Molecular and Cellular Biochemistry最新文献

{"title":"Correction to: Clonal hematopoiesis of indeterminate potential: contribution to disease and promising interventions.","authors":"Chongjie Li, Chunxiang Zhang, Xiuying Li","doi":"10.1007/s11010-025-05296-x","DOIUrl":"10.1007/s11010-025-05296-x","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4887"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyocyte-derived Galectin-9 induces macrophage M2 polarization via the TIM3 pathway to attenuate myocardial remodeling post-myocardial infarction.","authors":"Jiabing Huang, Weitong Hu, Hongliang Xiong, Yue Zhou, Fangying Cao, Congcong Ding, Yunde Li, Mingxian Chen","doi":"10.1007/s11010-025-05277-0","DOIUrl":"10.1007/s11010-025-05277-0","url":null,"abstract":"<p><p>M2 macrophages play a key role in tissue repair during the late stages of myocardial infarction (MI). This study highlights the influence of cardiomyocyte-derived Galectin-9 on macrophage function post-MI. Using a murine model with left anterior descending (LAD) artery ligation, we examined the effects of Galectin-9 deficiency, exogenous Galectin-9 supplementation, and macrophage depletion on myocardial macrophage polarization and tissue remodeling. Our results showed increased Galectin-9 expression in infarcted myocardial tissue. Galectin-9 deficiency impaired cardiac recovery and reduced M2 macrophage presence in the infarcted area. Supplementation with exogenous Galectin-9 improved tissue remodeling in Galectin-9-deficient mice and increased M2 macrophage levels. However, macrophage depletion negated the benefits of Galectin-9 supplementation, exacerbating cardiac dysfunction. In vitro, Galectin-9 enhanced the M2 phenotype in macrophage-like RAW264.7 cells after hypoxic preconditioning of cardiomyocytes. This effect was diminished when cardiomyocytes lacked Galectin-9. TIM3 knockdown in RAW264.7 cells reversed the M2 polarization induced by recombinant Galectin-9 and inhibited the PI3K/Akt signaling pathway. These findings suggest that injured cardiomyocytes release Galectin-9 after MI, which binds to TIM3 on macrophages, activating the PI3K/Akt pathway to promote M2 polarization. This cardiomyocyte-macrophage interaction mitigates myocardial remodeling and helps preserve cardiac function after MI.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4809-4827"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of saturated fatty acid metabolism in posttranslational modifications of the Tau protein.","authors":"Valeria Melissa García-Cruz, Roberto Coria, Clorinda Arias","doi":"10.1007/s11010-025-05275-2","DOIUrl":"10.1007/s11010-025-05275-2","url":null,"abstract":"<p><p>The relationship between metabolic alterations induced by the consumption of a high-fat diet (HFD) and the risk of developing neurodegenerative diseases such as Alzheimer's disease (AD) has been extensively studied. In particular, the induction of neuronal insulin resistance, endoplasmic reticulum stress, and the production of reactive oxygen species by chronic exposure to high concentrations of saturated fatty acids (sFAs), such as palmitic acid (PA), have been proposed as the cellular and molecular mechanisms underlying cognitive decline. Lipid metabolism affects many processes critical for cellular homeostasis. However, questions remain as to whether neuronal exposure to high sFA levels contributes to the onset and progression of AD features, and how their metabolism plays a role in this process. Therefore, the aim of this work is to review the accumulated evidence for the potential mechanisms by which the neuronal metabolism of sFAs affects signaling pathways that may induce biochemical changes in the AD hallmark protein Tau, ultimately promoting its aggregation and the subsequent generation of neurofibrillary tangles. In particular, the data presented here provide evidence that PA-dependent metabolic stress results in an imbalance in the activities of protein kinases and deacetylases that potentially contribute to the post-translational modifications (PTMs) of Tau.