Biochemistry and Biophysics Reports最新文献

{"title":"CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system","authors":"Jiafang Cui,&nbsp;Ling Shen,&nbsp;Bing Han","doi":"10.1016/j.bbrep.2025.102394","DOIUrl":"10.1016/j.bbrep.2025.102394","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) are a class of covalently closed, non-coding RNA molecules characterized by their exceptional stability and tissue-specific expression. Once considered splicing artifacts, they have emerged as pivotal regulators in cellular pathophysiology, particularly within the central nervous system (CNS), where they are highly abundant. This review synthesizes the current understanding of the biogenesis, molecular functions, and regulatory roles of circRNAs in major CNS disorders, underscores their significant potential as next-generation diagnostic and prognostic biomarkers, as well as promising therapeutic targets. Moving from bench to bedside, the review critically examines the burgeoning landscape of circRNA-based therapeutics. We assess the promise and limitations of current delivery platforms, including exosomes and lipid nanoparticles (LNPs), with special attention to the formidable challenge of traversing the blood-brain barrier (BBB). To conclude, we outline the prevailing challenges and future perspectives, emphasizing that the development of more sensitive detection methods and optimized delivery systems is paramount to translating the immense potential of circRNAs into tangible clinical solutions for CNS diseases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102394"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune overactivation hinders nuclear reprogramming through IFN-IFNAR1 axis","authors":"Zhimin Song ,&nbsp;Yaofeng Wang ,&nbsp;Yun Zhang ,&nbsp;Jingjing Chen ,&nbsp;Tinghong Zhang ,&nbsp;Shu Meng","doi":"10.1016/j.bbrep.2025.102395","DOIUrl":"10.1016/j.bbrep.2025.102395","url":null,"abstract":"<div><div>Nuclear reprogramming to pluripotency holds great promise for regenerative medicine. However, innate immune overactivation may impair nuclear reprogramming efficiency but the underlying mechanism is not fully understood. Here we used mouse embryonic fibroblasts isolated from doxycycline-inducible OSKM transgenic mice as the nuclear reprogramming system and administered a high dosage of Polyinosinic polycytidylic acid (PIC) to stimulate TLR3 as the innate immune overactivation. PIC treatment reduced nuclear reprogramming efficiency. We identified that PIC treatment upregulated type I interferon transcription and secretion, IFNAR1 cell surface expression, and nuclear Stat1 level. Importantly, the introduction of Ifnar1 blocking antibody completely reversed this impaired nuclear reprogramming efficiency. Similarly, Ifn-β neutralizing antibody substantially ameliorated the impaired nuclear reprogramming efficiency caused by PIC treatment. Our data suggest that innate immune overactivation impairs nuclear reprogramming through the IFN-IFNAR1 axis. Blocking this signaling pathway can be used as a general strategy to enhance nuclear reprogramming efficiency.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102395"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation","authors":"Panjiao Pang,&nbsp;Mingyang Yu,&nbsp;Huixin Ma,&nbsp;Longkai Wei,&nbsp;Jiali Huang,&nbsp;Lingxin Zhao,&nbsp;Ying-hua Zhang","doi":"10.1016/j.bbrep.2026.102464","DOIUrl":"10.1016/j.bbrep.2026.102464","url":null,"abstract":"<div><div>The localization and translation of mRNAs play crucial roles in maintaining cellular phenotype and function, with RNA-binding protein (RBP) contributing significantly to these processes. TAR DNA-binding protein of 43 kDa (TDP-43) is an RNA/DNA-binding protein that is primarily localized in the nucleus, where it performs essential functions in pre-mRNA splicing, mRNA transport, and the stabilization and localized translation of mRNA. Its mis-localization from the cytoplasm, as well as mutations, protein misfolding, and posttranslational modifications, is closely linked to a reduction in its RNA-binding ability. This functional impairment is implicated in the initiation and progression of neurodegenerative diseases and cancer. In this review, we begin with a retrospective analysis of the molecular mechanism by which distinct domains of TDP-43 contribute to the initiation and progression of disease, particularly because its overexpression in tumors significantly influences disease progression. We subsequently elucidate the classical mechanisms of mRNA localization and translation, while clarifying the role of TDP-43 in these processes. Finally, we summarize the mechanisms by which TDP-43 facilitates the formation of ribonucleoprotein particles and this protein's involvement in mRNA localization and translation, as well as its associated molecular pathways. In conclusion, this review highlights the critical roles of TDP-43 and subsequent therapeutic strategies for treatment of neurodegenerative diseases and tumors.