Cellular & Molecular Biology Letters最新文献

{"title":"Autophagy: a double-edged sword in ischemia-reperfusion injury.","authors":"Lingxuan Tang, Wangzheqi Zhang, Yan Liao, Weijie Wang, Xiaoming Deng, Changli Wang, Wenwen Shi","doi":"10.1186/s11658-025-00713-x","DOIUrl":"10.1186/s11658-025-00713-x","url":null,"abstract":"<p><p>Ischemia-reperfusion (I/R) injury describes the pathological process wherein tissue damage, initially caused by insufficient blood supply (ischemia), is exacerbated upon the restoration of blood flow (reperfusion). This phenomenon can lead to irreversible tissue damage and is commonly observed in contexts such as cardiac surgery and stroke, where blood supply is temporarily obstructed. During ischemic conditions, the anaerobic metabolism of tissues and organs results in compromised enzyme activity. Subsequent reperfusion exacerbates mitochondrial dysfunction, leading to increased oxidative stress and the accumulation of reactive oxygen species (ROS). This cascade ultimately triggers cell death through mechanisms such as autophagy and mitophagy. Autophagy constitutes a crucial catabolic mechanism within eukaryotic cells, facilitating the degradation and recycling of damaged, aged, or superfluous organelles and proteins via the lysosomal pathway. This process is essential for maintaining cellular homeostasis and adapting to diverse stress conditions. As a cellular self-degradation and clearance mechanism, autophagy exhibits a dualistic function: it can confer protection during the initial phases of cellular injury, yet potentially exacerbate damage in the later stages. This paper aims to elucidate the fundamental mechanisms of autophagy in I/R injury, highlighting its dual role in regulation and its effects on both organ-specific and systemic responses. By comprehending the dual mechanisms of autophagy and their implications for organ function, this study seeks to explore the potential for therapeutic interventions through the modulation of autophagy within clinical settings.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"42"},"PeriodicalIF":9.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicle-stimulating hormone promotes EndMT in endothelial cells by upregulating ALKBH5 expression.","authors":"Ping Li, Yixiao Xiang, Jinzhi Wei, Xingyan Xu, Jiale Wang, Haowei Yu, Xiaosa Li, Huiping Lin, Xiaodong Fu","doi":"10.1186/s11658-025-00720-y","DOIUrl":"10.1186/s11658-025-00720-y","url":null,"abstract":"<p><strong>Background: </strong>The incidence of atherosclerosis markedly rises following menopause. Our previous findings demonstrated that elevated follicle-stimulating hormone (FSH) levels in postmenopausal women accelerate atherosclerosis progression. Plaque instability, the fundamental pathological factor in acute coronary syndrome, primarily results from vascular embolism due to plaque rupture. Recent evidence highlights that endothelial-to-mesenchymal transition (EndMT) exacerbates plaque instability, although the link between FSH and EndMT has not been fully established. This investigation sought to explore the possible influence of FSH in modulating EndMT.</p><p><strong>Methods: </strong>In this study, apolipoprotein E-deficient (ApoE^-/-) mice served as an atherosclerosis model, while human umbilical vascular endothelial cells (HUVECs) were used as cellular models. Protein levels were assessed through immunochemical techniques, gene expression was quantified via RT-qPCR, and nucleic acid-protein interactions were evaluated using immunoprecipitation. The m6A modification status was determined by MeRIP, and cellular behaviors were analyzed through standard biochemical assays.</p><p><strong>Results: </strong>Our results indicate that FSH induces EndMT both in vitro and in vivo. Additional investigation suggested that FSH upregulates the transcription factor Forkhead box protein M1 (FOXM1) at both protein and mRNA levels by enhancing the expression of AlkB homolog 5, RNA demethylase (ALKBH5). FSH reduces m6A modifications on FOXM1 through ALKBH5, leading to increased nascent transcript levels and mRNA stability of FOXM1. Dual-luciferase reporter assays highlighted cAMP-response element binding protein (CREB)'s essential function in facilitating the FSH-induced upregulation of ALKBH5.