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4613-4626"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding STING's roles in cancer: immunity, pain, dormancy, and autophagy.","authors":"Huan-Xin Lin, Ya-Ling Tang, Xin-Hua Liang","doi":"10.1007/s11010-025-05281-4","DOIUrl":"10.1007/s11010-025-05281-4","url":null,"abstract":"<p><p>Stimulator of interferon genes (STING) is ubiquitously localized in the endoplasmic reticulum of diverse cell types, serving as a cornerstone of the cyclic GMP-AMP synthase (cGAS)-STING signaling pathway, which is critical for detecting cytosolic DNA and initiating innate immune responses. Conventionally, researchers have characterized STING as a tumor suppressor; however, emerging evidence indicates that activating STING may also facilitate tumor progression. Notably, the tumor-suppressive and tumor-promoting effects mediated by STING are highly context dependent and influenced by specific tumor types and stages. Beyond its central role in immune defense, the STING signaling pathway regulates various physiological and pathological processes within cells. Dormant tumor cells, for instance, can adjust their STING expression to evade immune detection and clearance. Additionally, STING-induced autophagy functions as a negative regulator of STING, establishing a reciprocal interplay that impacts both innate immunity and antitumor immunity. Furthermore, STING activation can simultaneously stimulate the production of proinflammatory and anti-inflammatory cytokines, underscoring its dualistic impact on cancer pain modulation. Therefore, a nuanced understanding of STING's immunoregulatory and alternative roles in antitumor immunity is essential for effectively designing STING-targeted cancer therapies. This review comprehensively analyzes STING's structure and function, systematically elucidating its mechanisms and roles in antitumor immunity, dormancy, autophagy, and cancer pain modulation. By integrating current insights, this work aims to establish a robust theoretical foundation for advancing the development and clinical implementation of STING-targeted cancer therapies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4697-4723"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical and mechanistic perspectives on adipose-derived stem cells for atherosclerotic cardiovascular disease treatment.","authors":"Siarhei A Dabravolski, Mikhail A Popov, Aleksandra S Utkina, Gulalek A Babayeva, Anastasia O Maksaeva, Vasily N Sukhorukov, Alexander N Orekhov","doi":"10.1007/s11010-025-05285-0","DOIUrl":"10.1007/s11010-025-05285-0","url":null,"abstract":"<p><p>Adipose-derived mesenchymal stem cells (AD-MSCs) are a promising therapeutic modality for cardiovascular diseases due to their immunomodulatory, anti-inflammatory, and pro-angiogenic properties. This manuscript explores the current status, challenges, and future directions of AD-MSC therapies, focusing on their application in atherosclerosis (AS), myocardial infarction (MI), and heart failure (HF). Preclinical studies highlight AD-MSC's ability to stabilise atherosclerotic plaques, reduce inflammation, and enhance myocardial repair through mechanisms such as macrophage polarisation, endothelial protection, and angiogenesis. Genetically and pharmacologically modified AD-MSCs, including those overexpressing SIRT1, IGF-1, and PD-L1 or primed with bioactive compounds, exhibit superior efficacy compared to unmodified cells. These modifications enhance cell survival, immunopotency, and reparative capacity, showcasing the potential for tailored therapies. However, clinical translation faces significant hurdles. While recent clinical trials have confirmed the safety of AD-MSC therapy, their efficacy remains inconsistent, necessitating further optimisation of patient selection, dosing strategies, and delivery methods. Donor variability, particularly in patients with co-morbidities like type 2 diabetes (T2D) or obesity, impairs AD-MSC efficacy. Emerging research on extracellular vesicles (EVs) derived from AD-MSC offers a promising cell-free alternative, retaining the therapeutic benefits while mitigating risks. Future perspectives emphasise the need for multidisciplinary approaches to overcome these limitations. Strategies include refining genetic modifications, exploring EV-based therapies, and integrating personalised medicine and advanced diagnostic tools. By addressing these challenges, AD-MSC therapies hold the potential to revolutionise the treatment of cardiovascular diseases, providing innovative solutions to improve patient outcomes.