Biomolecules最新文献

{"title":"Melatonin: Roles and Molecular Mechanisms in Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Binjing Pan, Xiaoyu Lv, Xinyuan Guo, Jingfang Liu","doi":"10.3390/biom16091357","DOIUrl":"10.3390/biom16091357","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic disorder that affects the endocrine and digestive systems. It often leads to multi-system metabolic abnormalities, including disturbances in blood glucose and lipid levels. MASLD ranges from normal liver to steatosis, followed by fibrosis and cirrhosis, eventually leading to hepatocellular carcinoma. This disease can exacerbate liver-related complications and promote the development of extrahepatic diseases in other systems, including the cardiovascular and renal systems. Melatonin, a regulator of neurotransmitters, hormones, and biological responses, modulates oxidative stress, buffers free radicals, influences mitochondrial function, and regulates energy. Therefore, melatonin may serve as a novel adjunctive therapeutic agent for delaying or inhibiting the development of MASLD. We summarize the recent research progress on the effects of melatonin on MASLD and related molecular mechanisms, and identify new ideas and targets for MASLD treatment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic Potato Systemin Enhances <i>Solanum tuberosum</i> Resistance to Potato Virus Y.","authors":"Alexander Skripnikov, Tatiana Suprunova, Michael Taliansky, Natalia O Kalinina","doi":"10.3390/biom16091353","DOIUrl":"10.3390/biom16091353","url":null,"abstract":"<p><p>In recent years, short plant peptides have emerged as highly promising, innovative bioregulators of crop growth and resilience. Activating systemic defense using synthetic plant peptides represents a potent strategy to improve crop resistance against pathogenic threats. Potato virus Y (PVY) causes devastating economic losses in potato (<i>Solanum tuberosum</i>) crops. In this study, we investigated the protective activity of synthetic analogs of systemin, a classic defense peptide originally discovered within the Solanaceae family. We synthesized the putative potato octadecapeptide systemin (AVHSTPPSKRDPPKMQTD) along with two 17-mer variants, each truncated by a single amino acid residue at either the N- or C-terminus, for foliar application. The defensive efficacy of these peptides was evaluated using inoculation and monitoring viral accumulation under controlled growth chamber conditions. Foliar application of all three synthetic peptides significantly reduced the accumulation of the PVY^O ordinary strain over a one-month post-infection period with comparable efficacy. Furthermore, we demonstrated the antiviral effect of the synthetic octadecapeptide against the exceptionally devastating and widespread recombinant PVY^NTN strain. These findings suggest that synthetic derivatives of potato systemin could serve as potential tools for developing eco-friendly antiviral strategies for sustainable crop protection.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Dose Paclitaxel Combined with Dehydrocavidine Synergistically Suppresses Cervical Cancer by Inhibiting FASN/SCD1-Mediated Lipid Metabolism.","authors":"Xuelian Luo, Jin Li, Tianjiao Xing, Shuang Liu, Yiting Deng, Hongxia Xu, Yu Xiao, Hongchen Wang, Xianing Peng, Ying Chen","doi":"10.3390/biom16091354","DOIUrl":"10.3390/biom16091354","url":null,"abstract":"<p><p>Cervical cancer is a leading cause of cancer-related death among women, and acquired resistance to paclitaxel (PTX) frequently results in treatment failure. Dehydrocavidine (DHC), the principal bioactive alkaloid from the traditional Chinese herb <i>Corydalis saxicola</i>, has shown antitumor activity, but its potential in cervical cancer and synergism with PTX remain unknown. We investigated the combined effect of low-dose PTX and DHC in HeLa and SiHa cells and a HeLa xenograft model. ZIP (zero interaction potency) synergy analysis revealed strong synergy in inhibiting proliferation, colony formation, and migration. In vivo, the combination significantly suppressed xenograft tumor growth. Network pharmacology, molecular docking, and experimental validation identified fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) as key targets; the combination downregulated their expression, reducing lipid droplets and triglyceride accumulation. Public single-cell transcriptomic analysis showed elevated FASN/SCD1 in tumor cells and cancer-associated fibroblasts, correlating with poor overall survival. These findings demonstrate that low-dose PTX plus DHC synergistically suppresses cervical cancer by inhibiting FASN/SCD1-mediated lipid metabolism reprogramming, providing a promising strategy to overcome PTX resistance and reduce toxicity.