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102464"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of machine learning-based methods in cancer classification using microRNA","authors":"Zeinab Tariri ,&nbsp;Mehdi Goodarzi ,&nbsp;Atieh Nouralishahi ,&nbsp;Malihe Sagheb Ray Shirazi ,&nbsp;Meysam Mohammadikhah ,&nbsp;Azita Sadeghzade ,&nbsp;Hossein Gandomkar ,&nbsp;Ehsan Maghrebi-Ghojogh","doi":"10.1016/j.bbrep.2026.102506","DOIUrl":"10.1016/j.bbrep.2026.102506","url":null,"abstract":"<div><div>Early detection and accurate classification of cancer are crucial to improving patient outcomes. Diagnosis and classification of tumors using conventional methods remains challenging. MicroRNAs (miRNAs) are potential biomarkers for accurate tumor classification and differentiation of tumor subtypes. In cancer progression, miRNAs act as oncogenes or tumor suppressors to regulate gene expression. As a result of their stability in bodily fluids such as blood, urine, and saliva, they are ideal for non-invasive diagnostic procedures. Machine learning (ML) models can identify discriminative miRNAs for various cancers, such as breast, lung, colorectal, and kidney cancers. The integration of ML with miRNA data has demonstrated significant potential for differentiating cancerous tissues from normal tissues and identifying clinically relevant biomarkers. For instance, techniques such as feature engineering and selection, including recursive ensemble selection and miRNA-mRNA network analysis, have been shown to enhance both model accuracy and interpretability. Methods based on Random Forest (RF) and Support Vector Machines (SVM) have successfully classified breast cancer subtypes, and miRNA signatures from fecal samples have been highly effective in diagnosing colorectal cancer. Furthermore, deep learning and neuro-fuzzy systems support kidney cancer analysis, highlighting miRNA-driven ML's role in cancer diagnostics and personalized treatment. This review illustrates the transformative potential of miRNA-driven ML models for advancing cancer diagnostics and enabling personalized treatment strategies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102506"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crucial involvement of transforming growth factor beta (TGF-β)/Smad signaling regulation by miR-204-5p in cataract and posterior capsular opacification","authors":"Javad Sadeghi ,&nbsp;Somayeh Ghavidel Yazdi ,&nbsp;Kimia Arabi ,&nbsp;Meysam Moghbeli ,&nbsp;Vahid Hajali ,&nbsp;Fatemeh Forouzanfar ,&nbsp;Ehsan Saburi","doi":"10.1016/j.bbrep.2026.102522","DOIUrl":"10.1016/j.bbrep.2026.102522","url":null,"abstract":"<div><div>Worldwide, cataracts remain the leading cause of irreversible blindness, primarily driven by age-related changes and free radical-mediated lens damage. Posterior capsular opacification (PCO) is a common complication following cataract surgery, arising from aberrant proliferation and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs). The transforming growth factor-β (TGF-β)/Smad signaling cascade is among the most critical pathways underlying both cataractogenesis and PCO, as it drives EMT and subsequent fibrotic alterations. MicroRNAs have emerged as key regulators of ocular homeostasis, with miR-204-5p being particularly relevant. Highly expressed in the lens, miR-204-5p has been shown to target TGFBR2, a core component of the TGF-β/Smad pathway, and thereby suppress downstream signaling. Downregulation of miR-204-5p appears to enhance TGF-β signaling, which may contribute to lens fibrosis and opacification during cataract development or after surgery. This article reviews current understanding of the interplay between miR-204-5p and the TGF-β/Smad signaling pathway in LECs, focusing on their roles in EMT and fibrotic progression. We also highlight experimental evidence supporting miR-204-5p as a promising candidate for PCO prevention. Emerging evidence also suggests that miR-204-5p regulates oxidative stress and mitochondrial homeostasis through additional targets in lens epithelial cells, highlighting its broader therapeutic potential. Elucidating crosstalk between signaling and epigenetic regulation in LEC biology opens new avenues for non-surgical management of cataracts and PCO. This review underscores the need for further research into miRNA-mediated modulation of fibrotic signaling, establishing this as an innovative and promising direction in molecular ophthalmic therapy.</div></div><div><h3>Clinical trial number</h3><div>not applicable.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102522"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chidamide and Anlotinib act synergistically in Jurkat cells by inhibiting the Hippo signaling pathway","authors":"Tao Ma ,&nbsp;Yuan Yu ,&nbsp;Shuting Yang ,&nbsp;Qiong Xiao ,&nbsp;Xiuqin Zuo ,&nbsp;Gang Wei ,&nbsp;Yan Chen","doi":"10.1016/j.bbrep.2026.102469","DOIUrl":"10.1016/j.bbrep.2026.102469","url":null,"abstract":"<div><h3>Background</h3><div>T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive hematologic malignancy characterized by drug resistance, relapse and poor prognosis. Chidamide, a histone deacetylase inhibitor, has shown epigenetic therapeutic potential in T-ALL, but its efficacy is limited and acquired drug resistance exists. To overcome these limitations, we systematically evaluated the synergistic Combination effects of three drug candidates, OTX-015 (BET inhibitor), Metformin (metabolic regulator), and Anlotinib (multitargeted tyrosine kinase inhibitor), with Chidamide.