Cell Biochemistry and Biophysics最新文献

{"title":"Second-Generation Combined Oral Contraceptives Induce Early Cardiovascular Risk Through Inflammatory and Oxidative Vascular Remodeling.","authors":"M O Allen, S A Salami, O M Olumide, O A Lawal-Bamidele, B A Murtala","doi":"10.1007/s12013-026-02191-0","DOIUrl":"https://doi.org/10.1007/s12013-026-02191-0","url":null,"abstract":"<p><p>Second-generation combined oral contraceptive pills (COCPs), particularly formulations containing ethinylestradiol and levonorgestrel, remain widely used because of their effectiveness and affordability in middle and low-income countries. However, concerns persist about their cardiovascular safety. This study investigated the dose-dependent effects of a second-generation COCP on systolic blood pressure (SBP), inflammatory biomarkers, oxidative stress, vascular mediators, and vascular histology in female Sprague-Dawley rats. Twenty-four female Sprague-Dawley rats were acclimatized and randomly assigned to control, low-dose (1.1 µg/kg/day), and high-dose COCP (11 µg/kg/day) groups. Treatments were administered orally for six weeks. SBP and body weight were monitored before and after treatment. Serum C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), and lipid profile were measured. Renal vascular homogenates were analyzed for nuclear factor kappa B (NF-κB), endothelin-1 (ET-1), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase, catalase (CAT), and glutathione. Histological examination was performed on the renal and thoracic arteries. The SBP increased by 4.6% in the low dose and 21.8% in the high dose (p < 0.05). High-dose treatment significantly increased CRP, TNF-α, and NF-κB levels, indicating enhanced systemic and vascular inflammation. Vascular MDA and CAT increased in both treated groups, suggesting oxidative stress with compensatory antioxidant activation. Low-dose COCP increased ET-1 levels, while the NO and lipid profiles showed no significant changes across the treated groups. Both doses produced marked structural alterations in the renal and thoracic arteries. The dose-dependent rise in vascular inflammation, oxidative stress, and SBP suggests early cardiovascular risk is mediated primarily by inflammatory vascular remodeling rather than by overt dyslipidemia.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent Immunometabolic Regulatory Networks Mediated by FOXO3 During Musculoskeletal Aging: Implications for Tissue-Adapted Precision Therapeutics.","authors":"Peng Zhang, Xiao Wang, Xiaotao Shi, Yanhao Yuan, Peizhao Wang, Renkun Zhao, Dongdong Xie, Honglüe Tan, Guorui Cao","doi":"10.1007/s12013-026-02212-y","DOIUrl":"https://doi.org/10.1007/s12013-026-02212-y","url":null,"abstract":"<p><p>Musculoskeletal aging exhibits prominent tissue heterogeneity. Forkhead box O3 (FOXO3) acts as a master transcription factor orchestrating aging, metabolism and immune homeostasis. Existing mechanistic investigations are largely restricted to single tissues, and a head-to-head comparison of FOXO3-governed immunometabolic regulatory networks between knee osteoarthritis (KOA) synovium and aged skeletal muscle remains absent. A retrospective multi-cohort transcriptomic analysis was performed using datasets retrieved from the Gene Expression Omnibus (GEO) database. Two KOA synovial cohorts (GSE55235 and GSE55457, n = 40) and two aged skeletal muscle cohorts (GSE28422 and GSE25941, n = 146) were enrolled, covering a total of 186 tissue samples. We integrated differential expression analysis, random-effects meta-analysis, receiver operating characteristic (ROC) performance evaluation, single-sample gene set enrichment analysis (ssGSEA), and partial correlation analysis adjusted for disease confounding effects. A bootstrap-scoring system was further established to prioritize candidate therapeutic strategies. FOXO3 exhibited opposing expression patterns: it was downregulated in KOA synovium yet upregulated in aged skeletal muscle. The coupling profiles between FOXO3 and immune or metabolic pathways displayed striking tissue-specific divergence. In KOA synovium, FOXO3 expression was positively correlated with mitochondrial energy metabolism and macrophage infiltration, accompanied by selective inflammatory immune infiltration. By contrast, aged skeletal muscle resided in an immune-quiescent microenvironment, where elevated FOXO3 was strongly negatively coupled to oxidative metabolic pathways. Distinct intervention strategies were derived from these divergent network signatures: combined FOXO3 activation and metabolic modulation was recommended for KOA, whereas supplementation with nicotinamide adenine dinucleotide (NAD⁺) precursors constituted the primary intervention for aged skeletal muscle. Opposite FOXO3 expression levels correspond to fundamentally distinct immunometabolic network landscapes during musculoskeletal aging. The functional output of FOXO3 is dictated by the tissue microenvironment rather than its transcriptional abundance alone. This study supports stratified precision geriatric interventions via tissue-specific modulation of the FOXO3 pathway across divergent musculoskeletal aging contexts.Clinical trial number: Not applicable.