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Effects of Wnt5a-Overexpressing Bone Marrow Mesenchymal Stem Cells on Endothelial Barrier Repair in Acute Lung Injury.","authors":"Shiqi Li, Wanmei He, Manliang Guo, Xintong Yang, Mian Zeng","doi":"10.3390/biom16091356","DOIUrl":"10.3390/biom16091356","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), a common complication of sepsis, is critically characterized by disruption of the alveolar-capillary barrier. The use of mesenchymal stem cells (MSCs) has emerged as a promising therapeutic strategy for ARDS owing to their potent paracrine effects. Wingless-type MMTV integration site family member 5A(Wnt5a) is a secreted protein with context-dependent effects on angiogenesis. This study aimed to investigate whether Wnt5a contributes to bone marrow-derived MSC (BMSC)-mediated repair of endothelial injury and whether Wnt5a-overexpressing BMSCs improve outcomes in an ALI animal model.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) was used to induce endothelial cell (ECs) injury in vitro. EC proliferation, migration, tube formation and permeability, together with the expression of the junctional proteins zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) and the apoptosis-related proteins Bax and Bcl-2, were assessed after coculture with genetically modified BMSCs. In vivo, ALI was induced in mice by intraperitoneal administration of LPS. Lung histopathology, the lung wet-to-dry weight ratio, cytokine concentrations in bronchoalveolar lavage fluid (BALF) and serum, Evans blue extravasation, and the expression of junctional and apoptosis-related proteins were evaluated. PI3K/AKT signaling was examined as a potential pathway associated with the observed effects.</p><p><strong>Results: </strong>Compared with the vector-BMSCs, Wnt5a-overexpressing BMSCs increased the proliferation, migration, and tube formation of LPS-injured ECs; reduced endothelial permeability; preserved junctional protein expression; and shifted apoptosis-related protein expression towards an anti-apoptotic profile. Wnt5a knockdown attenuated these responses. In vivo, treatment with Wnt5a-overexpressing BMSCs was associated with less histological lung injury, lower inflammatory cytokine concentrations and a similar shift in apoptosis-related protein expression after LPS challenge. These protective effects were accompanied by enhanced PI3K/AKT signaling.</p><p><strong>Conclusions: </strong>Wnt5a overexpression optimized the protective effects of BMSCs against ALI in vivo and protected against LPS-induced EC barrier dysfunction in vitro, accompanied by enhanced PI3K/AKT signaling.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein E Mimetic Peptide-Mediated Modulation of Lipid Homeostasis.","authors":"Dilan R Patel, Cole L Martin, G M Anantharamaiah, Stephen G Aller","doi":"10.3390/biom16091352","DOIUrl":"10.3390/biom16091352","url":null,"abstract":"<p><p>Lipid homeostasis is essential for maintaining cellular function and metabolic balance in all organisms, and its dysregulation can contribute to hypercholesterolemia, atherosclerosis, and cardiovascular disease. Adverse health outcomes are associated with elevated levels of low-density lipoprotein cholesterol (LDL-C), retention of which causes macrophages to transition into foam cells, leading to widespread inflammation, cardiovascular disease, and atherosclerosis. Statins (HMG-CoA reductase inhibitors) are considered the gold standard for LDL and very-low-density lipoprotein (VLDL) reduction, yet they exhibit side effects like myalgia and insulin resistance. Apolipoprotein E (apo E)-based lipid-binding synthetic mimetic peptides have been shown to clear cholesterol from the blood through canonical hepatic pathways such as HSPG receptors and are currently being studied to reduce plasma cholesterol. This review examines the development, biological properties, and therapeutic potential of the apo E mimetic peptide AEM-28. AEM-28 reduces atherogenic lipoproteins from plasma efficiently in multiple preclinical models as well as Phase I clinical trials in humans, where general tolerance of the treatment was observed. AEM-28 utilizes a unique mechanism of action that involves binding to atherogenic lipoproteins with multiple receptor-binding domains, facilitating enhanced clearance via the highly abundant heparan sulfate proteoglycans on hepatocytes. These attributes support the potential of AEM-28 as a complementary therapeutic or even an alternative for patients requiring LDL apheresis and those with hypercholesterolemia, atherosclerosis, or cardiovascular disease.