</div></div><div><h3>Methods</h3><div>We chose Jurkat cells, a cell line for T-ALL, for our experiments. With the CCK-8 trial, we chose the most efficacious Combination of Anlotinib and Chidamide, for the follow-up trial. The antitumor activity of Chidamide and Anlotinib alone or in Combination on Jurkat cells was detected by cell proliferation, apoptosis and cell cycle assay. Transcriptome sequencing and Western blotting were used to identify the key signaling pathways.</div></div><div><h3>Results</h3><div>Jurkat cells treated with Anlotinib showed significant inhibition of cell viability, G2/M arrest and apoptosis. Combination therapy with Chidamide synergistically potentiates these effects. Mechanistically, the Combination treatment inhibited the components of the Hippo pathway (<em>CCN2</em> and <em>YAP</em>), suppressed the PI3K-Akt signaling pathway, and remodeled the expression of extracellular matrix (ECM) -related genes. Transcriptomic analysis further highlighted the enrichment of ECM organization and PI3K-Akt pathway.</div></div><div><h3>Conclusions</h3><div>Chidamide and Anlotinib synergistically inhibit Hippo signaling pathway, which reveals a novel “dual epigenetic kinase targeting” strategy for the treatment of T-ALL. Future studies should validate these findings in vivo and investigate the impact of the metabolic microenvironment on therapeutic efficacy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102469"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A workflow for quantifying cell quiescence in 3D spheroids","authors":"Maria Rita Assenza ,&nbsp;Federica Barbagallo ,&nbsp;Fabiola Moretti","doi":"10.1016/j.bbrep.2026.102467","DOIUrl":"10.1016/j.bbrep.2026.102467","url":null,"abstract":"<div><div>Quiescence is a reversible, tightly regulated state in which cells exit the cell cycle while retaining the potential to re-enter proliferation upon an appropriate stimulus. In solid tumors, quiescent cancer cells are thought to contribute to therapy resistance and disease relapse, especially in poorly vascularized regions. Detecting these dormant cells could be key to predicting therapeutic outcomes and personalizing treatment. To assess the metabolic state of individual cells, we developed a fluorescence-based method using acridine orange (AO) staining, paired with algorithm-driven quantification. By measuring AO-RNA and AO-DNA signals, we distinguished metabolic differences in 3D non-small cell lung cancer spheroids. The RNA/DNA staining ratio correlated with transcriptional activity, validating this approach as a reliable readout of cell state. This method provides a powerful tool to uncover hidden pockets of drug-resistant, quiescent cancer cells in 3D culture.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102467"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterial activity of peptide derivatives of dermaseptins against multidrug-resistant Klebsiella pneumoniae and Staphylococcus epidermis","authors":"Houda Haddad ,&nbsp;Reyadh R. AL-Rashidi ,&nbsp;Ahmed Loghmari ,&nbsp;Wissal Sahtout ,&nbsp;Raja Boukadida ,&nbsp;Rihem Dahmene ,&nbsp;Emeny Ettouil ,&nbsp;Houcemeddine Othman ,&nbsp;Ines Ouahchi ,&nbsp;Amira Zaϊri","doi":"10.1016/j.bbrep.2026.102449","DOIUrl":"10.1016/j.bbrep.2026.102449","url":null,"abstract":"<div><div>The emergence of infections caused by multi-drug resistant bacteria (MDR) to antibiotic treatments poses a significant challenge in the healthcare field. Indeed, the resistance of MDR such as: <em>Klebsiella pneumonia</em> and <em>Staphyloccus epidermidis</em> to antibiotics has become an increasingly concerning issue, especially in hospital settings, necessitating the development of new therapies and more potent antimicrobial agents. Although numerous conventional antibiotic agents have been developed in recent years, but many of them still present toxicity to eukaryotic cells, despite their significant efficacy against multi-resistant microorganisms. Therefore, antimicrobial peptides (AMPs), particularly, dermaseptins (DRSs), are considered promising candidates against MDR, mainly due to their low toxicity and their different mode of action compared to conventional antibiotics. Indeed, these peptides are generally less likely to lead to the resistance phenomena observed for traditional antibiotics. The objectives of this study were to examine the physicochemical and structural properties of peptide derivatives of dermaseptin S4 and B2, and to ascertain their antibacterial potency against <em>Staphylococcus epidermis</em> and <em>Klebsiella pneumoniae.