Haixia Huang, Yahong Zhou, Jing Hu, Fan Jia, Yong Tan
{"title":"The mechanism of polycystic ovarian syndrome induced by circadian rhythm disturbance and the therapeutic effect of melatonin.","authors":"Haixia Huang, Yahong Zhou, Jing Hu, Fan Jia, Yong Tan","doi":"10.3164/jcbn.25-255","DOIUrl":"10.3164/jcbn.25-255","url":null,"abstract":"<p><p>Environmental factors are crucial causes of polycystic ovary syndrome (PCOS). There is growing evidence of an association between circadian rhythm disturbance and PCOS, but the underlying molecular mechanisms This study aimed to explore the molecular mechanism of PCOS induced by circadian rhythm disturbance and evaluate the therapeutic potential of melatonin. A rat model of circadian rhythm disturbance was established via 24-h continuous light exposure. Rats were randomly divided into the Control group (normal circadian rhythm), Model group (continuous light exposure), and Model + Melatonin treatment group (continuous light exposure + melatonin). Reproductive endocrine indicators, ovarian histomorphology, and ovarian granulosa cell (GC) function were assessed. Additionally, circadian rhythms of serum hormones, autophagy-related markers (LC3), and hypothalamic clock genes were detected at six zeitgeber time (ZT) points. Autophagy and apoptosis levels in GCs, as well as the activation of MAPK and PI3K/Akt/mTOR pathways, were also detected. Continuous light exposure induced PCOS-like phenotypes in rats, characterized by disrupted estrous cycles, cystic ovarian changes, and loss of circadian rhythms in serum hormones, autophagy marker LC3, and hypothalamic clock genes. Moreover, continuous light exposure reduced GC viability, increased GC autophagy and apoptosis, activated the MAPK pathway, and inhibited the PI3K/Akt/mTOR pathway in GCs. Melatonin treatment significantly ameliorated these PCOS-like phenotypes. Our study showed circadian rhythm disturbance induced PCOS via MAPKs and PI3K/Akt/mTOR signaling pathways and increased autophagy level in rat ovarian GCs. Melatonin had a therapeutic effect on PCOS by reversing these signaling pathway abnormalities and reducing autophagy and apoptosis levels in GCs.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"76-85"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-aging effects of glycyrrhizin via maintaining Klotho levels.","authors":"Shiho Ohnishi, Keiichi Hiramoto, Nobuji Yoshikawa, Shosuke Kawanishi","doi":"10.3164/jcbn.25-263","DOIUrl":"10.3164/jcbn.25-263","url":null,"abstract":"<p><p>Klotho, an anti-aging protein, controls the insulin-like growth factor-1 (IGF-1) and suppresses inflammation implicated in senescence. We previously reported that glycyrrhizin (GL), a medicinal ingredient of licorice root, significantly attenuates inflammatory responses by inhibiting high-mobility group box 1 (HMGB1). In this study, we investigated whether GL is effective in suppressing the decline in Klotho levels and aging-induced frailty. After oral administration of GL three times a week for 12 months, the following effects were observed: reductions in the increases in blood fats, steatoses, obesity, and kidney aging; maintenance of activity level and rotarod test performance. Furthermore, we found beneficial effects of GL on the blood levels of functional proteins; upregulation of anti-aging factors, IGF-1 and Klotho; decrease in cystatin-C, an indicator of declining kidney function; and decreases in IL-6 and TNF-α, inflammatory cytokines. GL also seemed to increase superoxide dismutase 2, an antioxidant enzyme, in the liver and kidneys. As GL can inhibit HMGB1, it may attenuate this inflammatory amplification loop, reducing the systemic senescence-associated secretory phenotype and thus mitigating multiple aging phenotypes by maintaining Klotho levels.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"104-110"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic potential of hydrogen-rich water (HRW) in oxidative stress-related diseases.","authors":"Wafaa H Mohamed, Idris Long","doi":"10.3164/jcbn.26-5","DOIUrl":"10.3164/jcbn.26-5","url":null,"abstract":"<p><p>Oxidative stress is a central mechanism in metabolic, cardiovascular, and neurodegenerative diseases, contributing to inflammation, mitochondrial dysfunction, and apoptosis. Consequently, redox-modulating therapies are increasingly explored as potential therapeutic strategies. This review evaluates the mechanistic basis, experimental evidence, and clinical applicability of hydrogen-rich water (HRW) in oxidative stress-related diseases. A structured literature search identified mechanistic, preclinical, and clinical studies investigating HRW or molecular hydrogen (H<sub>2</sub>) on oxidative stress, inflammation, mitochondrial regulation, and disease-related outcomes. Due to substantial methodological heterogeneity, findings were synthesized qualitatively. HRW has been proposed to selectively neutralize highly reactive species such as hydroxyl radicals (<sup>•</sup>OH) and peroxynitrite (ONOO<sup>-</sup>) while preserving physiological reactive oxygen species signalling. Mechanistic studies demonstrate activation of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathways, suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory cascades, modulation of JAK/STAT signalling, preservation of mitochondrial bioenergetics, and enhancement of autophagic regulation. Preclinical and clinical studies report improvements in glycaemic control, endothelial function, cardiometabolic health, neuroprotection, exercise performance, and treatment-related fatigue. Despite an excellent safety profile, standardization of HRW preparation and large multicentre randomized controlled trials (RCTs) remain necessary to establish clinical efficacy and translational potential.