Biomedical Journal最新文献

{"title":"Impact of Genetic Variants in Cyclophosphamide-Metabolizing Enzymes on Clinical Outcomes After Haploidentical Hematopoietic Stem Cell Transplantation.","authors":"Ding-Ping Chen, Tung-Liang Lin, Gem Huai-Chueh Wu, Wei-Tzu Lin, Fang-Ping Hsu, Ching-Ping Tseng","doi":"10.1016/j.bj.2026.101010","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101010","url":null,"abstract":"<p><strong>Background: </strong>Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by post-transplant cyclophosphamide (CPA) treatment is an avenue to expand the pool of potential donors. This study aimed to investigate whether the gene polymorphisms related to CPA activation and metabolism are associated with the clinical outcomes of patients receiving haplo-HSCT.</p><p><strong>Methods: </strong>Genomic DNA from 35 haplo-HSCT patients were subject to analysis of 34 genetic polymorphisms located in CYP2B6, CYP2C19, ALDH1A1, ALDH3A1, GSTA1, GSTP1, GSTM1, and GSTT1 genes. The association of these gene polymorphisms with the occurrence of graft-versus-host disease (GVHD), relapse, and survival status of patients were analyzed by chi-square or Fisher's exact test under five genetic models, logistic regression analysis, and cumulative hazard curve analysis.</p><p><strong>Results: </strong>Age, gender, conditioning regimens, and the use of phenytoin were not associated with the clinical outcomes post-haplo-HSCT. Five SNPs in CYP2B6 (rs3745274 and rs8192719), CYP2C19 (rs 4244285 and rs3758580), and ALDH3A1 (rs2228100) genes were associated with chronic GVHD (cGVHD), acute GVHD (aGVHD) grade I-II, and GVHD, respectively. No SNPs were linked to survive or relapse. Logistic regression analysis adjusting for the use of phenytoin and conditional regimens and cumulative hazard curve analysis further demonstrated that rs375274 in the CYP2B6 gene was associated with the development of cGVHD, while rs222810 in the ALDH3A1 gene was associated with the development of aGVHD and aGVHD I-II for patients receiving haplo-HSCT.</p><p><strong>Conclusions: </strong>This study highlights the impacts of genetic polymorphisms related to CPA bioactivation and metabolism on the clinical outcomes of haplo-HSCT with post-transplant CPA. Despite the limited sample size and retrospective nature, identifying risk loci to enhance the transplant success rates for patients receiving haplo-HSCT is warranted.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101010"},"PeriodicalIF":4.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRMT5-mediated methylation of LKB1 controls PD-L1 expression in NSCLC.","authors":"Yi-Cheng Shen, Khuong T L Nguyen, Bo-Wei Wang, Fang-Ju Cheng, Bo-Rong Chen, Shu-Wei Hu, Po-Yu Chen, Jung-Mao Hsu, Ya-Ling Wei, Wei-Chien Huang, Chih-Yen Tu, Chia-Hung Chen","doi":"10.1016/j.bj.2026.101002","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101002","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis has significantly improved outcomes in non-small cell lung cancer (NSCLC), yet resistance remains a major clinical challenge. Protein arginine methyltransferase 5 (PRMT5) is an oncogenic regulator associated with poor prognosis, but its role in immune checkpoint modulation and underlying molecular mechanisms remain incompletely defined.</p><p><strong>Materials and methods: </strong>PRMT family expression and clinical correlations were analyzed using Oncomine, TCGA, and CPTAC databases. The effect of PRMT5 on PD-L1 was examined in LKB1-proficient and LKB1-deficient NSCLC cell lines using pharmacological inhibitors (GSK3326595, JNJ-64619178) and shRNA knockdown. Mechanistic analyses included co-immunoprecipitation (Co-IP), cycloheximide chase assays, and site-directed mutagenesis of LKB1 arginine residues. T-cell activation was evaluated using co-culture models.</p><p><strong>Results: </strong>Elevated PRMT5 expression in NSCLC was associated with poor survival, reduced CD4+/CD8+ T-cell infiltration, and higher PD-L1 expression in clinical datasets. Functional analyses revealed context-dependent regulation of PD-L1 by PRMT5. PRMT5 inhibition reduced or failed to induce PD-L1 in LKB1-deficient cells but upregulated PD-L1 in LKB1-proficient cells. Mechanistically, PRMT5 interacted with LKB1 and promoted its degradation through symmetric arginine dimethylation at R409. Conversely, PRMT5 inhibition stabilized LKB1, activated AMPK signaling, and induced PD-L1 expression in LKB1-proficient cells. Combination treatment with a PRMT5 inhibitor and anti-PD-L1 antibody further enhanced T-cell activation in co-culture models.