Frontiers in bioscience (Landmark edition)最新文献

{"title":"Novel Insight into the Multiple Biological Characteristics of Polyamines in the Gut: From Structure to Function.","authors":"Xinyi Yu, Shuzi Xin, Xiaohui Liu, Luming Pan, Weikai Shi, Yize Li, Hongli Wang, Xin Lu, Han Gao, Jingdong Xu","doi":"10.31083/FBL27929","DOIUrl":"https://doi.org/10.31083/FBL27929","url":null,"abstract":"<p><p>This review explores the structure of polyamines, including putrescine, spermidine, and spermine, and their crucial roles in immune cell functions. Polyamines are active compounds derived from ornithine that regulate signaling pathways by interacting with nucleic acids and proteins. Polyamines are essential for normal growth and development in immune cells, participating in cell signaling and neurotransmitter regulation and playing a critical role in immune responses. Notably, high concentrations of polyamines play a significant role in tumor cells and autoreactive B and T cells in autoimmune diseases. This impact should not be overlooked. Elevated levels of polyamines are associated with enhanced immune cell activity in tumor cells and autoimmune diseases. Furthermore, the connection between polyamines and normal immune cell functions, as well as their roles in autoimmune and antitumor immune cell functions, is significant. The role of polyamines in the normal function of activated T cells is well-established, and they are particularly important in antitumor immunity by modulating immune cell functions in the tumor microenvironment (TME). By synthesizing the latest research advancements, this review provides valuable insights into the roles of polyamines in immune regulation and outlines directions for future research.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 7","pages":"27929"},"PeriodicalIF":3.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790929","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":"Interleukin-31: A Pro-inflammatory Oriented Cytokine.","authors":"Giuseppe Murdaca, Francesca Paladin, Andrea Orsi, Sebastiano Gangemi","doi":"10.31083/FBL37462","DOIUrl":"https://doi.org/10.31083/FBL37462","url":null,"abstract":"<p><p>Type 2 immunity is represented by T helper 2 (Th2) lymphocytes and the cytokines produced downstream (Interleukin (IL)-4, IL-13, IL-31). They are increasingly recognized as pivotal mediators in the pathogenesis of immune-mediated dermatological conditions such as atopic dermatitis (AD) and psoriasis (Pso). In these disorders, they initiate and amplify immunological signaling cascades, promote cutaneous inflammation, and contribute to the induction of pruritus. In this context, IL-33 and IL-31 would be believed to be intrinsically linked and related to the acuity of the disease. The presence of an interleukin could in fact trigger the other, amplifying the inflammatory process of itchy skin disorders and therefore the extent of the symptoms. High levels of IL-31 may support the maintenance of a microenvironment that promotes both the growth and spread of solid tumors, as well as the development of cancer-associated pruritus. Given these premises, non-histaminergic mediators such as IL-31 and IL-33 could be explored as novel therapeutic targets for the treatment of pruritus in immune-mediated skin diseases and cancer, improving the QoL of patients. Finally, we briefly discussed the recent innovations in the field of monoclonal anti-IL-31 therapies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"37462"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562211","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":"Aldo-keto Reductase 1B10 (AKR1B10) Suppresses Sensitivity of Ferroptosis in TNBC by Activating the AKT/GSK3β/Nrf2/GPX4 Axis.","authors":"Shanli Wu, Gun Yang, Xiaosha Wen, Yi Lin, Shenglong Wang, Jing Wang, Quan Liu, Dixian Luo","doi":"10.31083/FBL36615","DOIUrl":"https://doi.org/10.31083/FBL36615","url":null,"abstract":"<p><strong>Background: </strong>Aldo-keto reductase 1B10 (AKR1B10) is expressed in various malignant tissues. Several studies have highlighted the essential function of AKR1B10 in lipid metabolism and in the detoxification of lipid peroxides. The aim of this research was to explore the role of AKR1B10 in the susceptibility of MDA-MB-231 cells to ferroptosis. These cells serve as a model for triple-negative breast cancer (TNBC).