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salivary Versus Circulating Insulin in Humans: Quantitative Evidence and Validation Requirements.","authors":"Lorenzo Albanese","doi":"10.3390/biom16091348","DOIUrl":"10.3390/biom16091348","url":null,"abstract":"<p><p>Salivary insulin offers a non-invasive approach to repeated metabolic assessment, but its quantitative relationship with circulating insulin remains incompletely defined. Paired human evidence was critically examined across the domains of cross-matrix association, temporal correspondence, scale, quantitative mapping, agreement, validation, and transferability. Salivary insulin tracked serum or plasma insulin under defined fasting and dynamic conditions, although association strength, temporal correspondence, and saliva-to-blood scale varied across populations, metabolic states, protocols, and salivary measurands. The available paired human evidence includes one explicit saliva-to-plasma mapping equation. Calibration, direct individual-level agreement, and independent external validation of a fixed mapping were not demonstrated, and individual prediction error was not characterized. Current evidence therefore supports salivary insulin as a context-dependent indicator of circulating insulin dynamics rather than a generally transferable quantitative substitute for serum or plasma insulin. Progression toward quantitative use requires explicit definition of the target measurand and temporal relationship, adequate analytical validation, calibration, characterization of individual prediction error, agreement assessment when quantitative substitution is intended, and independent external validation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dystrophin Deficiency Creates a Pro-Ferroptotic Environment in Diaphragm of mdx Mice That Is Modified by Diet and Glucocorticoid Treatment.","authors":"Morgan E Vorwald, Melissa Roths, Rudy J Valentine, Joshua T Selsby","doi":"10.3390/biom16091347","DOIUrl":"10.3390/biom16091347","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting with altered iron homeostasis and dysregulated lipid metabolism. Insulin resistance and obesity are common in DMD, but their impact on disease progression, particularly during glucocorticoid (GC) treatment, remains unclear. The role of ferroptosis, iron-dependent cell death, in DMD muscle pathology remains uncertain. We hypothesized that ferroptotic signaling would increase in mdx skeletal muscle, be further exacerbated by a high-fat, high-sucrose diet (HFHSD), and be attenuated by GC treatment. Male C57 and mdx mice were fed a control diet or HFHSD, with or without prednisolone, for 19 weeks before diaphragm western blot analysis. Dystrophic diaphragms had an increased abundance of transferrin (131%, <i>p</i> = 0.0006), transferrin receptor (72%, <i>p</i> = 0.0041), ferritin heavy chain (281%, <i>p</i> < 0.0001), acyl-CoA synthetase long-chain family member 4 (36%, <i>p</i> = 0.0080), and 5-lipoxygenase (101%, <i>p</i> = 0.0016) compared with C57. Despite these pro-ferroptotic changes, malondialdehyde and 4-hydroxynonenal were unchanged. Glutathione peroxidase 4 was robustly increased (800%, <i>p</i> < 0.0001), suggesting maintenance of redox balance and suppression of ferroptotic death. The HFHSD did not exacerbate ferroptotic signaling, whereas GC treatment partially offset disease-related changes in iron-handling and antioxidant proteins. These findings indicate that dystrophic diaphragms experience ferroptotic stress that is actively constrained, likely by compensatory GPX4 changes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPLUNC1/BPIFA1 Restrains Neutrophil-Dominant Inflammation and Coordinated Inflammatory Gene Programs During LPS-Induced Lung Injury.","authors":"Hexin Lu, Yuanpu Peter Di","doi":"10.3390/biom16091349","DOIUrl":"10.3390/biom16091349","url":null,"abstract":"<p><p>Acute lung injury (ALI) is characterized by alveolar-capillary barrier disruption, increased pulmonary permeability, impaired gas exchange, and inflammation. Lipopolysaccharide (LPS), a potent microbial trigger of inflammation, is widely used to model ALI. Short palate, lung, and nasal epithelial clone 1 (SPLUNC1), also known as BPIFA1, is an abundant surfactant-like protein secreted by the airway epithelium with antimicrobial and immunomodulatory functions. However, its role in endotoxin-induced lung injury remains incompletely understood. We compared pulmonary responses to LPS in wild-type and SPLUNC1/BPIFA1-knockout mice. Mice received intranasal PBS or 5 μg LPS were evaluated 24 h later by bronchoalveolar lavage, histology, cytospin, flow cytometry, qPCR, ELISA, and whole-lung RNA sequencing. Compared with WT mice, LPS-challenged KO mice exhibited greater inflammatory-cell accumulation, enhanced neutrophil recruitment, increased cytokine and chemokine expression, and greater histologic lung injury. Transcriptomic analyses showed preferential activation of TNFα/NF-κB, IL-6-JAK-STAT3, complement, cytokine/chemokine, myeloid/neutrophil, and stress-response in KO lungs. These findings identify SPLUNC1/BPIFA1 as an epithelial-derived regulator that restrains endotoxin-induced inflammatory signaling, neutrophil recruitment, and tissue injury. Collectively, these results support a protective role for SPLUNC1/BPIFA1 in acute pulmonary inflammation and provide a rationale for investigating SPLUNC1/BPIFA1 augmentation to mitigate ALI. Further studies evaluating SPLUNC1-based interventions in preclinical models are warranted.