</p><p><strong>Conclusion: </strong>These findings identify a PRMT5-LKB1-AMPK regulatory axis controlling PD-L1 expression in a cell-context-dependent manner and suggest that LKB1 status may serve as a predictive biomarker for combining PRMT5 inhibitors with ICB in NSCLC. This strategy offers a potential therapeutic avenue to overcome immunotherapy resistance in LKB1-proficient NSCLC.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101002"},"PeriodicalIF":4.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the 4-hydroxynonenal-regulated JNK/c-Jun pathway improves bleomycin-induced lung fibrosis","authors":"Chen-Chi Liu ,&nbsp;Jiun-Han Lin ,&nbsp;Tien-Wei Hsu ,&nbsp;Chien-Ying Wang ,&nbsp;Han-Shui Hsu","doi":"10.1016/j.bj.2025.100916","DOIUrl":"10.1016/j.bj.2025.100916","url":null,"abstract":"<div><h3>Background</h3><div>Lipid peroxidation and 4-hydroxynonenal (4-HNE) contribute to oxidative stress-related tissue damage, but their roles in pulmonary fibrosis remain unclear. We examined their involvement in bleomycin-induced pulmonary fibrosis.</div></div><div><h3>Materials and methods</h3><div>Lung fibrosis model mice were used to assess collagen deposition, lipid peroxidation markers, and oxidative stress. Ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO) were administered to the mice. <em>In vitro</em>, murine lung epithelial (MLE-12) cells were treated with bleomycin, with or without lipid peroxidation inhibitors, and analyzed for oxidative stress and apoptosis. 4-HNE expression in idiopathic pulmonary fibrosis lung tissues was assessed using immunohistochemistry.</div></div><div><h3>Results</h3><div>Bleomycin increased deposition of collagen and levels of 4-HNE and malondialdehyde levels while decreasing the glutathione/glutathione disulfide ratio. Fer-1 and DFO improved pulmonary function, reduced fibrosis, and restored the glutathione/glutathione disulfide ratio. <em>In vitro</em>, lipid peroxidation inhibition suppressed bleomycin-induced cell death and oxidative stress. Direct 4-HNE treatment induced apoptosis and lipid peroxidation, implicating 4-HNE in epithelial injury. 4-HNE upregulation was linked to increased transforming growth factor-β expression via c-Jun amino-terminal kinase/c-Jun signaling. Fer-1 and DFO mitigated these effects. Human idiopathic pulmonary fibrosis tissues exhibited elevated 4-HNE, correlating with fibrosis severity.</div></div><div><h3>Conclusions</h3><div>Lipid peroxidation and 4-HNE play key roles in pulmonary fibrosis progression. Their regulation of transforming growth factor-β expression suggests targeting lipid peroxidation as a potential therapeutic strategy.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100916"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphedema imaging and AI: A review of diagnostic modalities, biomarkers, and clinical integration","authors":"Bushra Urooj ,&nbsp;Sabir Ali ,&nbsp;Syed Kumail Hussain Naqvi ,&nbsp;Furen Xiao ,&nbsp;Po-Cheng Huang","doi":"10.1016/j.bj.2025.100932","DOIUrl":"10.1016/j.bj.2025.100932","url":null,"abstract":"<div><div>Lymphedema, a chronic lymphatic disorder characterized by swelling, fibrosis, and adipose tissue accumulation, requires precise, stage-specific imaging for effective diagnosis and management. This review evaluates conventional imaging modalities, including indocyanine green lymphography (ICG-L), lymphoscintigraphy, magnetic resonance imaging (MRI), and computed tomography (CT), alongside emerging artificial intelligence (AI) applications to enhance diagnostic accuracy and treatment planning. We analyze their capabilities in assessing lymphatic function and tissue changes through quantitative biomarkers, comparing their strengths across disease stages. ICG-L excels in detecting early lymphatic dysfunction, while MRI and CT provide detailed visualization of advanced fibrotic and adipose changes. AI-driven tools, such as automated segmentation and biomarker quantification, show promise in improving tissue characterization and supporting surgical planning. However, clinical integration of AI is hindered by data heterogeneity, lack of interpretability, and regulatory challenges. To address these, we propose a strategic framework incorporating federated learning for privacy-preserving model training, explainable AI for clinical transparency, and standardized imaging protocols. Future efforts should prioritize multicenter validation and harmonized guidelines to enhance reproducibility and ensure equitable, scalable adoption of advanced imaging technologies for lymphedema management worldwide.