</p><p><strong>Methods: </strong>Lentiviral transfection was used to establish stable cell lines with high or low expression of AKR1B10. Our model of ferroptosis used the ferroptosis activator RSL3, and the specific ferroptosis inhibitor ferrostatin-1 (Fer-1) to rescue cell death. Stable cell lines were treated with the specific inhibitor OSU-T315 directed against phosphorylation of Ser473 in protein kinase B (AKT) and Ser9 in glycogen synthase kinase 3 beta (GSK3β), either alone or in combination with RSL3. A fatty acid stress model was established using palmitic acid (PA) or arachidonic acid (AA), either in the presence or absence of serum starvation and with or without co-treatment with RSL3. Cell viability was evaluated with the cell counting kit-8 (CCK8) assay and lipid peroxidation levels by flow cytometry after staining with C11 BODIPY 581/591. Exploration of the underlying mechanisms was conducted through RNA sequencing and bioinformatics analysis. Western blotting was performed to evaluate protein levels, and quantitative real-time polymerase chain reaction (qPCR) was used to evaluate transcript levels.</p><p><strong>Results: </strong>Western blot and qPCR analyses validated the successful establishment of stable MDA-MB-231 cell lines with and without AKR1B10 overexpression. Cell viability and lipid reactive oxygen species (ROS) assays showed that AKR1B10 suppressed ferroptosis in the RSL3-induced cell death model. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses indicated the phosphatidylinositol 3-kinase (PI3K)-AKT pathway was likely to play a role in the underlying mechanisms. AKR1B10 increased the expression of glutathione peroxidase 4 (GPX4), thus potentially implicating the AKT/GSK3β/nuclear factor erythroid 2-related factor 2 (NRF2)/GPX4 pathway in the mechanism. These changes in protein levels were also observed by Western blot analysis after 6 h of RSL3 treatment. Under the influence of RSL3, the transcript levels of NRF2-related genes including <i>GPX4</i>, ferritin heavy chain 1 (<i>FTH1</i>), heme oxygenase 1 (<i>HO-1</i>), and NAD(P)H quinone dehydrogenase 1 (<i>NQO-1</i>) were significantly elevated in the AKR1B10 overexpression cell line, whereas that of prostaglandin-endoperoxide synthase 2 (<i>PTGS2</i>) was significantly reduced. Similar changes were observed after treatment with OSU-T315. AKR1B10 was found to suppress the sensitivity to ferroptosis induced by treatment with OSU-T315, PA, or AA. These phenomena were rescued by the ferroptosis inhibito","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"36615"},"PeriodicalIF":3.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562188","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":"Functional Verification and Prognostic Value of Neutrophil Extracellular Trap-Related Genes in Pancreatic Cancer Progression.","authors":"Jiaxin Xu, Liying Tu, Lijing Ma, Qisheng Tang, Yu Cao, Lihong Jiang","doi":"10.31083/FBL38830","DOIUrl":"https://doi.org/10.31083/FBL38830","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic carcinoma (PC), a severely malignant neoplasm of the digestive system, is characterized by an unfavorable prognosis. Neutrophil extracellular trap (NETosis) is a neutrophilic inflammatory form of cell death. However, it is still unknown how they relate to one another. This study aims to explore the part NETosis plays in the onset and progression of pancreatic cancer.</p><p><strong>Methods: </strong>Expression and clinical data for patients with pancreatic carcinoma were obtained from publicly accessible databases. Multigene features were constructed using the least absolute shrinkage and selection operator (LASSO). Bioinformatics analysis was combined with <i>in vitro</i> experiments to determine the relevant mechanism.</p><p><strong>Results: </strong>Seventeen NETosis-related genes were identified. LASSO analysis finally led to the generation of six gene characteristics, which were divided into two clusters according to the expression level. The survival outcomes of the high- and low-risk groups differ significantly, and their predictive performance is good (<i>p</i> < 0.05). Drug sensitivity analysis confirmed that the high-risk cohort could benefit more from 5-fluorouracil, gemcitabine, and epirubicin (<i>p</i> < 0.01). Using survival analysis and single-cell binding quantitative real-time polymerase chain reaction (RT-qPCR), the crucial gene <i>LGALS3</i> was identified (<i>p</i> < 0.0001). <i>In vitro</i> experiments demonstrated that inhibiting <i>LGALS3</i> expression may significantly decrease the proliferation and movement of PANC-1 and SW1990 cells (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>We established a 6-gene risk scoring model and confirmed the effect of <i>LGALS3</i> on the development of PC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"38830"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562209","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":"<i>Lactobacillus reuteri</i> E9 Regulates Sleep Disorders Through Its Metabolite GABA.","authors":"Yongcheng Jiang, Lina Guo, Houde He, Haonan Chen, Tao Chen, Yan Liu, Wang Zhao","doi":"10.31083/FBL39587","DOIUrl":"https://doi.org/10.31083/FBL39587","url":null,"abstract":"<p><strong>Background: </strong>Insomnia, the most prevalent sleep disorder, is clinically defined as difficulty initiating or maintaining sleep. Although many medications are effective for insomnia treatment, they carry risks of drug dependence and abuse. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signaling between the gastrointestinal tract and the central nervous system via gut microbes. Probiotics that provide mental and behavioral benefits through MGBA (psychobiotics) offer broad therapeutic potential.</p><p><strong>Methods: </strong>A non-toxic, drug-resistant strain of <i>Lactobacillus reuteri</i> E9 was isolated and characterized. Its effects were evaluated in a pentylenetetrazol (PTZ)-induced zebrafish model of sleep disorder. Neurotransmitter levels (glycine, serine, taurine, γ-aminobutyric acid (GABA)) and gene expression of GABA/melatonin receptors were analyzed.</p><p><strong>Results: </strong>E9 significantly upregulated inhibitory neurotransmitters, including GABA, taurine, glycine, and serine (<i>p</i> < 0.05). In PTZ-induced zebrafish, E9 exerted sedative effects by reducing seizures and hyperactivity. Concurrently, E9 upregulated the expression of GABA receptor genes and melatonin receptor (Mtnr1aa) genes in zebrafish neural tissue.</p><p><strong>Conclusions: </strong><i>Lactobacillus reuteri</i> E9 demonstrates potential as a psychobiotic for sleep disorder management by modulating key inhibitory neurotransmitters and sleep-related receptor expression via the MGBA pathway, offering a non-pharmacological alternative to conventional treatments.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"39587"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562184","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":"Study of the Function and Expression of the <i>AhRUVBL2</i> Promoter in <i>Arabidopsis</i>.","authors":"Penghui Miao, Xuanlin Li, Yongshan Wan, Kun Zhang, Haiyang Yu, Yuying Li, Huadong Li, Hui Yang, Lu Luo, Fengzhen Liu","doi":"10.31083/FBL38940","DOIUrl":"https://doi.org/10.31083/FBL38940","url":null,"abstract":"<p><strong>Background: </strong>Cultivated peanut (<i>Arachis hypogaea</i> L.) is a major oil and economic crop. Pod size is one of the important agronomic traits of peanut variety, with a direct impact on peanut yield.</p><p><strong>Methods: </strong>In a previous study, <i>AhRUVBL2</i> was identified by map-based cloning technology as a candidate gene that regulates peanut pod size.</p><p><strong>Results: </strong>Overexpression of <i>AhRUVBL2</i> in transgenic <i>Arabidopsis</i> significantly increased plant height, branch number, leaf size, silique size, seed size, and thousand-seed weight. Further examination revealed an increase in the area of silique exocarp cells, and the number and area of endocarp lignified cells. A total of 337 differentially expressed genes, including <i>PRX</i> (<i>Periaxin</i>) , <i>SAUR</i> (<i>Small Auxin-up RNA</i>), and <i>PYL</i> (<i>Pyrabactin Resistance 1-like</i>), were identified by transcriptome analysis of transgenic <i>Arabidopsis</i> silique. <i>proAhRUVBL2-GUS</i> was found to be expressed explicitly in seeds, and the expression activity of <i>proAhRUVBL2-D893</i> was significantly greater than that of <i>proAhRUVBL2-79266</i>. Exogenous ABA (abscisic acid) and IAA (indole acetic acid) treatment of <i>proAhRUVBL2-GUS</i>-transformed tobacco leaves revealed that the <i>AhRUVBL2</i> promoter was hormone-responsive.</p><p><strong>Conclusions: </strong>This study sheds light on the function of <i>AhRUVBL2</i> in regulating plant growth and development. Moreover, characterization of the <i>AhRUVBL2</i> promoter provides a valuable genetic resource for enhancing peanut yield.