Frontiers in bioscience (Landmark edition)最新文献

{"title":"LONP1 Promotes Hepatocarcinogenesis by Degrading ACO2 to Alleviate Ferroptosis.","authors":"Yanfeng Zhong, Liusheng Wu, Zhen Peng, Wei Mao, Ting Wang, Bo Wu, Zhendong Yu, Xiaoqiang Li, Erbao Chen","doi":"10.31083/FBL41226","DOIUrl":"https://doi.org/10.31083/FBL41226","url":null,"abstract":"<p><strong>Background: </strong>Lon protease 1 (LONP1), an adenosine triphosphate (ATP)-dependent protease encoded by nuclear DNA that is highly conserved, maintains the mitochondrial protein balance and regulates adaptive responses to cellular stress. LONP1 dysfunction ultimately results in various forms of cellular and tissue damage. The function of LONP1 in hepatocellular carcinoma (HCC) and how it affects HCC growth were investigated in this work.</p><p><strong>Methods: </strong>The RNA and protein expression levels of LONP1 were determined in paired HCC and adjacent tissue samples through real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) staining. The correlation between LONP1 expression and clinical features was evaluated via statistical analysis. Overexpression (OE) and knockdown (KD) experiments, small RNA interference, Cell Counting Kit-8 (CCK8) and wound-healing assays, and animal experiments were employed to assess the potential mechanism by which LONP1 promotes the proliferation and migration of HCC cells both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>In HCC samples, LONP1 expression was higher than in the equivalent surrounding tissues. Compared to patients with low LONP1 expression, individuals with high LONP1 expression had shorter disease-free survival and overall survival periods. Functionally, LONP1 facilitated the proliferation and migration of HCC cells, whereas LONP1 knockdown mitigated the growth of HCC subcutaneous tumors. Mechanistically, LONP1 affects the processes of ferroptosis and cuproptosis processes by regulating the stability of aconitase 2 (ACO2). Histological analysis showed that the expression of LONP1 in liver cancer tissues was significantly upregulated, accompanied by a decrease in the level of ACO2 protein (Hematoxylin-Eosin (HE) staining and IHC verification). Mitochondrial function experiments indicated that overexpression of LONP1 led to a significant decrease in mitochondrial membrane potential suggesting mitochondrial dysfunction and reduced susceptibility to ferroptosis.</p><p><strong>Conclusions: </strong>Our results suggest that LONP1 promotes HCC proliferation and migration by inhibiting ferroptosis and cuproptosis through the degradation of ACO2. Therefore, targeting LONP1 might be an effective therapeutic strategy to inhibit HCC growth.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"41226"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AURKA Suppresses Ferroptosis via the KEAP1/NRF2/HO‑1 Axis in EGFR-Mutant Lung Adenocarcinoma.","authors":"Yufeng Huang, Gengqiu Liu, Zhu Liang, Junhang Zhang","doi":"10.31083/FBL41293","DOIUrl":"https://doi.org/10.31083/FBL41293","url":null,"abstract":"<p><strong>Background: </strong>Adenocarcinoma of Lung (LUAD) remains a leading cause of cancer-related deaths across the globe, and patients harboring epidermal growth factor receptor (EGFR) mutations frequently develop resistance to targeted therapies. While aurora kinase A (AURKA) has been implicated in tumorigenesis, its involvement in regulating ferroptosis via the kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2)/heme oxygenase 1 (HO‑1) signaling axis in EGFR-mutant LUAD remains poorly understood.</p><p><strong>Methods: </strong>We analyzed RNA-seq and clinical data from 594 LUAD samples from The Cancer Genome Atlas (TCGA) to explore associations between AURKA expression, EGFR mutation status, and immune cell infiltration. A ferroptosis-focused random forest algorithm was constructed to predict EGFR-mutant cases. <i>In vitro</i>, AURKA was silenced by siRNA in EGFR-mutant NCI-H1975 cells; subsequent assays included transcriptome profiling, measurements of intracellular Fe²⁺, malondialdehyde (MDA), glutathione (GSH), mitochondrial reactive oxygen species (ROS) levels, and ultrastructural examination by electron microscopy. Protein levels of NRF2, HO‑1, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and KEAP1 were assessed via western blot.