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"siRNA-Mediated RNF213 Depletion Aggravates Inflammatory Hypoxia-Induced Endothelial Dysfunction and Alters Endothelial-Smooth-Muscle Communication in an In Vitro Model Relevant to Moyamoya Disease.","authors":"Tao Gao, Liming Zhao, Li Wang, Ziqiang Liu, Chaoyue Li","doi":"10.1007/s12013-026-02210-0","DOIUrl":"https://doi.org/10.1007/s12013-026-02210-0","url":null,"abstract":"<p><p>Moyamoya disease is a progressive cerebrovascular disorder associated with variants in ring finger protein 213 (RNF213), endothelial dysfunction and pathological arterial remodelling. However, the relationship between reduced RNF213 abundance, inflammatory hypoxia and endothelial-smooth-muscle communication remains incompletely understood. This study investigated the effects of small interfering RNA (siRNA)-mediated RNF213 depletion in primary human brain microvascular endothelial cells exposed to combined hypoxia, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). Endothelial viability, proliferation, apoptosis, migration, angiogenic network formation and barrier integrity were evaluated. Conditioned-medium and indirect co-culture systems were subsequently used to examine responses in primary human brain vascular smooth muscle cells. Combined RNF213 depletion and inflammatory hypoxia reduced endothelial viability and proliferation, increased apoptosis, impaired migration and network formation, and compromised barrier integrity. Barrier impairment was demonstrated by decreased transendothelial electrical resistance, increased dextran permeability and disruption of vascular endothelial cadherin (VE-cadherin), zonula occludens-1 (ZO-1), claudin-5 and occludin. RNF213 depletion also enhanced endothelial inflammatory activation. Conditioned medium from RNF213-depleted inflammatory-hypoxic endothelial cells was associated with increased smooth-muscle-cell proliferation, migration and colony formation. These responses were accompanied by reduced contractile-marker expression and increased secreted phosphoprotein 1 (SPP1), Krüppel-like factor 4 (KLF4), fibronectin 1 (FN1) and matrix metalloproteinase 9 (MMP9), consistent with transition toward a synthetic, matrix-remodelling phenotype. The responsible endothelial-derived mediator or combination of mediators was not identified. Selected findings were reproduced using indirect co-culture and an independent siRNA targeting a different RNF213 sequence. These findings support an association between siRNA-mediated RNF213 depletion, endothelial stress susceptibility and altered endothelial-smooth-muscle communication in an in-vitro model relevant to Moyamoya disease. RNF213 re-expression or orthogonal genetic validation will be required to establish RNF213-specific causality.Clinical Trial Number None.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network (Cross‑Pathway) Engineered Organization: A Testable Framework for Configuring Regenerative Signalling in the Hair Follicle Niche.","authors":"Rinky Kapoor, Varad Rajendra Saptarshi, Raji Patil, Debraj Shome","doi":"10.1007/s12013-026-02208-8","DOIUrl":"https://doi.org/10.1007/s12013-026-02208-8","url":null,"abstract":"<p><p>Hair follicle regeneration is commonly interpreted through individual pathways, cell populations, or classes of pro-growth interventions. Although these approaches have established the importance of hair follicle stem cells, dermal papilla cells, immune populations, extracellular matrix, and vascular-lymphatic niches, they provide limited guidance for how multiple regenerative inputs should be configured when designing an intervention. We propose Network (Cross‑Pathway) Engineered Organization as a translational design framework rather than as a replacement for established hair follicle niche biology. The framework defines an intervention through four linked, experimentally manipulable dimensions: composition, topology, temporal structure, and coupling. The framework predicts that interventions matched for total signal exposure may generate distinct regenerative outcomes when their architectural configuration differs. It further proposes that clinic-based induction and home-based maintenance can be studied as temporally coupled components of a single protocol-level signalling configuration. The framework is falsifiable if manipulating signal ratio, localization, sequencing, or kinetics does not alter molecular, cellular, or phenotypic outcomes after total dose and baseline niche state are controlled. By specifying intervention variables, comparators, and testable predictions, this article connects descriptive hair follicle biology with experimentally tractable design principles for regenerative biology.