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Recanalization: Neurovascular Unit Protection and Precision Adjunctive Therapy for Ischemic Stroke in the Reperfusion Era.","authors":"Xusheng Wu, Yue Xing, Jing Ma, Xianhui Wang, Xingjiang Xiong","doi":"10.3390/biom16091346","DOIUrl":"10.3390/biom16091346","url":null,"abstract":"<p><p>Intravenous thrombolysis and endovascular thrombectomy (EVT) have increased large-vessel recanalization in acute ischemic stroke, yet macrovascular reopening does not ensure tissue reperfusion or functional recovery. Microvascular no-reflow, blood-brain barrier failure, oxidative injury, thromboinflammation, edema, and hemorrhagic transformation sustain a recanalization-to-recovery gap. Classical neuroprotection failed because of mismatches in models, timing, brain exposure, patient selection, and endpoints, and because ischemic injury was reduced to a single neuronal pathway. Cerebroprotection in the reperfusion era should target the neurovascular unit: delaying penumbral collapse before recanalization, limiting oxidative and vascular injury during thrombectomy, and restoring microcirculatory and barrier function afterwards. Recent trials show a differentiated landscape. ESCAPE-NEXT and RODIN were neutral; TASTE-2 suggested a borderline overall effect and imaging-defined heterogeneity for edaravone dexborneol; BAST supported potential benefit from butylphthalide; and the positive EMPHASIS trial contrasted with neutral EVT-specific MIST-A findings for minocycline. We organize mechanisms and interventions along the macrovascular recanalization-tissue reperfusion-neurovascular-unit preservation-functional recovery continuum, stratify evidence across pharmacological, physiological, delivery, natural-product, and cell/extracellular-vesicle strategies, and propose a precision framework integrating tissue and target windows, reperfusion status, and measurable treatment response. Next-generation trials should combine target engagement, imaging enrichment, prespecified biomarker interactions, and adaptive designs. Current evidence supports redesigning cerebroprotection, not adopting any candidate as a universal adjunct to reperfusion.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Inflammatory Biomarkers in Chronic Autoimmune-Associated Epilepsy: An Exploratory Case-Control Study.","authors":"Laura Serrano-Aguilar, Cristina Fernandez-Hombrados, Mercedes Jimenez-Vargas, Yolanda López-Moreno, Guillermina García-Martín, Pablo Cabezudo-García, Nicolas Lundahl Ciano-Petersen, Guillermo Estivill-Torrús, Manuel Narváez-Peláez, Maria José Aguilar-Castillo, Virgilio Hernándo-Requejo, Pedro Jesus Serrano-Castro","doi":"10.3390/biom16091350","DOIUrl":"10.3390/biom16091350","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune-associated epilepsy (AAE) was recognized by the ILAE in 2017 as a distinct etiological category driven by chronic neuroinflammation rather than structural or genetic mechanisms. Reliable peripheral circulating inflammatory biomarkers to distinguish AAE from structural epilepsy remain lacking, potentially limiting timely recognition and evaluation for immunotherapy. In this observational case-control exploratory single-center study, plasma levels of 20 pro-inflammatory and 3 anti-inflammatory biomarkers, plus cerebrospinal fluid neurofilament light chain and HMGB1, were measured in 18 AAE patients, 33 non-autoimmune epilepsy patients and 16 healthy controls. AAE was defined using Dubey's APE2-based criteria. Univariate comparisons, ROC analysis, and binary logistic regression were performed.</p><p><strong>Results: </strong>Among the 25 biomarkers analyzed, plasma IL-12 showed the lowest nominal <i>p</i>-value in the global between-group comparison (p=0.038), with lower concentrations in AAE. However, no biomarker remained statistically significant after Benjamini-Hochberg false discovery rate correction (IL-12 q=0.366). ROC analysis yielded an AUC of 0.670 for IL-12 alone for distinguishing AAE from the remainder of the cohort. In an exploratory primary multivariable model including plasma IL-12, drug-resistant epilepsy (DRE) status, and EEG pattern, the apparent in-sample discriminative performance was higher than that of IL-12 alone (AUC = 0.771; 95% CI, 0.635-0.892).</p><p><strong>Discussion: </strong>Lower plasma IL-12 levels may reflect a peripheral immune association in chronic AAE. These findings are exploratory and hypothesis-generating and require replication in larger, prospectively recruited, independent cohorts.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}