</p><p><strong>Results: </strong>The ferroptosis gene-based random forest model distinguished EGFR-mutant LUAD with an area under the curve (AUC) of 0.84. Clinically, high AURKA expression was significantly associated with EGFR wild-type status (<i>p</i> = 0.035), reduced overall survival (<i>p</i> = 0.011), increased M1 macrophage infiltration, and decreased CD4⁺ T-cell infiltration. AURKA knockdown triggered hallmark features of ferroptosis-iron overload (<i>p</i> < 0.001), elevated MDA levels (<i>p</i> < 0.01), increased lipid peroxidation (<i>p</i> < 0.05), heightened mitochondrial ROS (<i>p</i> < 0.05), reduced mitochondrial membrane potential, GSH depletion (<i>p </i><<i> </i>0.05), and disruption of mitochondrial cristae. Mechanistically, loss of AURKA decreased KEAP1 (<i>p</i> < 0.01) and enhanced NRF2 (<i>p</i> < 0.001) and HO-1 (<i>p</i> < 0.01) and NRF2 nuclear translocation, while downregulating SLC7A11 (<i>p</i> < 0.05) and GPX4 (<i>p</i> < 0.01). Cell cycle analysis revealed G1-phase arrest (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>Our findings demonstrate that AURKA promotes ferroptosis resistance in EGFR-mutant LUAD by modulating the KEAP1/NRF2/HO-1 axis. Notably, this effect was validated in the gefitinib-resistant EGFR T790M-mutant NCI-H1975 cell model. Our results highlight AURKA as a potential therapeutic target for overcoming epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and suggest that disrupting the AURKA/KEAP1/NRF2/HO‑1 pathway may offer a novel strategy for treating EGFR-mutant LUAD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"41293"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Mechanism Connecting Preeclampsia to Autism Spectrum Disorder in Offspring: The Role of Microglial Abnormalities.","authors":"Ying Zhu, Si-Yi Wei, Xiao-Tong Fu, Xi Cheng, Xian-Hua Lin","doi":"10.31083/FBL36412","DOIUrl":"10.31083/FBL36412","url":null,"abstract":"<p><p>Preeclampsia (PE) is a serious complication of pregnancy characterized by chronic inflammation and immune dysregulation, which significantly increases the risk of neurodevelopmental disorders in offspring, including the autism spectrum disorder (ASD). This review investigated the potential mechanisms linking PE to ASD, with a particular focus on the role of microglial abnormalities. Epidemiological studies have revealed that prenatal exposure to PE raised the risk of ASD, with affected offspring showing increased odds ratios. Microglia, the prime resident immune cells of the central nervous system (CNS), are critical for normal neurodevelopment, influencing processes such as neural stem cell (NSC) proliferation, synaptic pruning, and normal function of the neural circuit. Early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) may have an impact on the microglia abnormality and ASD through not exactly same pathway. Postmortem studies of ASD have further revealed increased microglial density, altered microglial morphology, and upregulated inflammatory markers in key brain regions, including the hippocampus and prefrontal cortex. Understanding the complex processes and potential mechanisms between EOPE, LOPE, microglial abnormalities, and ASD pathogenesis may highlight the importance of early screening and intervention for children born to mothers with PE. Targeting microglia-mediated pathways may offer novel therapeutic strategies to reduce the risk of ASD in these vulnerable populations.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"36412"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Pathogenesis of Sarcopenia: Regulatory Networks Involving MicroRNAs in Age-Related Skeletal Muscle Decline.","authors":"Joseph Joju Kalan, Lijo N Varghese, Rajesh Katare","doi":"10.31083/FBL38106","DOIUrl":"https://doi.org/10.31083/FBL38106","url":null,"abstract":"<p><p>Sarcopenia is the progressive loss of skeletal muscle mass, strength, and function, significantly contributing to frailty, disability, and mortality in aging populations. As life expectancy rises, sarcopenia presents a growing public health challenge, increasing healthcare costs, and diminishing quality of life. Despite its prevalence, sarcopenia is often underdiagnosed due to limitations in current diagnostic tools, including the lack of standardized cut-off values and reliance on physical performance tests. The causes of sarcopenia are multifactorial, involving oxidative stress, chronic inflammation, mitochondrial dysfunction, satellite cell depletion, and impaired angiogenesis. Recent research highlights the role of microRNAs (miRs) in regulating these molecular pathways. miRs influence muscle homeostasis by modulating gene expression