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"15-27"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of nine dietary minerals on the risk of chronic kidney disease: a multi-model analysis in US adults using NHANES data.","authors":"Zhuoga Cairen, Xinyun Chen, Shenju Gou, Ping Fu","doi":"10.3164/jcbn.25-251","DOIUrl":"10.3164/jcbn.25-251","url":null,"abstract":"<p><p>Chronic kidney disease (CKD), affecting 8-16% of the global population, presents substantial public health burdens. While constituting only 5% of daily dietary intake, minerals critically influence physiological processes. This study investigates associations between dietary mineral intake and CKD risk; utilizing publicly available data from the National Health and Nutrition Examination Survey (NHANES), we employed multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS), quantile-based g-computation (QGcomp), and Bayesian kernel machine regression (BKMR) models to assess CKD-mineral relationships; multivariate logistic regression revealed significant inverse associations between CKD risk and calcium (OR = 0.72), phosphorus (OR = 0.69), magnesium (OR = 0.65), copper (OR = 0.81), potassium (OR = 0.85), and zinc (OR = 0.88). RCS analysis demonstrated linear protective trends for calcium, phosphorus, zinc, potassium, and selenium, while magnesium, iron, and copper exhibited U-shaped dose-response patterns. WQS regression identified a protective mineral mixture (weighted index OR = 0.83), with magnesium (35.2%) and calcium (28.1%) as primary contributors. QGcomp analysis highlighted magnesium's protective effect (-0.21 risk score) contrasting with iron's adverse association (+0.18). BKMR modeling confirmed magnesium's significant protection (PIP = 0.92) and sodium's risk elevation (PIP = 0.87); magnesium and calcium emerge as robust protective factors against CKD, while sodium intake increases disease risk. Phosphorus, potassium, zinc, and copper demonstrate potential benefits, whereas iron shows context-dependent effects. These findings emphasize mineral-specific dietary strategies for CKD prevention.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"60-68"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanistic insights and evidence-based management of metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) through combined diet and exercise interventions: an evidence-based narrative review.","authors":"Yuanyuan Chen, Rongqin Liu, Renli Huang, Qinwei Li, Yu Zhang","doi":"10.3164/jcbn.25-259","DOIUrl":"10.3164/jcbn.25-259","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is increasing worldwide, while management is constrained by limited effective pharmacotherapies and poor long-term adherence to lifestyle change. We synthesized mechanistic pathways and primary human interventional evidence on combined diet-plus-exercise strategies to inform lifestyle management. Evidence-based narrative review with a structured literature search and a predefined evidence framework. We prioritized primary human interventional studies (randomized or controlled trials when available) evaluating combined dietary and exercise interventions in MASLD/NAFLD; mechanistic studies were used for biological context. Reviews/meta-analyses were used only to summarize existing evidence and were not treated as additional primary studies. Owing to heterogeneity in interventions and outcomes, we performed qualitative synthesis (no <i>de novo</i> meta-analysis). Evidence indicates that combined dietary and exercise interventions exert synergistic effects on key metabolic and inflammatory pathways, including AMPK/SIRT1 activation, mitochondrial biogenesis, and gut-liver axis modulation, thereby improving hepatic steatosis and metabolic profiles more effectively than single interventions. Integrated dietary and exercise interventions appear more effective than diet- or exercise-only strategies for MASLD/NAFLD management. Individualized programs supported by digital health technologies and multi-omics profiling may further optimize lifestyle intervention delivery and move care toward a precision-oriented model.