</p><p><strong>Conclusions: </strong>These findings suggest that FSH promotes ALKBH5 expression, facilitates N⁶-methyladenosine (m6A) demethylation on FOXM1, and consequently, induces EndMT. This study elucidates the impact of FSH on plaque instability and provides insights into potential strategies to prevent acute coronary syndrome in postmenopausal women.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"41"},"PeriodicalIF":9.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mechanism for A-to-I RNA-edited CYP1A1 in promoting cancer progression in NSCLC.","authors":"Zhipeng Wang, Yan Wu, Ziqi Ding, Xinru Xiao, Yanhua Huang, Zhiguang Liu, Qian Zhang","doi":"10.1186/s11658-025-00718-6","DOIUrl":"10.1186/s11658-025-00718-6","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related mortality worldwide. Similar to other solid tumors, the development of non-small cell lung cancer (NSCLC) is believed to be a multistep process involving the accumulation of genetic and epigenetic alterations. A-to-I RNA editing is a widespread posttranscriptional epigenetic modification that confers specific nucleotide changes in selected RNA transcripts and plays a critical role in the pathogenesis of many human cancers. However, the mechanisms underlying A-to-I RNA editing that act as a potential driver in the pathogenesis of NSCLC progression remain incompletely elucidated.</p><p><strong>Methods: </strong>Sanger sequencing was performed to validate the CYP1A1_I462V RNA editing event in NSCLC patients. In vitro and in vivo experiments were used to assess the effects of an ADAR1-regulated CYP1A1 and its editing on NSCLC cell growth and metastasis. The crosstalk between CYP1A1_I462V RNA editing and PI3K-AKT signaling was analyzed using RNA sequencing and molecular methods. The functional role of CYP1A1_I462V in the response to oxidative stress was verified through proteomics analysis, co-IP assay, and immunofluorescence assay.</p><p><strong>Results: </strong>Sanger sequencing analysis identified an increased A-to-I RNA editing ratio of CYP1A1 in NSCLC specimens. This specific RNA editing, regulated by ADAR1, resulted in gain-of-function phenotypes characterized by enhanced tumor progression and more aggressive behavior. The edited form induced the expression of heme oxygenase-1 (HO-1) via PI3K/Akt-dependent activation compared with the wild-type CYP1A1, which led to an enhanced interaction with CYP1A1, thereby promoting the translocation of abundant HO-1 into the nucleus to resist oxidant stress in NSCLC cells.</p><p><strong>Conclusions: </strong>Our findings highlight that the I462V A-to-I RNA editing event of CYP1A1 drives pulmonary carcinogenesis through inhibiting oxidative stress and suggest that the CYP1A1-HO-1-PI3K/Akt axis may be a potential therapeutic target for NSCLC.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"40"},"PeriodicalIF":9.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAFF alleviates hepatic ischemia-reperfusion injury by regulating the CLCF1/STAT3 signaling pathway.","authors":"Dengliang Lei, Yihua Wang, Shanshan Li, Song Xiang, Yunhai Luo, Ping Yan, Fang Luo, Zuotian Huang, ZhongJun Wu","doi":"10.1186/s11658-025-00721-x","DOIUrl":"10.1186/s11658-025-00721-x","url":null,"abstract":"<p><strong>Background: </strong>Although hepatic ischemia-reperfusion injury (IRI) frequently occurs during liver resection and transplantation, the underlying mechanisms remain incompletely understood. Through high-throughput sequencing, we found that v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) expression was significantly increased after hepatic IRI. The specific role of MAFF, a basic leucine zipper (bZIP) transcription factor, in hepatic IRI is unknown. In the present study, we aimed to explore the effect of MAFF on hepatic IRI injury.