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100932"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence as a therapeutic target for aging intervention","authors":"Youkun Bi ,&nbsp;Guangju Ji","doi":"10.1016/j.bj.2026.100948","DOIUrl":"10.1016/j.bj.2026.100948","url":null,"abstract":"<div><div>Cellular senescence is a stress-induced cellular state that contributes to tissue dysfunction, chronic inflammation, and a broad range of aging-associated pathologies. The accumulation of senescent cells (SnCs) disrupt normal tissue function, positioning them as drivers of pathological decline and therapeutic targets for aging intervention. Accordingly, multiple senescence-targeted strategies have been developed, including senolytics, senomorphics, senescence immunotherapy, and restoration-oriented interventions. These approaches aim to mitigate senescence-driven pathology by eliminating senescent cells, modulating their secretory activity, or restoring cellular function. Ongoing advancements will require precise stratification of senescent states, careful assessment of long-term safety, and the integration of optimized delivery systems for targeted therapeutic outcomes.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100948"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro axotomy models regulated by ROCK inhibitor for studying neuroregeneration and growth cone morphology","authors":"Fang Fang ,&nbsp;Dan Xu ,&nbsp;Shuang Dou ,&nbsp;Shaoqin Zhan ,&nbsp;Yingjuan Fan ,&nbsp;Yuehong Zhuang ,&nbsp;Weihong Xu ,&nbsp;Zixing Xu","doi":"10.1016/j.bj.2025.100908","DOIUrl":"10.1016/j.bj.2025.100908","url":null,"abstract":"<div><div>Current complex models of human nerve injury hinder the identification of cellular responses and the screening of therapies. As a solution, simpler in vitro axotomy models utilizing embryonic rat dorsal root ganglion (DRG) and spinal motor neuron aggregates (SMNAs) have been introduced. To ensure model consistency, DRG or SMNA was placed in a cross-shaped channel for axotomy, performed microscopically with a razor. Afterward, the expression of four regeneration-associated genes (RAGs) and regulatory genes was assessed, along with quantifying axon outgrowth and growth cone changes in response to ROCK inhibitor Y27632. Additionally, a mouse perforator flap model was created to evaluate Y27632's effect on DRG axon reinnervation. It turned out that complete and consistent severance of the axons from the DRGs and SMNAs could be easily achieved, with significantly increased expressions of the four RAGs, Rho A and ROCK2. Y27632 could significantly augment axon regeneration in DRGs with axotomy in vitro and in the flap model but showed no impact on DRG axon outgrowth without axotomy. In comparison, Y27632 could slightly increase axon outgrowth from SMNAs without axotomy but drastically boost the axon regeneration from SMNAs with axotomy. The growth cones of DRGs and SMNAs drastically shrunk after axotomy, which could be significantly expanded by Y27632. In contrast, no impact on the growth cones of DRG and SMNAs without axotomy by Y27632 could be observed. The novel in vitro axotomy models regulated by ROCK inhibitors can be used to optimize studies on peripheral nerve injury-related drug screening by observing neuroregeneration and growth cone changes.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100908"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GR/HDAC2/synaptic complexes in hippocampal CA1 mediate the antidepressant effects of magnolol","authors":"Yu-Qian Jiang ,&nbsp;Qing-Yu Kuang ,&nbsp;Yuan Xu ,&nbsp;Yi-Xiang Xu ,&nbsp;Jie Cheng ,&nbsp;Li-Tao Yi","doi":"10.1016/j.bj.2026.100961","DOIUrl":"10.1016/j.bj.2026.100961","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a multifactorial neuropsychiatric disorder linked to neuroinflammation and epigenetic dysregulation, particularly in histone acetylation. Although magnolol has demonstrated antidepressant-like properties, its precise molecular mechanisms remain unclear. This study aimed to evaluate the antidepressant effects of magnolol and its influence on epigenetic regulation of synaptic plasticity in a chronic unpredictable mild stress (CUMS) mouse model.