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4647-4670"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Irisin: muscle's novel player in endoplasmic reticulum stress and disease.","authors":"Joel Rimson Pinto, K Deepika Bhat, Bipasha Bose, P Sudheer Shenoy","doi":"10.1007/s11010-025-05272-5","DOIUrl":"10.1007/s11010-025-05272-5","url":null,"abstract":"","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4885-4886"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral nerves-cancer cross-talk: the next frontier in cancer treatment.","authors":"Leihan Wang, Teng Qi, Lingyun Tang, Yuehan Wang, Zhenni ChenLiu, Daorong Wang, Dong Tang","doi":"10.1007/s11010-025-05256-5","DOIUrl":"10.1007/s11010-025-05256-5","url":null,"abstract":"<p><p>The nervous system, which regulates organogenesis, homeostasis, and plasticity of the organism during human growth and development, integrates physiological functions of all organ systems, including the immune system. Its extensive network of branches throughout the body reaches the tumor microenvironment (TME), where it secretes neurotransmitters that directly regulate or influence immune cells. This, in turn, indirectly affects the occurrence, development, and metastasis of cancer. Conversely, cancer cells are now understood to secrete neurotrophic factors that remodel the nervous system. Targeting the cross-talk between the nervous system and cancer represents a promising strategy for cancer treatment, some aspects of which have been confirmed in clinical trials. This review addresses gaps in our understanding of the interaction between peripheral nerves and various human cancers. At the intersection of neuroscience and cancer biology, new targets for neuroscience-based cancer therapies are emerging, establishing a significant new pillar in cancer treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4533-4547"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell and spatial transcriptome analysis reveals the functions of TREM2^high macrophages and infarct border dynamics post-myocardial infarction.","authors":"Tao Xiong, Yan Chen, Chang Liu, Yaxiong Li, Yayong Zhang, Qing Chang","doi":"10.1007/s11010-025-05317-9","DOIUrl":"https://doi.org/10.1007/s11010-025-05317-9","url":null,"abstract":"<p><p>This study employs an integrative approach combining single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and bulk RNA sequencing to investigate the complex cellular and molecular dynamics following myocardial infarction (MI). Quality control, batch correction, dimensionality reduction, clustering, and annotation were performed on scRNA and ST data. The Milo tool was used to analyze differential cell abundance. Developmental trajectory inference was conducted using the Monocle2 algorithm, and cell-cell communication was explored using CellPhoneDB and NicheNet. SCENIC analysis identified active transcription factors (TFs) in macrophage subtypes. Additionally, deconvolution was used to assess the spatial distribution of cell types. The functional roles of different myocardial regions were explored through cell communication patterns. Mouse MI and ischemia-reperfusion (I/R) models were established by ligating the left anterior descending (LAD) coronary artery. Molecular changes were analyzed using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence. In vitro, AC16 cardiomyocytes (CMs) and THP-1-derived M2 macrophages were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and co-culture experiments to study TREM2-mediated effects. Cell viability and apoptosis were assessed using CCK-8 and flow cytometry, respectively. The study identified dynamic changes in the proportions of immune cell types at different time points post-MI. ST revealed distinct immune cell infiltration patterns in the infarct, border, and remote zones, with macrophages progressively infiltrating the infarct region over time. Functional enrichment analysis highlighted key pathways involved in inflammation, cell proliferation, and extracellular matrix remodeling across different cardiac regions. The study also identified Trem2^high macrophages as key players in tissue repair. SCENIC analysis uncovered TFs regulating macrophage subtypes, emphasizing their roles in immune regulation and tissue reconstruction. Finally, cell-cell communication analysis revealed complex signaling networks influencing immune responses and tissue repair. Our results demonstrated that the expressions of Trem2 were significantly increased in the IZ groups in the MI and I/R model, and co-culture with TREM2-overexpressing M2 macrophages significantly enhanced the proliferative capacity and reduced apoptosis in AC16 CMs under OGD/R conditions, indicating a critical role of Trem2 in the I/R response and CMs survival. This comprehensive analysis provides a detailed map of the cellular and molecular landscape post-MI, highlighting the temporal and spatial dynamics of immune cells and their regulatory networks.