</p><p><strong>Approach and results: </strong>Adenovirus vectors carrying the MAFF gene were administered to mice to explore the potential significance of MAFF. After ischemia-reperfusion, MAFF expression was significantly upregulated, suggesting a potential association between MAFF expression and hepatocyte apoptosis. A reduction in MAFF expression was demonstrated to worsen hepatic impairment and enhance the expression of proinflammatory cytokines in mice following ischemia-reperfusion. Conversely, MAFF overexpression had the opposite effect. Mechanistically, the combination of CUT&Tag and RNA sequencing technologies identified cardiotrophic factor-like cytokine 1 (CLCF1) as a direct transcriptional target for MAFF and BTB and CNC homology 1 (BACH1) heterodimers. This interaction subsequently triggers signal transducer and activator of transcription 3 (STAT3) signaling.</p><p><strong>Conclusions: </strong>MAFF alleviates hepatic ischemia-reperfusion injury by reducing hepatocyte apoptosis and the inflammatory response through the activation of the CLCF1/STAT3 signaling pathway, offering valuable insights into the impact of MAFF on liver protection and potential therapeutic targets for liver treatment.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"39"},"PeriodicalIF":9.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel regulation mechanism of histone methyltransferase SMYD5 in rheumatoid arthritis.","authors":"Chenxi Xiao, Zhenghua Su, Jialin Zhao, Subei Tan, Mengting He, Yuhui Li, Jiayao Liu, Jie Xu, Yajie Hu, Zhongzheng Li, Chunxiang Fan, Xinhua Liu","doi":"10.1186/s11658-025-00707-9","DOIUrl":"10.1186/s11658-025-00707-9","url":null,"abstract":"<p><strong>Background: </strong>Fibroblast-like synoviocytes (FLS) are crucial for maintaining synovial homeostasis. SMYD5, a member of the histone lysine methyltransferase subfamily SMYDs, is involved in many pathological processes. This study aimed to investigate the role of SMYD5 in regulating synovial fibroblast homeostasis and the pathogenesis of rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>Proteomic screening was conducted to assess SMYD5 expression in the synovium of patients with osteoarthritis (OA) and RA. In vitro, interleukin-1 beta (IL-1β) was used to induce proliferation and inflammation in FLS. Further, we performed loss-of-function and gain-of-function experiments to investigate the biological function of SMYD5. In vivo, adeno-associated virus (AAV) vectors carrying SMYD5 short-hairpin RNA (AAV-shSMYD5) were injected into the knee joints to knock down SMYD5 in a collagen-induced arthritis (CIA) mouse model to evaluate its role in joint damage.</p><p><strong>Results: </strong>We observed a significant elevation of SMYD5 expression in the synovial tissues of patients with RA and IL-1β-induced FLS. SMYD5 facilitated posttranslational modifications and activated downstream signaling pathways, thereby promoting proliferation and inflammation in FLS. Mechanistically, SMYD5 mediated the methylation of Forkhead box protein O1 (FoxO1), which accelerated its degradation through ubiquitination, resulting in substantial FLS proliferation. Additionally, SMYD5 promoted lactate release to activate NF-κB signaling pathways by upregulating hexokinases-2 (HK2) expression, a key glycolytic enzyme, thereby intensifying the inflammatory response in FLS. Supporting these findings, intraarticular delivery of AAV-mediated SMYD5 knockdown in the CIA mice model effectively alleviated joint swelling, bone erosion, and overall arthritis severity.</p><p><strong>Conclusions: </strong>Together, these findings suggest that SMYD5 is a dual target for regulating synovial fibroblast homeostasis and the pathogenesis of RA. Targeting SMYD5 through local treatment strategies may provide a novel therapeutic approach for RA, particularly when combined with immunotherapy.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"38"},"PeriodicalIF":9.