</div></div><div><h3>Material and methods</h3><div>C57BL/6 mice subjected to CUMS were treated orally with magnolol. Depressive-like behaviors were assessed using standard behavioral tests. Expression levels of histone deacetylase 2 (HDAC2), synaptic proteins such as neuroligin-1 (NLGN1) and neurexin-1β (NRXN1β), and their associated co-localized puncta were examined. Golgi staining and immunofluorescence were performed to assess dendritic spine density and DCX-positive cell population in the hippocampus.</div></div><div><h3>Results</h3><div>Magnolol treatment alleviated depressive-like behaviors, evidenced by increased sucrose preference and reduced immobility in behavioral assays. It also attenuated hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as shown by normalization of serum corticosterone levels and restoration of glucocorticoid receptor (GR) expression in the hippocampal CA1 region. At the molecular level, magnolol reduces HDAC2 expression, which may be associated with altered histone acetylation, thus upregulation of NLGN1 and NRXN1β, enhancing the formation of pre- and postsynaptic co-localized puncta. Additionally, magnolol promoted hippocampal DCX-positive cell population and synaptogenesis, supporting improvements in structural and functional neuroplasticity.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate the ability of magnolol to modulate histone acetylation and synaptic architecture involved in its antidepressant-like action. These results provide a foundation for further exploration of magnolol-based interventions targeting epigenetic and synaptic mechanisms in depression.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100961"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Displaced minds: ecologies of depression","authors":"Aila Akosua Kattner","doi":"10.1016/j.bj.2026.101000","DOIUrl":"10.1016/j.bj.2026.101000","url":null,"abstract":"<div><div>This issue of the <em>Biomedical Journal</em> explores emerging perspectives across neuropsychiatry, metabolism, aging, regenerative medicine, artificial intelligence, and chronic inflammatory disease. Featured contributions examine epigenetic and neuroendocrine mechanisms in depression, including the antidepressant-like effects of magnolol in chronic stress-induced models and the potential relevance of short-chain fatty acids as biomarkers and therapeutic targets in major depressive disorder. Additional reviews address evolutionary and metabolic dimensions of liver disease, artificial intelligence-assisted imaging approaches in lymphedema, immunological senotherapeutic strategies, developmental origins of cardiovascular-kidney-metabolic syndrome, and the risks associated with short-term corticosteroid exposure. Original investigations further examine dopaminergic signaling during acute deprivation, molecular mechanisms of axonal regeneration, lipid peroxidation in pulmonary fibrosis, hypothalamic NPFFR2 signaling in metabolic dysfunction, neurobehavioral consequences of occlusal disharmony, and fall risk following cataract surgery with blue-light-filtering intraocular lenses. A correspondence exchange additionally discusses the diagnostic scope and limitations of elastase pretreatment in ALK fluorescence in situ hybridization analysis for non-small cell lung cancer.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 101000"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the safety of short-term systemic corticosteroids","authors":"Hui-Ju Tsai ,&nbsp;Tsung-Chieh Yao","doi":"10.1016/j.bj.2026.100962","DOIUrl":"10.1016/j.bj.2026.100962","url":null,"abstract":"<div><div>Short-term systemic corticosteroids are widely prescribed to treat acute flare-ups of chronic immunologic diseases or to manage acute inflammatory conditions such as allergic reactions, skin disorders, and respiratory infections. This review revisits the safety of short-term systemic corticosteroids, focusing on emerging evidence of their potential unexpected risks. Epidemiological studies reveal an increasing trend in prescribing of short-term systemic corticosteroids in the general population. However, concerns have been raised regarding the safety of short-term oral corticosteroids, with recent evidence suggesting