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"1-14"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effects of lutein, zeaxanthin and anthocyanins supplementation on visual function and vision protection in healthy school-aged children: a single-center prospective randomized controlled study.","authors":"Zixiu Zhou, Pengjie Zheng, Sizhen Li, Qingsong Yang, Shanshan Xu, Na Zhao, Jinshuo Wang, Yuan Shi, Qidong Lu, Zhengyuan Zhou, Annan Xu","doi":"10.3164/jcbn.25-284","DOIUrl":"10.3164/jcbn.25-284","url":null,"abstract":"<p><p>Dietary carotenoids (lutein and zeaxanthin) and anthocyanins show retinal protective potential, yet their clinical efficacy in healthy children's developing visual systems remains unclear. We aimed to investigate whether lutein, zeaxanthin, and anthocyanin (LA) supplementation enhances visual function and vision protection in healthy school-aged children (6-10 years). Sixty-four participants were randomized to control or treatment (received LA supplementation daily) groups. Macular pigment optical density (MPOD), central foveal thickness (CFT), minimum foveal thickness (MFT), axial length (AL), spherical equivalent refraction (SER) and contrast sensitivity function (CSF) after LA supplementation were examined at baseline, 1, 3, and 6 months. ASQ-11 questionnaire was used to evaluate eye fatigue. Compared with control group, from baseline to 1, 3, and 6 months, MPOD levels were increased in treatment group, with the most significant increase at the 6-month follow-up. CFT and MFT levels were also elevated with time. Moreover, AL remarkably increased at 1, 3, and 6 months, considering it is a physiological increase caused by growth and development of children. At 6 months, the change in AL was prominently reduced in the treatment group. Besides, the reduction of SER levels was less in treatment group than that in control group. Additionally, CSF of control group and treatment group increased during the 6-month follow-up. CSF at spatial frequency 3 c/d in the treatment group was markedly higher than that in the control group at the sixth month follow-up. Furthermore, LA notably improved visual fatigue symptoms. Collectively, LA supplementation enhances visual function and vision protection in healthy school-aged children. Registration number (TRN): ChiCTR2500100376.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"52-59"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Zhang, LingYong Kong, TengFei Chen, Chuang Ding
{"title":"Mechanism of enteral nutrition in regulating Tfh/Tfr immune imbalance in colorectal cancer via the TLR4 signaling pathway.","authors":"Ming Zhang, LingYong Kong, TengFei Chen, Chuang Ding","doi":"10.3164/jcbn.25-260","DOIUrl":"10.3164/jcbn.25-260","url":null,"abstract":"<p><p>This study aims to investigate the regulatory effects and underlying mechanisms of enteral nutrition (EN) on colorectal cancer (CRC). An inflammatory colorectal tumor model was established in mice using the azoxymethane-dextran sulfate sodium method. The mice were divided into groups including a model group and groups treated with EN or EN plus the Toll-like receptor 4 (TLR4) activator lipopolysaccharide. The T follicular helper/T follicular regulatory (Tfh/Tfr) cell ratios in splenic tissues were analyzed by flow cytometry. Protein expression related to the TLR4 pathway and cytokines in colonic tissues was assessed by Western blotting and quantitative real-time polymerase chain reaction. Histopathological changes were evaluated using hematoxylin-eosin staining. The proportion of Tfh cells to Tfr cells is significantly imbalanced in CRC, and this imbalance was corrected following EN treatment. This correction of Tfh/Tfr imbalance was found to inhibit tumor growth, suggesting that the regulatory effect of EN on CRC may be mediated through the modulation of the Tfh/Tfr cell balance. At the molecular level, we discovered that EN was found to suppress the activation of the TLR4 signaling pathway. Furthermore, the addition of lipopolysaccharide abolished the effects of EN, indicating that the regulation of the Tfh/Tfr cell ratio by EN is mediated through the TLR4 signaling pathway. This study provides evidence that EN can inhibit the progression of CRC, potentially by regulating Tfh/Tfr immune imbalance via the TLR4 signaling pathway. These findings highlight the potential of EN as a therapeutic strategy for CRC treatment.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"69-75"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of body position on high-resolution manometry parameters and their correlations with symptoms.","authors":"Sayaka Yoshida, Hideki Mori, Tatsuhiro Masaoka, Juntaro Matsuzaki, Kazumi Inokuchi, Hiroko Ando, Takanori Kanai","doi":"10.3164/jcbn.25-282","DOIUrl":"10.3164/jcbn.25-282","url":null,"abstract":"<p><p>High-resolution manometry (HRM) is essential for evaluating esophageal motility, and the Chicago Classification ver. 4.0 recommends measurements in both supine and upright positions. However, the impact of body position on HRM metrics and their relationship with symptoms has not been fully clarified. In this retrospective observational study, 287 patients undergoing HRM were categorized into postoperative, disorders of esophagogastric junction outflow (DEO), peristaltic disorders, and normal motility groups. Integrated relaxation pressure (IRP), distal contractile integral (DCI), and intrabolus pressure (IBP) were assessed in both positions, and symptom severity was evaluated using the Eckardt score, Gastroesophageal Reflux Disease Questionnaire (GerdQ), and Hospital Anxiety and Depression Scale (HADS). IRP and DCI were significantly lower in the upright position, whereas IBP showed no positional difference. In the DEO group, IRP correlated with the Eckardt score in both positions, with a slightly stronger correlation in the supine position. Reflux and anxiety symptoms also correlated with the Eckardt score, suggesting interactions between motility impairment, reflux, and psychological factors. Although HRM metrics varied by position, neither position was clearly superior for explaining symptoms. HRM in both supine and upright positions remains essential for comprehensive clinical assessment.