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircNF1 modulates the progression and immune evasion of esophageal squamous cell carcinoma through dual regulation of PD-L1.","authors":"Chang Wang, Chenxi Ju, Dan Du, Peiyu Zhu, Jie Yin, Jinlin Jia, Xue Wang, Xinyu Xu, Li Zhao, Junhu Wan, Ting Sun, Lijun Yang, Hongle Li, Fucheng He, Mingxia Zhou, Jing He","doi":"10.1186/s11658-025-00712-y","DOIUrl":"10.1186/s11658-025-00712-y","url":null,"abstract":"<p><strong>Background: </strong>Tumor immune escape is a pivotal gateway for esophageal squamous cell carcinoma (ESCC) development. Immune checkpoint-blocking therapies, represented by programmed cell death receptor-1/ligand 1 (PD-1/PD-L1) inhibitors, have achieved remarkable breakthroughs in ESCC treatment. However, not all patients with ESCC receive satisfactory clinical benefit. Therefore, identifying novel biomarkers for predicting the efficacy of immunotherapy in ESCC is of great importance.</p><p><strong>Methods: </strong>CircNF1 was screened from the circRNAs microarray, and its expression was measured by droplet digital polymerase chain reaction (ddPCR) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in ESCC tissues and serum. Functional experiments were conducted to demonstrate the role of circNF1 in ESCC proliferation, metastasis, and tumor evasion. High-throughput RNA sequencing, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), and chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) were performed to clarify the underlying mechanisms of circNF1-mediated tumor progression.</p><p><strong>Results: </strong>The upregulation of circNF1 was closely associated with the response of anti-PD-L1 immunotherapy. Functionally, circNF1 promoted ESCC cell malignant phenotypes and regulated CD8⁺ T-cell-mediated antitumor immunity. Mechanistically, circNF1 drove the IL-6-induced oncogenic activation of the JAK-STAT3 pathway, which stimulated p-STAT3 binding of the promoter regions of PD-L1. Furthermore, circNF1 physically interacted with annexin A1 (ANXA1), blocking the ANXA1 deubiquitination induced by ubiquitin-specific protease 7 (USP7), resulting in increased interaction between USP7 and PD-L1 and augmented PD-L1 stability.</p><p><strong>Conclusions: </strong>Our findings provide novel insights into the specific regulatory mechanism of PD-L1 in ESCC cells, which offer a new strategy for synergizing with anti-PD-L1 therapy.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"37"},"PeriodicalIF":9.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and epigenetic regulation of Treg cell fitness by autism-related chromatin remodeler CHD8.","authors":"Jun-Qi Yang, Chen Wang, Ramesh C Nayak, Manohar Kolla, Mingjun Cai, Mario Pujato, Yi Zheng, Q Richard Lu, Fukun Guo","doi":"10.1186/s11658-025-00711-z","DOIUrl":"https://doi.org/10.1186/s11658-025-00711-z","url":null,"abstract":"<p><strong>Background: </strong>Chromatin remodeler chromodomain helicase DNA-binding protein 8 (CHD8) defines a subtype of autism that is associated with immune disorders. It remains unknown whether CHD8 plays a cell-intrinsic role in immune cells such as regulatory T cells (Tregs) that maintain immune tolerance through suppressing CD4⁺ and CD8⁺ effector T cells.</p><p><strong>Methods: </strong>Treg-specific conditional CHD8-deficient mice were generated by crossing Chd8^Flox/Flox mice with Foxp3^YFP-cre transgenic mice. Effects of CHD8 deficiency were investigated using hematoxylin and eosin (H&E) staining, flow cytometry, and multi-omics, including RNA-sequencing (RNA-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (CHIP-seq).</p><p><strong>Results: </strong>We found that Treg-specific CHD8 deletion led to early, fatal inflammation owing to increased CD4⁺ and CD8⁺ effector T cells. CHD8 deletion did not alter Treg homeostasis but increased their functional plasticity with elevated expression of effector T cell cytokines. CHIP-seq of Tregs uncovered that CHD8 binding genes were enriched in phosphatidylinositol-3 kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling and several other pathways. RNA-seq and ATAC-seq revealed that CHD8 deletion upregulated a number of pathways, notably mammalian target of rapamycin complex 1 (mTORC1) signaling and its mediated glycolysis that have been reported to promote Treg plasticity. Integrating RNA-seq data with CHIP-seq and ATAC-seq data identified a number of CHD8 target genes whose expression depends on CHD8 direct binding-mediated chromatin remodeling.