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"38940"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562153","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":"Changes in Corneal Keratocytes and Collagen Fibrils as an Indicator of Keratoconus Onset: A Preliminary Study Based on OCT Subchannel Images.","authors":"Frederick H Silver, Dominick Benedetto, Tanmay Deshmukh","doi":"10.31083/FBL38750","DOIUrl":"https://doi.org/10.31083/FBL38750","url":null,"abstract":"<p><strong>Background: </strong>Keratoconus (KC) is a corneal disease that causes changes in corneal topography, leading to central/paracentral cone formation, which affects visual acuity.</p><p><strong>Methods: </strong>We studied <i>in vivo</i> optical coherence tomography (OCT) images of normal and KC corneas images. The relative cellular and collagen content in the control and KC human corneas was measured by collecting OCT images and then dividing the images into low (green), medium (blue), and high pixel intensity (red) subchannel images. The green image was used to evaluate the cellular content in the cornea, the blue image presented information on the collagen content, and the red image provided information on both the cellular and collagen contents.</p><p><strong>Results: </strong>These results suggest that the cellular and collagen contents decrease with increased corneal depth in KC, while the collagen content appears to reduce as changes in the keratocyte content occur.</p><p><strong>Conclusion: </strong>This study proposes that using the green, blue, and red subchannel OCT images may be an effective method for detecting KC and other corneal diseases earlier, before observing changes in corneal topography, and that these images can be collected remotely using telemedicine.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"38750"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562205","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":"Atorvastatin Calcium Enhances Ferroptosis in Breast Cancer Cells Through Mechanisms Involving DECR1.","authors":"Yao Li, Hongdan Chen, Zeyu Yang, Yinde Huang, Fan Zhang, Huaizhi Wang","doi":"10.31083/FBL38924","DOIUrl":"https://doi.org/10.31083/FBL38924","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is currently the most prevalent malignancy among females, representing a substantial threat to both physical and psychological health. Moreover, its incidence rate continues to rise annually. Therefore, screening potential therapeutic targets and developing candidate drugs for breast cancer treatment holds significant clinical implications.</p><p><strong>Methods: </strong>In this study, <i>in silico</i> methods were used to identify potential therapeutic targets of fatty acid metabolism-related genes in breast cancer and to screen potential drugs using molecular docking. In addition, Cell Counting Kit-8 (CCK-8) and Transwell assays were utilized to analyze the effect of atorvastatin calcium (AC) on the malignant phenotype of breast cancer cells. Furthermore, the effects of AC-induced ferroptosis in tumor cells were evaluated using transmission electron microscopy, ROS, Fe²⁺, and Liperfluo probes, and the potential molecular mechanisms were explored through real-time qPCRand western blotting.</p><p><strong>Results: </strong>2,4-Dienoyl-CoA Reductase 1 (DECR1) overexpression was related to a dismal prognostic outcome in breast cancer patients. AC interfered with breast cancer cell proliferation and invasion, potentially through its effects in DECR1 expression, while suppressing tumor growth <i>in vivo</i>. In addition, AC demonstrated antitumor effects, possibly through the downregulation of DECR1 and the upregulation of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), which may contribute to the induction of ferroptosis in tumor cells.</p><p><strong>Conclusions: </strong>DECR1 is associated with breast cancer progression and may serve as a potential therapeutic indicator, and AC plays an antitumor role by modulating DECR1 expression and promoting ACSL4-mediated ferroptosis. Therefore, AC may be considered a potential candidate drug for treating breast cancer.