related to muscle atrophy, apoptosis, inflammation, and insulin resistance. While non-pharmacological interventions such as resistance training and blood flow restriction therapy remain the primary treatment strategies, their effectiveness is often limited in older adults with reduced muscle regenerative capacity. The identification of miRs as biomarkers could enhance early diagnosis and enable more personalized treatment approaches. However, further research is required to validate their clinical utility and therapeutic potential. This review comprehensively analyses the molecular mechanisms underlying sarcopenia, current diagnostic challenges, and emerging miR-based strategies that could transform its management. Future efforts should focus on integrating these molecular insights into clinical practice to improve early detection and intervention strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"38106"},"PeriodicalIF":3.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy.","authors":"Li-Min Mao, Elizabeth Puthumana, John Q Wang","doi":"10.31083/FBL26637","DOIUrl":"10.31083/FBL26637","url":null,"abstract":"<p><p>Glutamate is an important neurotransmitter in the mammalian brain. Among the receptors that glutamate interacts with is metabotropic glutamate (mGlu) receptor 2, a Gα_i/o-coupled receptor. These receptors are primarily located on glutamatergic nerve terminals and act as presynaptic autoreceptors to produce feedback inhibition of glutamate release. Abundant mGlu2 receptors are distributed in major glutamatergic pathways in the basal ganglia, especially the corticostriatal and thalamostriatal projections in the striatum. These receptors are involved in the regulation of motivation, reward processing, learning, motor, and cognitive functions. As an inhibitory presynaptic receptor, mGlu2 is linked to the addictive properties of drugs of abuse, a topic summarized in this review. Chronic exposure to multiple addictive drugs and alcohol causes the adaptive downregulation of mGlu2 receptors in their expression and function in the key regions of the limbic reward circuit. This downregulation contributes to the remodeling of limbic excitatory synaptic transmission and plasticity critical for enduring drug-seeking behavior. Normalization of mGlu2 activity by pharmacological or genetic approaches attenuates drug taking and seeking. Here, we highlight that recent progress in mGlu2 biology research demonstrates the pivotal roles of mGlu2 receptors in different aspects of drug addiction. mGlu2 subtype-selective agents (both orthosteric and allosteric compounds) thus have the potential to be developed into novel pharmacotherapies for addictive conditions.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"26637"},"PeriodicalIF":3.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Phospholipids in Mitochondrial Dynamics and Associated Diseases.","authors":"Solenn Plouzennec, Juan Manuel Chao de la Barca, Arnaud Chevrollier","doi":"10.31083/FBL27634","DOIUrl":"https://doi.org/10.31083/FBL27634","url":null,"abstract":"<p><p>The bioenergetic machinery of the cell is protected and structured within two layers of mitochondrial membranes. The mitochondrial inner membrane is extremely rich in proteins, including respiratory chain complexes, substrate transport proteins, ion exchangers, and structural fusion proteins. These proteins participate directly or indirectly in shaping the membrane's curvature and facilitating its folding, as well as promoting the formation of nanotubes, and proton-rich pockets known as cristae. Recent fluorescent super-resolution images have demonstrated the strong dynamics of these events, with constant remodeling processes. The mitochondrial outer membrane itself is also highly dynamic, interacting with the endoplasmic reticulum and its environment to ensure a rapid diffusion of surface components throughout the mitochondrial networks. All these movements occur besides migration, fusion, and fission of the mitochondria themselves. These dynamic events at the level of mitochondrial membranes are primarily dependent on their unique lipid composition. In this review, we discuss the latest advances in phospholipid research, focusing on their metabolism and role in mitochondrial dynamics. This process emphasizes the importance of interactions with the endoplasmic reticulum and mitochondrial matrix enzymes, extending its relevance to lipid sources, in particular, cardiolipins and phosphatidylethanolamines at the cellular, tissue and even whole-organism level. Given the expanding array of characterized mitochondrial functions, ranging from calcium homeostasis to inflammation and cellular senescence, research in the field of mitochondrial lipids is particularly significant. As mitochondria play a central role in various pathological processes, including cancer and neurodegenerative disorders, lipid metabolism may offer promising therapeutic approaches.