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicted Molecular Interactions of Selected Trifolium Pratense L. Phytochemicals with H-Ras p21 Protein.","authors":"Faik Gökalp, Ramazan Erenler","doi":"10.1007/s12013-026-02195-w","DOIUrl":"https://doi.org/10.1007/s12013-026-02195-w","url":null,"abstract":"<p><p>Members of the Fabaceae (Leguminosae) family are widely distributed flowering plants with considerable agricultural and pharmacological importance. Among them, Trifolium pratense L. is recognized as a rich source of bioactive phytochemicals, particularly isoflavones such as biochanin A and formononetin, as well as phenolic acids including caffeic, rosmarinic, and chlorogenic acids. These compounds have been associated with antioxidant, anti-inflammatory, and potential anticancer-related biological activities in previous studies. In the present study, selected phytochemicals reported from Trifolium pratense L. were evaluated for their predicted molecular interactions with the H-Ras p21 protein by using molecular docking analysis. The crystal structure of the target protein (Pdb id: 5P21) was obtained from the Protein Data Bank, and docking simulations were performed to estimate binding affinity and possible interaction profiles of the selected ligands. The antioxidant activity data were included to support the biological relevance of the investigated phytochemicals. The computational findings suggest that several compounds from Trifolium pratense L. may exhibit favorable binding interactions with H-Ras p21 protein. However, these results represent preliminary in silico predictions and do not directly indicate therapeutic efficacy or inhibitory activity. Therefore, further experimental validation, including in vitro and in vivo studies, is required to confirm the biological significance of these interactions. This study contributes to the growing literature on plant-derived bioactive compounds and their potential applications in computational cancer research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Anticancer Activities of Rhodiola rosea L. Extracts in Breast Tumor Cells: Phenotype Changes and Potential Mechanisms of Action.","authors":"Sugandh Singh, Anita Kumari, Bramanandam Manavathi","doi":"10.1007/s12013-026-02198-7","DOIUrl":"https://doi.org/10.1007/s12013-026-02198-7","url":null,"abstract":"<p><p>Rhodiola rosea L., a medicinal plant native to the high-altitude regions of the Indian Himalayas, contains diverse bioactive phytochemicals with broad pharmacological activities. This study investigated the anticancer activity and associated molecular responses of R. rosea root extracts in human breast cancer models. Commercial Rhodiola rosea root powder reconstituted in different solvents was evaluated for cytotoxicity against SK-BR-3, MDA-MB-231, and MCF-7 breast cancer cells, with HEK-293 cells serving as a non-malignant human reference model. The extracts exhibited concentration- and time-dependent cytotoxic effects, with differential sensitivity among breast cancer subtypes. MDA-MB-231 cells were subsequently selected for mechanistic investigations. Scratch wound-healing assays demonstrated reduced cell migration following extract treatment, accompanied by decreased expression of epithelial-mesenchymal transition (EMT)-associated proteins, including Snail, Slug, Vimentin, and N-Cadherin. Flow-cytometric analysis revealed extract-dependent redistribution of cells across the G0/G1, S, and G2/M phases, with dimethyl sulfoxide (DMSO)-solubilized R. rosea extract (RRD) and methanol-solubilized R. rosea extract (RRM) increasing the G0/G1 population and reducing the G2/M population, whereas ethanol-solubilized R. rosea extract (RRE) produced a distinct cell-cycle response. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) profiling identified diverse phytochemical constituents in the extracts. Western blot analysis further demonstrated modulation of proteins involved in proliferation, cell-cycle regulation, apoptosis, tumor suppression, and EMT, including reduced hematopoietic PBX-interacting protein (HPIP)/protein kinase B (AKT) signaling, cellular myelocytomatosis oncogene (c-Myc), Cyclin A, Cyclin B, Fibrillarin (FBL), Aurora B, Snail, and Slug, together with increased phosphatase and tensin homolog (PTEN), phosphorylated retinoblastoma protein (pRb), AMP-activated protein kinase (AMPK), and cleaved Caspase-3. Collectively, these findings indicate that R. rosea extracts exert multifaceted anticancer effects through modulation of proliferative signaling, cell-cycle progression, apoptotic responses, and EMT-associated phenotypic changes.