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"38924"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562204","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 Lysine Tyrosylquinone Containing Oxidases in Progression of Solid Tumors.","authors":"Tatyana V Korneenko, Nikolay B Pestov, Nickolai A Barlev","doi":"10.31083/FBL36248","DOIUrl":"https://doi.org/10.31083/FBL36248","url":null,"abstract":"<p><p>Lysine tyrosylquinone (LTQ), the cofactor formed through copper-assisted tyrosine oxidation and subsequent intramolecular cross-linking, is inherent in all members of the lysyl oxidase family. Lysyl oxidases are unique among amine oxidases in that they maintain the LTQ coenzyme in a relatively surface-exposed position, making it accessible for the oxidative deamination of lysine side chains in various proteins, especially in the extracellular matrix. This process facilitates the formation of intramolecular cross-links, which are vital for the normal development of skin, bones, aorta, and other tissues. Unfortunately, in accordance with the antagonistic pleiotropy theory of aging, the enzyme activity that is essential in youth may become non-optimal throughout the lifespan. One consequence of excessive lysyl oxidase and its ectopic activity in the nucleus is the promotion of stiffness in solid tumors and increased survival of metastasizing cells. Therefore, LTQ-dependent oxidative deamination, especially at the stage of LTQ formation, is a promising druggable target for future combination therapies aimed at treating the most lethal cancers.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"36248"},"PeriodicalIF":3.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562157","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 Exosome-Loaded Hydrogels in Improving Intervertebral Disc Degeneration: A Systematic Review and Meta-Analysis of Preclinical Animal Studies.","authors":"Bowen Wang, Desheng Xie, Jianming Huang, Zheyuan Huang, Weizong Weng, Danlei Huang, Ying Zhang, Xiaolin Chen","doi":"10.31083/FBL38302","DOIUrl":"10.31083/FBL38302","url":null,"abstract":"<p><strong>Objective: </strong>Intervertebral disc degeneration (IDD) is a major cause of chronic lower back pain, with current treatment options offering limited efficacy. Exosome-loaded hydrogels have emerged as a promising therapeutic approach due to their biocompatibility and regenerative potential, making them a focus of research for IDD treatment. This study systematically evaluates and performs a meta-analysis of the effectiveness of exosome-loaded hydrogels in preclinical models of IDD.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across four major databases (PubMed, Embase, Cochrane, Web of Science), including animal studies that met predefined criteria. Data extraction and quality assessment were independently performed by two authors. Treatment effects were quantified using standardized mean differences (SMD) with 95% confidence intervals (CI). Outcome measures included disc height index (DHI), magnetic resonance imaging (MRI) grade, histological grade, IDD-related immunohistochemical (IHC) markers (e.g., collagen type II (COL2), matrix metalloproteinase 13 (MMP13)), and aging-related markers (e.g., p16Ink4a-positive cells, p21CIP1A-positive cells).</p><p><strong>Results: </strong>Treatment with exosome-loaded hydrogels significantly enhanced DHI scores at 4 (<i>p</i> = 0.002) and 8 weeks (<i>p</i> < 0.0001), and decreased MRI scores at 8 (<i>p</i> < 0.00001) and 12 weeks (<i>p</i> < 0.0001), and histological assessments. Furthermore, the treatment group exhibited increased COL2 expression at 8 (<i>p</i> = 0.0002) and 12 weeks (<i>p</i> = 0.002), decreased MMP13 levels at 8 (<i>p</i> = 0.0001) and 12 weeks (<i>p</i> = 0.0009), and a reduction in aging markers (p16Ink4a, p21CIP1A, all <i>p</i> < 0.05), suggesting that exosome-loaded hydrogels facilitate intervertebral disc repair through the modulation of molecular pathways. Sensitivity analysis confirmed the robustness of the findings.</p><p><strong>Conclusions: </strong>Exosome-loaded hydrogels show potential for improving the structure and function of intervertebral discs in IDD treatment, potentially slowing degeneration by inhibiting matrix degradation and cellular aging. Further investigation is required to elucidate the underlying mechanisms and to assess the safety and efficacy of these hydrogels for clinical application. The PROSPERO Registration: CRD420250649970 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420250649970).</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 6","pages":"38302"},"PeriodicalIF":3.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562155","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}