alpha (eIF2α). FGF21 can partly counteract <em>Fam172a</em> deletion-induced ERS and hepatic steatosis. Fam172a 1–102 amino acids is the core region to interact with eIF2α.</div></div><div><h3>Significance</h3><div><em>Fam172a</em> gene deletion can promote HFD-induced MASLD via the eIF2α-ATF4 pathway. The expression of <em>Fgf21</em>, up-regulated by the eIF2α-ATF4 pathway, partially inhibit the effects of <em>Fam172a</em> gene deletion via negative feedback loop. Thus, FAM172A may serve as a potential target of MASLD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123763"},"PeriodicalIF":5.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134942","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 axis of miR-30a/AIF-1/TRPC6/calcineurin A/NFAT2 regulated the death modalities and inflammation of renal tubular epithelial cells in diabetic kidney disease via exosome","authors":"Jianbing Hao,&nbsp;Siyu Wang,&nbsp;Xiaojun Guo,&nbsp;Xinyu Guo,&nbsp;Lirong Hao","doi":"10.1016/j.lfs.2025.123760","DOIUrl":"10.1016/j.lfs.2025.123760","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic kidney disease (DKD) is a significant complication of diabetes, marked by inflammation, fibrosis, and cell death in renal tissues. This study aimed to elucidate the regulatory role of miR-30a in DKD, focusing on its impact on monocyte/macrophage activity, key protein expression, exosomes, and renal cell death modalities.</div></div><div><h3>Materials and methods</h3><div>Using <em>db/db</em> mice as a DKD model, miR-30a expression was manipulated through knockout and overexpression techniques. Macrophage activity was evaluated via F4/80 expression and the M1/M2 macrophage ratio. Key proteins (AIF-1, TRPC6, calcineurin A, NFAT2, and NLRP3) were measured in renal tissues and exosomes from blood and urine. In vitro, TCMK-1 cells under high-glucose conditions were used to assess cell death modalities, including autophagy, apoptosis, pyroptosis, and necrosis.</div></div><div><h3>Key findings</h3><div>miR-30a inhibited macrophage activity, with increased F4/80 expression in knockout groups and decreased levels in overexpression groups. The M1/M2 macrophage ratio rose in knockout groups and fell in overexpression groups. miR-30a overexpression reduced key protein levels and urinary albumin (ALB), indicating a protective effect against DKD. Exosome concentration and protein content decreased in miR-30a-overexpressing mice. In vitro findings supported these results, highlighting miR-30a's regulatory effects on AIF-1, Caspase 3, TRPC6, Calcineurin A, NFAT2, and cell death modalities. Exosome secretion from TCMK-1 or RAW264.7 cells was affected by high-glucose conditions, influencing cell death modalities and functions of TCMK-1 cells.</div></div><div><h3>Significance</h3><div>The axis of miR-30a/AIF-1/TRPC6/calcineurin A/NFAT2 regulated death modalities and inflammation of renal tubular epithelial cells in DKD via exosome. miR-30a might be a novel therapeutic target to slow DKD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123760"},"PeriodicalIF":5.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150996","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":"Autophagy in cardiac pathophysiology: Navigating the complex roles and therapeutic potential in cardiac fibrosis.","authors":"Ling-Xuan Dan, Song-Ping Xie","doi":"10.1016/j.lfs.2025.123761","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123761","url":null,"abstract":"<p><p>Cardiac fibrosis is a critical factor in cardiac structural remodeling and dysfunction, closely associated with the progression of various cardiovascular diseases (CVDs), including heart failure and myocardial infarction (MI). It is characterized by excessive extracellular matrix (ECM) deposition, which disrupts normal cardiac architecture and impairs cardiac function. Autophagy, a cellular degradation and recycling mechanism, is essential for maintaining cardiac homeostasis, mitigating stress responses, and preventing cellular damage. Recent studies have revealed a significant link between autophagy and cardiac fibrosis, suggesting that autophagic dysregulation can exacerbate fibrosis by promoting fibroblast activation and ECM accumulation. Conversely, proper autophagic activity may attenuate cardiac fibrosis by removing damaged cellular components and regulating fibrotic signaling pathways. This review examines the role of autophagy in cardiac fibrosis. It also emphasizes potential pharmacological strategies that can be used to modulate autophagic processes. These strategies may serve as therapeutic approaches for treating cardiac fibrosis, with the ultimate goal of preventing excessive fibrosis and enhancing cardiac function.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123761"},"PeriodicalIF":5.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150994","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":"Corrigendum to “Urine protein in patients with type I hypersensitivity is indicative of reversible renal tube injury” [Life Sci. 305 (2022) 120735]","authors":"Yong Cao ,&nbsp;Li Shao ,&nbsp;Mei Xin ,&nbsp;Yilun Zhang ,&nbsp;Yanhua Xu ,&nbsp;Yang Song ,&nbsp;Hui Lu ,&nbsp;Yiwei Wang ,&nbsp;Ying Xia ,&nbsp;Meixing Zhang ,&nbsp;Yinshi Guo ,&nbsp;Lianyun Wang ,&nbsp;Zhongdong Qiao","doi":"10.1016/j.lfs.2025.123718","DOIUrl":"10.1016/j.lfs.2025.123718","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"375 ","pages":"Article 123718"},"PeriodicalIF":5.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143165","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":"Emerging strategies for targeting tumor-associated macrophages in glioblastoma: A focus on chemotaxis blockade","authors":"Chaelin Lee,&nbsp;Jaehyun Lee,&nbsp;Moongyu Jeong,&nbsp;Dayoung Nam,&nbsp;Inmoo Rhee","doi":"10.1016/j.lfs.2025.123762","DOIUrl":"10.1016/j.lfs.2025.123762","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis for affected patients. A key player in the GBM tumor microenvironment is the tumor-associated macrophage (TAM), which promotes tumor progression, immune evasion, and therapeutic resistance. The recruitment of TAMs to the tumor site is driven by specific chemotactic signals, including CSF-1/CSF-1R, CXCR4/CXCL12, and HGF/MET pathways. This review explores the current understanding of these chemotaxis mechanisms and their role in GBM progression. It highlights the potential therapeutic benefits of targeting TAM chemotaxis pathways to disrupt TAM infiltration, reduce immunosuppression, and enhance the efficacy of conventional treatments. Additionally, we discuss the preclinical and clinical evidence surrounding key inhibitors, such as PLX3397, AMD3100, and Crizotinib, which have shown promise in reprogramming TAMs and improving treatment outcomes in GBM. While these strategies offer hope for overcoming some of the challenges of GBM therapy, the review also addresses the limitations and obstacles in clinical translation, emphasizing the need for further research and the development of combination therapies to achieve sustained therapeutic benefit.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123762"},"PeriodicalIF":5.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134945","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}