</em> The dermaseptin peptide derivatives used in this study were K₄K₂₀S4, K₄S4(1–16), B2 and K₃K₄B2. In this research, we describe the synthesis and the bioactivity of DRSs and their derivatives against <em>Staphylococcus epidermis</em> and <em>Klebsiella pneumoniae</em>. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. The cytotoxicity of DRSs was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 6.25 to 25 μg/ml and Minimum Bactericidal Concentrations (MBCs) ranging from 12.5 to 50 μg/ml. In summary, these findings indicate that dermaseptins could serve as promising lead compounds for the development of potent antibacterial agents targeting infections caused by <em>Klebsiella pneumoniae</em> and <em>Staphylococcus epidermidis</em>.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102449"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative spatial whole transcriptome analysis of matched frozen and formalin-fixed paraffin-embedded colorectal cancer tissues","authors":"Kullanist Thanormjit ,&nbsp;Thanawat Suwatthanarak ,&nbsp;Tantip Arigul ,&nbsp;Amphun Chaiboonchoe ,&nbsp;Onchira Acharayothin ,&nbsp;Piroon Jenjaroenpun ,&nbsp;Vitoon Chinswangwatanakul ,&nbsp;Pariyada Tanjak","doi":"10.1016/j.bbrep.2025.102413","DOIUrl":"10.1016/j.bbrep.2025.102413","url":null,"abstract":"<div><div>Spatial transcriptomic technology enables resolving a tumor microenvironment heterogeneity of colorectal cancer (CRC) tissue samples. However, there is limited evidence regarding the relative strengths and weaknesses of different CRC sample types and preservation methods, including formalin-fixed paraffin-embedded (FFPE), fresh frozen (FF) and snap frozen (SF). Here, we examine gene expression profiles in 36 tissue areas, FFPE, FF and SF samples, derived from a patient with stage IV CRC, using spatial analysis of the whole transcriptome. The tissue samples obtained from surgical resection of the cancer were subjected to a detailed histological evaluation and spatial transcriptomics analysis to compare the quality of the sample between different preservation methods. Spatial transcriptomic analysis demonstrated that FFPE tissue samples offered improved resolution of cellular morphology in the tumor microenvironment, facilitating greater detail of gene expression and cell types. In contrast, gene expression analysis of FF and SF tissues embedded in optimal cutting temperature compound revealed a high level of CRC gene expression. FFPE, FF and SF samples shared a significant overlap among the top 300 genes that were strongly associated with key biological processes in CRC. In summary, the spatial analysis of the whole transcriptome across FFPE, FF and SF CRC tissues revealed intratumoral heterogeneity and highlighted key transcriptomic signatures, suggesting the specific value of different tissue preservation methods in the profiling of CRC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102413"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating psychological stress-induced cardiac injury: The impact of CB2R agonists on endoplasmic reticulum stress and mitophagy","authors":"Chenke Ma ,&nbsp;Wenbin Gai ,&nbsp;Kan Zhang ,&nbsp;Cheng Qin","doi":"10.1016/j.bbrep.2025.102425","DOIUrl":"10.1016/j.bbrep.2025.102425","url":null,"abstract":"<div><h3>Background</h3><div>Psychological stress is a recognized contributor to cardiac injury and disease; however, the molecular mechanisms underlying this relationship remain incompletely understood, and effective therapeutic strategies are still limited.</div></div><div><h3>Materials and methods</h3><div>DEGs were identified from our sequencing data and GEO datasets, intersected with ER stress/mitophagy-related genes, and then prioritized by machine-learning and network analyses; pathway activity, immune signatures, molecular subtypes, and miRNA–mRNA interactions (DIANA-TarBase) were further characterized and experimentally validated.</div></div><div><h3>Results</h3><div>In cardiac injury induced by psychological stress, 38 differentially expressed ER stress- and mitophagy-related genes were identified. Through methods such as LASSO regression, four key genes—Foxo3, Pparg, Sirt1, and Stat3—were selected. ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720). Correlation analysis revealed that Sirt1 exhibited significant positive correlations with CD56bright natural killer cells, MDSCs, and Type 1 T helper cells. Pparg showed a notable positive association with Type 1 T helper cells, while γδ T cells showed significant negative correlations with Stat3, Sirt1, Pparg, anRd Foxo3. Treatment with a cannabinoid type 2 receptor (CB2R) agonist notably downregulated the expression of these four key genes.</div></div><div><h3>Conclusion</h3><div>This study provides mechanistic insight into molecular processes underlying psychological stress–induced cardiac injury. The identified four-gene module may serve as an exploratory molecular signature and a starting point for evaluating CB2R agonism as a modulator of ER stress and mitophagy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102425"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}