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"27634"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Immunological, and Vesicular Markers in Sarcopenia and Presarcopenia.","authors":"Liudmila M Shuliko, Dmitry A Svarovsky, Liudmila V Spirina, Ikponmwosa Jude Ogieuhi, Olga E Akbasheva, Mariia V Matveeva, Iuliia G Samoilova, Valeria A Shokalo, Sofia S Timoshenko, Sofia M Merkulova, Amin I Ragimov, Mar'yam P Shukyurova, Natalia V Tarasenko","doi":"10.31083/FBL42063","DOIUrl":"https://doi.org/10.31083/FBL42063","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sarcopenia is a complex, multifactorial condition characterized by progressive loss of muscle mass, strength, and function. Despite growing awareness, the early diagnosis and pathophysiological characterization of this condition remain challenging due to the lack of integrative biomarkers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to conduct a comprehensive multilevel profiling of clinical parameters, immune cell phenotypes, extracellular vesicle (EV) signatures, and biochemical markers to elucidate biological gradients associated with different stages of sarcopenia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;A prospective cohort study enrolled adults aged 45-85 years classified as control, presarcopenic, or sarcopenic based on European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Clinical evaluation included anthropometry, muscle strength, sarcopenia screening (SARC-F) questionnaire/Short Physical Performance Battery (SPPB) questionnaires, and quality-of-life assessment. Flow cytometry was used to characterize blood monocyte/macrophage subsets (cluster of differentiation 14 (CD14), CD68, CD163, CD206). EVs were isolated from plasma and profiled for surface tetraspanins and matrix metalloproteinases (MMP2, MMP9, tissue inhibitor of metalloproteinase-1 (TIMP-1)) using bead-based flow cytometry. Biochemical assays measured metabolic, inflammatory, and extracellular matrix (ECM)-related markers. Data were analyzed via Kruskal-Wallis testing, discriminant analysis, and principal component analysis (PCA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sarcopenia, a muscle-wasting condition linked to aging, is characterized by chronic inflammation, proteolytic imbalance, and metabolic disturbances. Clinical deterioration is evident through reduced appendicular lean mass (ALM), appendicular skeletal muscle index (ASMI), SPPB scores, and sarcopenia quality of life (SarQoL) domains. Principal component analysis (PCA) identified four functional marker clusters: ECM degradation (MMP-positive EVs), inflammatory and homeostasis-stabilizing macrophages, and metabolic disruption (glucose, asprosin, triglycerides). Discriminant analysis emphasized vesicular and immune markers with significant classification potential, even when univariate differences were non-significant. Metabolic destabilization and inflammatory activation are detectable in presarcopenia stages. Chronic inflammation, characterized by CD14-CD163+206+ cells releasing pro-inflammatory cytokines, accelerates muscle degradation. Proteolytic dysfunction, with an imbalance between proteases and inhibitors, further contributes to muscle loss. Metabolic disorders impair energy production and nutrient utilization, exacerbating muscle wasting. A comprehensive assessment, including anthropometric, functional, physical activity, and QoL measures, is crucial for identifying high-risk individuals and understanding sarcopenia's mechanisms. Vesicular biomarkers","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"42063"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functions and Mechanisms of Diabetes-Linked Transcription Factors.","authors":"Naveen K Parthiban, Najah T Nassif, Ann M Simpson","doi":"10.31083/FBL36544","DOIUrl":"https://doi.org/10.31083/FBL36544","url":null,"abstract":"<p><p>Transcription factors are significant regulators of gene expression in most biological processes related to diabetes, including beta cell (β-cell) development, insulin