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Activity and Molecular Docking Analysis of Trans-Cinnamic Acid in Human Lung Cancer.","authors":"Ebru Nur Dursun, Sedef Akçaalan, Canan Eroğlu Güneş, Seda Şirin, Serap Niğdelioğlu Dolanbay, Ercan Kurar","doi":"10.1007/s12013-026-02203-z","DOIUrl":"https://doi.org/10.1007/s12013-026-02203-z","url":null,"abstract":"<p><p>Lung cancer is known to have a very high incidence and mortality rate. Trans-cinnamic acid (tCA) is a phenolic compound found in various fruits and vegetables and is known to have many effects such as antimicrobial, anti-inflammatory and anticancer. In this study, molecular docking analysis was performed to predict the binding affinities of tCA toward apoptosis- and ER stress-related target proteins. The effects of tCA on proliferation, apoptosis and endoplasmic reticulum (ER) stress gene expression, colony forming ability, total antioxidant status (TAS) and total oxidant status (TOS) in A549 human lung cancer cells were investigated. Cell proliferation and, expression levels of genes associated with apoptosis and ER stress determined using XTT and qRT-PCR, respectively. ELISA test was used for TAS, TOS and caspase-3 levels. Molecular docking analysis predicted favorable binding affinities of tCA toward the investigated target proteins. The IC₅₀ value of tCA in A549 cells was found to be 2.59 mM at 48 h. Treatment with tCA significantly increased the expression of apoptosis genes including BAX, CASP3, CASP7, CASP8, CASP9, CYCS, and FADD. Among the ER stress-associated genes analyzed, only PERK and CHOP showed significant upregulation following tCA treatment, while no significant changes were observed in the remaining ER stress-related genes. Furthermore, tCA treatment caused a decrease in TAS level but an increase in TOS level. tCA suppressed the ability to form colonies in A549 cells according to the colony assay. In conclusion, tCA inhibited proliferation and colony formation, modulated selected apoptosis- and ER stress-related genes, and altered oxidative stress parameters in A549 cells. These in vitro findings provide preliminary evidence supporting the potential anticancer activity of tCA; however, further protein-level, functional, and in vivo studies are required to confirm the underlying mechanisms and therapeutic potential. The image outlines a study evaluating the anticancer effects of trans-cinnamic acid (tCA) on A549 lung cancer cells. Molecular docking analysis showed tCA has potential binding affinity to target proteins. In cell experiments, the IC50 of tCA was 2.59 mM at 48 h, determined by an XTT test. Treatment with tCA reduced TAS and caspase-3 levels while increasing TOS. RNA isolation and cDNA synthesis were followed by quantitative RT-PCR analysis, indicating that tCA may induce upregulation of ER stress and apoptotic markers in A549 cells. A colony assay demonstrated that tCA suppressed colony formation in these cells. ELISA assays for TAS, TOS, and caspase-3 were also performed as part of the analysis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting the Role of IRF1 in Oxidized Mitochondrial DNA-Driven PANoptosis.","authors":"Güney Sarıoğlu","doi":"10.1007/s12013-026-02204-y","DOIUrl":"https://doi.org/10.1007/s12013-026-02204-y","url":null,"abstract":"<p><p>Zhang et al. proposed that interferon regulatory factor 1 (IRF1) mediates sensing of oxidized mitochondrial DNA (ox-mtDNA) and promotes macrophage PANoptosis during lung ischemia-reperfusion injury. Their findings provide important mechanistic and translational insights into mitochondrial damage-driven inflammatory cell death. This letter highlights a key distinction between demonstrating that IRF1 is functionally required downstream of ox-mtDNA release and establishing IRF1 as a direct nucleic-acid sensor. IRF1 is primarily characterized as a transcription factor, whereas cytosolic mitochondrial DNA is generally recognized through established nucleic-acid sensing pathways, including cGAS-STING and, depending on cellular localization, TLR9. The available evidence therefore supports IRF1 as a critical downstream mediator of ox-mtDNA-associated signaling rather than conclusively identifying it as the proximal molecular sensor. Further experiments assessing canonical DNA-sensing pathways and direct IRF1-DNA interactions may clarify the molecular ordering of this pathway and refine its therapeutic implications in lung ischemia-reperfusion injury.