</p><p><strong>Conclusions: </strong>Our findings suggest that CHD8 plays an important role in maintaining Treg fitness through genetic and epigenetic mechanisms to control autoimmunity, which may have important implications in immune changes in autism.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"36"},"PeriodicalIF":9.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.","authors":"A Anjana Mohan, Priti Talwar","doi":"10.1186/s11658-025-00714-w","DOIUrl":"10.1186/s11658-025-00714-w","url":null,"abstract":"<p><p>Mitochondria-associated membranes (MAMs) are tethering regions amid the membranes of the endoplasmic reticulum (ER) and mitochondria. They are a lipid raft-like structure occupied by various proteins that facilitates signal transduction between the two organelles. The MAM proteome participates in cellular functions such as calcium (Ca²⁺) homeostasis, lipid synthesis, ER stress, inflammation, autophagy, mitophagy, and apoptosis. The human kinome is a superfamily of homologous proteins consisting of 538 kinases. MAM-associated kinases participate in the aforementioned cellular functions and act as cell fate executors. Studies have proved the dysregulated kinase interactions in MAM as an etiology for various diseases including cancer, diabetes mellitus, neurodegenerative diseases, cardiovascular diseases (CVDs), and obesity. Several small kinase inhibitory molecules have been well explored as promising drug candidates in clinical trials with an accelerating impact in the field of precision medicine. This review narrates the physiological actions, pathophysiology, and therapeutic potential of MAM-associated kinases with recent updates in the field.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"35"},"PeriodicalIF":9.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the roles of macrophages in Klebsiella pneumoniae infections: a comprehensive review.","authors":"Yangguang Li, Xuanheng Li, Wenqi Wu, Peizhao Liu, Juanhan Liu, Haiyang Jiang, Liting Deng, Chujun Ni, Xiuwen Wu, Yun Zhao, Jianan Ren","doi":"10.1186/s11658-025-00717-7","DOIUrl":"10.1186/s11658-025-00717-7","url":null,"abstract":"<p><p>Klebsiella pneumoniae (KP) infections represent a significant global health challenge, characterized by severe inflammatory sequelae and escalating antimicrobial resistance. This comprehensive review elucidates the complex interplay between macrophages and KP, encompassing pathogen recognition mechanisms, macrophage activation states, cellular death pathways, and emerging immunotherapeutic strategies. We critically analyze current literature on macrophage pattern recognition receptor engagement with KP-associated molecular patterns. The review examines the spectrum of macrophage responses to KP infection, including classical M1 polarization and the newly described M(Kp) phenotype, alongside metabolic reprogramming events such as glycolytic enhancement and immune responsive gene 1 (IRG1)-itaconate upregulation. We systematically evaluate macrophage fate decisions in response to KP, including autophagy, apoptosis, pyroptosis, and necroptosis. Furthermore, we provide a critical assessment of potential future therapeutic modalities. Given the limitations of current treatment paradigms, elucidating macrophage-KP interactions is imperative. Insights gained from this analysis may inform the development of novel immunomodulatory approaches to augment conventional antimicrobial therapies, potentially transforming the clinical management of KP infections.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"34"},"PeriodicalIF":9.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The exosome collection.","authors":"Steven R Goodman","doi":"10.1186/s11658-025-00719-5","DOIUrl":"10.1186/s11658-025-00719-5","url":null,"abstract":"","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"33"},"PeriodicalIF":9.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}