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2i continuously prevents cardiac hypertrophy by reducing ferroptosis via AMPK up-regulation.","authors":"Bing-Bing Zhao, Jiao Wang, Lu-Lu Zhang, Chao Li, Hong-Hong Xue, Li Zhao, Qing-Hua Han, Hong-Tao Shi","doi":"10.1007/s11010-025-05294-z","DOIUrl":"10.1007/s11010-025-05294-z","url":null,"abstract":"<p><p>Cardiac hypertrophy is an independent risk factor and prognosis indicator of heart failure. Early intervention of cardiac hypertrophy is crucial to prevent heart failure and improve patients' outcomes. Despite evidence that activation of AMPK (adenosine monophosphate-activated protein kinase) plays a protective role in cardiac hypertrophy, whether it plays a sustained role and the precise mechanism remains unexplored. We established in vivo model of cardiac hypertrophy by coarctation of rat abdominal aorta (AAC-CH model). SGLT2 inhibitor (SGLT2i) was used to activate AMPK and cardiac function was evaluated after 2, 4, 8, 12 weeks. Animals were killed, and cardiac tissue was examined for morphological changes, fibrosis, and ferroptosis. At 2 weeks, rats already had histopathological abnormalities including enlarged cardiomyocytes, cardiac fibrosis, and ferroptosis, which persisted overtime. However, these changes were remarkably prevented by the treatment of SGLT2i. Then, we established in vitro model of cardiac hypertrophy by treating H9C2 cells with isoproterenol (ISO,10 µM). Unexpectedly, mechanistic studies revealed that antagonism of AMPK aggravated oxidative stress and ferroptosis, reduced GPX4 (glutathione peroxidase 4) level, and partially abolished the anti-hypertrophic and anti-ferroptosis effects of SGLT2i in H9C2 cells. Taken together, the regulatory role between AMPK and ferroptosis was revealed for the first time in cardiac hypertrophy. SGLT2i counteracts ferroptosis by activating AMPK, providing a sustained protection against cardiac hypertrophy. This positions SGLT2i as a potential therapeutic agent for the treatment of cardiac hypertrophy. Besides, in addition to the downregulation of AMPK in hypertrophic heart tissue, its levels are also reduced in plasma, suggesting its potential to serve as a diagnostic marker for the early detection of ferroptosis and cardiac hypertrophy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4849-4864"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes secreted from adipose-derived stem cells inhibit M1 macrophage polarization ameliorate chronic endometritis by regulating SIRT2/NLRP3.","authors":"Bin Wang, Ruizhu Yu, Zhao Zhang, Yuhong Peng, Li Li","doi":"10.1007/s11010-025-05283-2","DOIUrl":"10.1007/s11010-025-05283-2","url":null,"abstract":"<p><p>Chronic endometritis (CE) is a key factor in adverse pregnancy outcomes such as miscarriage and infertility. Macrophages are an important immune cell type that secrete pro-inflammatory and anti-inflammatory cytokines that are essential for maintaining endometrial function. This study aimed to investigate the key mechanisms by which exosomes derived from adipose-derived mesenchymal stem cells (ADSCs) regulate macrophage polarization through the sirtuin 2 (SIRT2)/NOD-like receptor pyrin containing 3 (NLRP3) axis and exert a protective effect on CE. Exosomes were obtained from ADSCs (ADSCs-exo) using the classical ultracentrifugation method and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. ADSCs-exo protective effects on CE mice and RAW 264.7 cells and its related molecular mechanisms were investigated using real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence, immunoprecipitation, hematoxylin and eosin staining, and immunohistochemistry. ADSCs-exo significantly inhibited M1 macrophage polarization, as evidenced by a 54% reduction in tumor necrosis factor alfa (TNF-α), a 46% reduction in interleukin 1β (IL-1β), and a 36% reduction in interleukin 6 (IL-6) levels in LPS-induced RAW264.7 cells. In vivo, ADSCs-exo treatment reduced the expression of TNF-α by 50%, IL-1β by 58%, and IL-6 by 49% in the uterine tissues of CE mice. Moreover, ADSCs-exo upregulated the expression of SIRT2, promoted the deacetylation modification of NLRP3 to inhibit NLRP3 inflammasome activation, and further suppressed M1 macrophage polarization. However, these trends were reversed after SIRT2 silencing. Our experimental results demonstrate that ADSCs-exo alleviate CE by regulating the SIRT2/NLRP3 axis to inhibit M1 macrophage polarization. This provides a potential theoretical basis for the therapeutic role of stem cells in CE.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4781-4796"},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}