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"97-103"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topical Mongolian <i>Lycium ruthenicum</i> extract attenuates oxidative stress, inflammation, and itch signaling in atopic dermatitis models.","authors":"Himeno Saito, Chizuki Usui, Reo Matsuzaka, Chiharu Ohira, Mao Kaneki, Yoshiichi Takagi, Yoshikazu Hoshino, Tomoki Fukuyama","doi":"10.3164/jcbn.26-41","DOIUrl":"10.3164/jcbn.26-41","url":null,"abstract":"<p><p>Mongolian <i>Lycium ruthenicum</i> (LR) are rich in anthocyanins and oligomeric proanthocyanidins, which possess potent antioxidant and anti-inflammatory properties. However, their therapeutic potential in inflammatory skin diseases, such as atopic dermatitis (AD), remains unclear. This study investigated the antioxidant and anti-inflammatory properties of topical LR extract and its therapeutic potential in experimental models of AD. Antioxidant activity was assessed in UVB-irradiated human keratinocytes (HaCaT) by measuring intracellular reactive oxygen species (ROS) and the expression of Nrf2 and HO-1. Anti-inflammatory effects were examined in TNF-α/IFN-γ-stimulated HaCaT and LPS-induced DC2.4 cells. <i>In vivo</i> efficacy was evaluated in NC/nga and HR-1 mouse models of AD. LR extract significantly suppressed UVB-induced ROS production and enhanced Nrf2 and HO-1 expression. It reduced pro-inflammatory cytokine and chemokine levels by inhibiting ERK phosphorylation in HaCaT cells. Topical LR treatment <i>in vivo</i> attenuated trans-epidermal water loss, epidermal hyperplasia and immune cell infiltration, and Th2 cytokine levels in the lymph nodes. Dorsal root ganglion calcium imaging revealed decreased neuronal responsiveness to pruritogens following LR application. Topical application of LR extract ameliorated AD-like inflammation and pruritus through antioxidative and immunomodulatory mechanisms. These findings highlight LR as a natural therapeutic agent for managing oxidative stress-related skin inflammation and barrier dysfunction.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"111-124"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning identifies neutrophil-related signatures for diagnostic value in neonatal sepsis.","authors":"Qibing Chen, Jiandong Chen, Ronghua Zhong","doi":"10.3164/jcbn.25-270","DOIUrl":"10.3164/jcbn.25-270","url":null,"abstract":"<p><p>Neonatal sepsis (NS) is one of the leading causes of neonatal mortality. The nonspecific clinical manifestations and the limited timeliness of existing biomarkers (such as C-reactive protein) highlight the urgent need for highly accurate diagnostic tools. Neutrophils, as key effector cells of innate immunity, are closely involved in the progression of NS. This study integrated training (GSE69686) and validation (GSE25504) datasets from the GEO database. Neutrophil infiltration characteristics were analyzed utilizing CIBERSORT, and weighted gene co-expression network analysis (WGCNA) was introduced to determine neutrophil-related co-expression modules. Three machine learning algorithms-LASSO, SVM-RFE, and RF-were implemented to cross-screen core diagnostic genes. A combined diagnostic model was distributed based on these genes. NetworkAnalyst was utilized to predict miRNA-TF regulatory networks, and GSVA was conducted to interpret biological functions. Three algorithms identified IL1R2 and METTL7B as core diagnostic genes; the model showed strong reliability. IL1R2 high expression correlated with reduced CD8<sup>+</sup> T cells, regulatory T cells, and neutrophils (<i>p</i><0.05). METTL7B high expression linked positively to B cells and negatively to NK cells/neutrophils. The two genes synergistically cause immune cell dysfunction. Six miRNAs and 15 transcription factors (e.g., NFKB1/RELA, STAT3) regulating these genes were found, involved in inflammation and metabolic reprogramming. Integrating neutrophil infiltration and triple-machine-learning, this study first proposed an IL1R2/METTL7B two-gene panel. The model had high accuracy and generalizability, potentially contributing to NS pathogenesis via immune dysfunction and metabolic reprogramming, supporting rapid diagnostics and targeted interventions.</p>","PeriodicalId":15429,"journal":{"name":"Journal of Clinical Biochemistry and Nutrition","volume":"79 1","pages":"40-51"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}