secretion and glucose metabolism. Dysregulation of transcription factor expression or abundance has been closely associated with the pathogenesis of type 1 and type 2 diabetes, including pancreatic and duodenal homeobox 1 (<i>PDX1</i>), neurogenic differentiation 1 (<i>NEUROD1</i>), and forkhead box protein O1 (<i>FOXO1</i>). Gene expression is regulated at the transcriptional level by transcription factor binding, epigenetically by DNA methylation and chromatin remodelling, and post-transcriptional mechanisms, including alternative splicing and microRNA (miRNA). Recent data indicate a central role for transcription factors in pancreatic β-cell failure in the context of systemic insulin resistance and chronic inflammation. Therapeutic modulation of transcription factor abundance via gene therapy, small-molecule pharmacology, and epigenetic therapies holds great promise for β-cell restoration and metabolic normalisation. However, further clinical translation will require targeted delivery to appropriate tissues, minimising off-target effects and ensuring long-term safety. This review focuses on the involvement of pancreatic β-cells and transcription factors in diabetes development and their therapeutic implications, intending to develop and consolidate a basis for further research in this area and for the treatment of diabetes in the future.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"36544"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Galectin-3 Expression Could Preserve the Immunoregulatory Function of Mesenchymal Stem Cells During Cell Passaging.","authors":"Minghui Wang, Yan Jiang, Jiangbo Wan, Difan Zhang, Fang Huang, Siguo Hao","doi":"10.31083/FBL39918","DOIUrl":"https://doi.org/10.31083/FBL39918","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are one of the effective treatments for acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to their potent immunoregulatory function. Given the limited quantity and high heterogeneity of freshly isolated MSCs, extensive <i>in vitro</i> expansion is essential for clinical application. Prolonged passaging of MSCs leads to a decline in therapeutic efficacy, with the underlying mechanisms remaining unclear. This study aimed to explore the mechanism and intervention strategies of immunoregulatory dysfunction of MSCs during passaging.</p><p><strong>Methods: </strong>We compared the therapeutic effects of MSCs at early passages (passage 6, P6-MSCs) and later passages (passage 12, P12-MSCs) in a mouse GVHD model. We also analyzed the expression of Gal-3 in MSCs at different passages and its role in macrophage polarization. Additionally, the selective Gal-3 inhibitor TD139 was evaluated for its effects on Gal-3 expression and the immunoregulatory function of MSCs.</p><p><strong>Results: </strong>Our data showed an inverse correlation between passage number and therapeutic efficacy in MSCs. Late-passage MSCs (P12) exhibited significantly reduced efficacy in alleviating GVHD compared to early-passage MSCs (P6). The expression of Gal-3 was markedly upregulated in late-passage MSCs (P12), and it was found to directly inhibit anti-inflammatory M2-like macrophage polarization. Our research demonstrated that TD139 dose-dependently suppresses Gal-3 expression in MSCs and restores their immunoregulatory function.</p><p><strong>Conclusion: </strong>Gal-3 contributes to the decline in the immunomodulatory capabilities of MSCs. TD139, a Gal-3 inhibitor, has a potentially positive effect on rescuing the immunoregulation dysfunction of MSCs in late-passage and may represent a novel strategy to enhance the therapeutic potential of late-passage MSCs for GVHD treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"39918"},"PeriodicalIF":3.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Recruited Adipose Stromal Cells and Their Fibroblastic Differentiation in Cancer.","authors":"Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou","doi":"10.31083/FBL36559","DOIUrl":"https://doi.org/10.31083/FBL36559","url":null,"abstract":"<p><p>Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link between obesity and mortality observed in many cancer types that are surrounded by adipose tissue. In this review, we highlight recent findings on the characteristics and functions of ASCs in cancer and discuss their potential as therapeutic targets.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 8","pages":"36559"},"PeriodicalIF":3.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}