that even corticosteroid bursts are associated with rare but serious adverse events, including sepsis, pneumonia, gastrointestinal bleeding, acute pancreatitis, heart failure, venous thromboembolism, and fracture. Recent studies also highlight long-term risks of antenatal corticosteroids. While crucial for reducing neonatal respiratory distress syndrome in pregnancies at risk of preterm delivery, antenatal corticosteroids are linked to long-term risks of neuropsychiatric disorders, serious infections, and even mortality in children, along with heightened risks of infections, heart failure, and gastrointestinal bleeding among mothers. These findings suggest the potential harms of short-term systemic corticosteroids may have been previously underrecognized. Raising awareness of these risks can help clinicians balance therapeutic benefits against potential harms and promote safer clinical practice. Cautious and evidence-based approaches to prescribing short-term systemic corticosteroids are necessary, particularly in vulnerable populations. Further research is needed to develop a “corticosteroid stewardship” approach that promotes appropriate prescribing of systemic corticosteroids, minimizes unnecessary use, and ensures careful monitoring of adverse effects to optimize patient outcomes.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100962"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental origins and environmental determinants of cardiovascular–kidney–metabolic syndrome: A pediatric precision prevention perspective","authors":"You-Lin Tain ,&nbsp;Chien-Ning Hsu","doi":"10.1016/j.bj.2026.100970","DOIUrl":"10.1016/j.bj.2026.100970","url":null,"abstract":"<div><div>Cardiovascular–Kidney–Metabolic Syndrome (CKMS), formally defined by the American Heart Association in 2023, emphasizes the interconnections among chronic kidney disease, cardiovascular disease, obesity, and diabetes. Although CKMS typically manifests in adulthood, accumulating evidence indicates that vulnerability is established early in life through developmental programming shaped by maternal, perinatal, and early-childhood exposures. This review summarizes the developmental origins, environmental determinants, and mechanistic pathways of CKMS, with a particular emphasis on kidney programming and pediatric precision prevention. Recent nationally representative data indicate that CKMS risk-stage (stage ≥1) affects approximately 90% of U.S. adults and 40% of adolescents, highlighting the extensive population burden long before overt clinical disease develops, yet kidney health remains underrecognized within cardiometabolic risk assessment. In children, early metabolic disruption, excess adiposity, and subclinical cardiovascular dysfunction interact with structural or developmental renal vulnerability to accelerate CKD progression and amplify lifelong risk. Evidence from the Developmental Origins of Health and Disease framework demonstrates that maternal malnutrition, metabolic disease, toxicant exposures, preterm birth, and perinatal complications permanently alter nephron endowment, vascular function, and metabolic regulation. Animal studies reveal convergent mechanisms—including oxidative stress, aberrant renin–angiotensin activity, epigenetic modifications, gut microbiota dysbiosis, and sex-specific responses—that predispose offspring to CKMS and highlight targets for early-life reprogramming. Prevention should begin with maternal health and the first 1000 days, incorporating nutritional and lifestyle interventions, early screening for obesity, hypertension, and dyslipidemia, and emerging microbiome- or antioxidant-targeted therapies. Advances in multi-omics, digital health, and AI-enabled monitoring facilitate early risk stratification and precision prevention, although pediatric-specific guidelines remain limited. Viewed through a life-course lens, CKMS represents a gradual, self-reinforcing process rooted in developmental programming and environmental exposures. Integrating maternal and pediatric interventions within a life-course precision prevention framework provides a roadmap to disrupt disease trajectories, reduce intergenerational risk, and promote lifelong cardiovascular, kidney, and metabolic health.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 3","pages":"Article 100970"},"PeriodicalIF":4.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}