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polydatin Attenuates Isoproterenol Induced Cardiac Hypertrophy in Association with Reduced Oxidative Stress, NOX2 Subunit Expression, and CaMKII-MEF2C Signaling.","authors":"Bilge Eren Yamasan, Mustafa Yıldız, Onur Ersoy, Selçuk Korkmaz, Ruhan Deniz Topuz, Orkide Palabıyık","doi":"10.1007/s12013-026-02209-7","DOIUrl":"https://doi.org/10.1007/s12013-026-02209-7","url":null,"abstract":"<p><p>Pathological cardiac hypertrophy induced by chronic β-adrenergic receptor (β-AR) stimulation contributes to adverse cardiac remodeling and the progression of heart failure, with NADPH oxidase (NOX2)-derived reactive oxygen species (ROS) acting as key mediators of redox-dependent hypertrophic signaling. Sustained ROS generation can promote oxidative activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and downstream myocyte enhancer factor 2 C (MEF2C)-mediated transcriptional reprogramming. Polydatin, a natural glucoside of resveratrol, has been reported to exert antioxidant and cardioprotective effects. However, its influence on the NOX2-ROS-CaMKII-MEF2C axis under chronic β-AR stimulation remains unclear. In the present study, male Wistar rats were assigned to control, isoproterenol (5 mg/kg/day, subcutaneous, 4 weeks), or isoproterenol + polydatin (100 mg/kg/day, oral gavage) groups. Cardiac hypertrophy was evaluated by morphometric indices, ANP and BNP mRNA expression levels, and histological analyses. Oxidative stress was assessed through NADH oxidase activity, protein carbonyl content, and total antioxidant status. Protein expression of NOX2 subunits (gp91phox, p22phox, p47phox, p67phox, p40phox) and components of the CaMKII-MEF2C pathway were determined by Western blot and reverse transcription quantitative PCR (RT-qPCR). Isoproterenol administration induced marked cardiac hypertrophy, elevated oxidative stress markers, increased expression of NOX2 regulatory subunits, and activated the CaMKII-MEF2C pathway. Polydatin treatment significantly attenuated hypertrophic indices, reduced NADH oxidase activity and protein carbonyl levels, restored antioxidant capacity, and suppressed p47phox, p67phox, p40phox expression along with p-CaMKII^Thr286/CaMKII, ox-CaMKII/CaMKII ratios and MEF2C expression. These findings suggest that the attenuation of isoproterenol induced cardiac hypertrophy by polydatin is associated with modulation of oxidative stress, NOX2 subunit expression, and CaMKII-MEF2C signaling, although a causal role of this pathway remains to be established.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Approach Investigating Differentially Expressed Genes Associated With Parkinson's Disease on Exposure to Pesticides Through Nutritional Uptake.","authors":"Navya Ramachandran, Bianca Maria Lewis, Apoorva Prashanth, Arun Kumar A, Sasmita Sabat","doi":"10.1007/s12013-026-02206-w","DOIUrl":"https://doi.org/10.1007/s12013-026-02206-w","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a multifactorial neurodegenerative disease, with environmental exposures such as pesticides implicated as contributing risk factors. While ensemble machine learning (ML) models have shown promise in identifying discriminating genes from transcriptomic data, their generalizability across heterogeneous toxicogenomic datasets remains poorly characterized. Here, we present a robust statistical pipeline as the primary framework for identifying PD-associated, pesticide-responsive differentially expressed genes (DEGs), developed in direct response to the limitations observed in an ensemble ML approach. The ensemble model, combining individual ML models, Random Forest, Logistic Regression and Gradient Boosting was first trained on merged GEO transcriptomic datasets following normalization and feature selection (SelectKBest, ANOVA F-test, StandardScaler). Initially, an ROC AUC (Receiver Operating Characteristic Area Under the Curve) of 0.734 with a cross-validation (CV) AUC of 0.632 was obtained with an average AUC of 0.806 +/- 0.106 across 10 different splits of train/test data points. The confusion matrix and PCA plots indicated the presence of strong batching effects driving these results. Batch correction improved CV AUC to 0.864 ± 0.142, yet cross-dataset validation collapsed to an ROC AUC of 0.523 ± 0.040, with the model consistently predicting a single class-indicating the ensemble had learned technical artefacts rather than generalizable biological signal. Given this failure of ML generalizability, an alternate, statistically grounded pipeline was developed that relied on domain-specific analysis of transcriptomics data. Differential expression was assessed using limma to determine the extent and significance of gene expression changes across pesticide-exposure datasets. Hub genes were identified through protein-protein interaction network analysis, and their associated pathways were enriched and validated against existing literature. The protein-protein interaction network was constructed and hub genes {Citation}with their respective pathways were identified. The fact that pesticides contribute to the progression of PD has been established by multiple studies. This study highlights the necessity of statistically rigorous, domain-informed approaches over black-box ML methods for identifying reliable, biologically meaningful DEGs-representing a novel methodological comparison not previously explored in pesticide-associated PD biomarker research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149260279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}