Experimental Biology And Medicine (Maywood, N.J.)[JOURNAL]
Sun
200 papers
The causal relationship between obstructive sleep apnea and otitis media: a bidirectional Mendelian randomization study.
Guo R, Zhang Y, Chen Y … +9 more , Sha W, Kou W, Xu C, Lei Y, Zhang N, Yang L, Guo Y, Zhang H, Wang Z
Exp Biol Med (Maywood) · 2025 · PMID 41323251 · Full text
Obstructive sleep apnea (OSA) is manifested as periodic collapse of the upper airway during sleep. Otitis media is a spectrum of infectious and inflammatory diseases involving the middle ear. In this study, we sought to...
Obstructive sleep apnea (OSA) is manifested as periodic collapse of the upper airway during sleep. Otitis media is a spectrum of infectious and inflammatory diseases involving the middle ear. In this study, we sought to determine the causal effect of OSA on otitis media using a bidirectional, two-sample Mendelian randomization (MR) analysis. We analyzed the data from two different, extensive genome-wide association studies (GWAS) and selected OSA-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Bidirectional MR analysis was conducted using the inverse-variance weighted (IVW) method. To ensure the robustness of the results, alternative sensitivity analysis procedures were performed, including MR-Egger, the MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. In the forward MR analysis, OSA was correlated with an increased risk of acute suppurative otitis media (odds ratio, 1.164; 95% confidence interval, 1.056-1.283; = 0.002) and suppurative and unspecified otitis media (odds ratio, 1.150; 95% confidence interval, 1.059-1.249; 0.001). All reverse MR analyses showed that otitis media had no causal effect on OSA ( > 0.05). The MR analysis supports that OSA contributes to the development of otitis media. Thus, managing OSA may be beneficial in treating otitis media.
Curcumin-enhanced elvitegravir therapy mitigates neuroinflammation and cognitive deficits in EcoHIV mice.
Godse S, Zhou L, Sinha N … +3 more , Salman M, Ishrat T, Kumar S
Exp Biol Med (Maywood) · 2025 · PMID 41281680 · Full text
HIV-associated neurocognitive disorders (HAND) persist in up to 50% of people living with HIV (PLWH) despite effective antiretroviral therapy (ART), driven by chronic neuroinflammation, oxidative stress, and neuronal dam...
HIV-associated neurocognitive disorders (HAND) persist in up to 50% of people living with HIV (PLWH) despite effective antiretroviral therapy (ART), driven by chronic neuroinflammation, oxidative stress, and neuronal damage. This study investigates the therapeutic potential of combining elvitegravir (EVG), an integrase strand transfer inhibitor, with curcumin (CUR), a natural polyphenol with anti-inflammatory and antioxidant properties, in a murine EcoHIV model of HAND. EcoHIV-infected mice were treated with EVG, CUR, or their combination (EVG + CUR), and cognitive, motor, and molecular outcomes were evaluated. Behavioral assays revealed that EcoHIV infection significantly impaired non-spatial working memory, spatial learning, and motor performance, as assessed by the Novel Object Recognition (NOR)and Morris water Maize (MWM) tests and CatWalk gait analysis. While EVG or CUR alone showed modest improvements, the EVG + CUR combination significantly restored cognitive function, reduced escape latencies in the MWM, and improved motor performance, including gait stability and interlimb coordination. At the molecular level, EVG + CUR treatment attenuated neuroinflammation by reducing pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and chemokine (MCP-1) in the brain and plasma, particularly following intranasal administration. Additionally, EVG + CUR significantly reduced oxidative DNA damage and preserved neuronal integrity without disrupting CNS homeostasis. These findings demonstrate that the EVG + CUR combination effectively targets both viral persistence and the underlying neuroinflammatory and oxidative mechanisms driving HAND. By improving cognitive and motor function while mitigating neuroinflammation and oxidative stress, EVG + CUR represents a promising adjunctive therapy for HAND, offering a multifaceted approach to addressing the complex pathophysiology of HIV-associated neurocognitive disorders.
Bioinformatics-based screening and validation of ferroptosis-related genes in sepsis and type 2 diabetes mellitus.
Xiao H, Ding Z, Liu C … +2 more , He X, Tao Y
Exp Biol Med (Maywood) · 2025 · PMID 41194984 · Full text
Emerging clinical evidence underscores a bidirectional epidemiological linkage between sepsis and type 2 diabetes mellitus (T2DM). This study mechanistically investigates the underlying pathogenesis of this comorbidity,...
Emerging clinical evidence underscores a bidirectional epidemiological linkage between sepsis and type 2 diabetes mellitus (T2DM). This study mechanistically investigates the underlying pathogenesis of this comorbidity, specifically focusing on the role of ferroptosis-related genes in its pathogenesis. A total of 1204 shared genes between sepsis and T2DM were screened using datasets from sepsis (GSE65682) and T2DM (GSE76894). GO and KEGG enrichment analyses, combined with WGCNA, were performed to identify key pathways and hub genes. Three signaling pathways-MAPK, adherens junction, and peroxisome-were significantly associated with the sepsis-T2DM interaction. Subsequent Pearson correlation analysis implicated ferroptosis as a critically involved process. Five core ferroptosis-related genes, including CDC25B, DPP7, FBXO31, PTCD3, and CNPY2, were were identified and experimentally validated using qRT-PCR. Furthermore, based on cMAP, we screened eight candidate drugs targeting these genes. Echinacea and Ibudilast were predicted to possess the greatest preclinical potential among them. This study provides a deeper insight into the shared pathogenesis of sepsis and T2DM, highlighting the pivotal role of ferroptosis in the development and progression of this comorbidity. Our findings offer preliminary insights into the sepsis-T2DM comorbidity, highlighting ferroptosis as a potential key pathological mechanism and identifying candidate targets for future therapeutic exploration.
TIMAP downregulation in Burkitt's lymphoma reveals key molecules and signaling pathways in B-cell lymphomagenesis.
Obeidat M, Tadros S, Ismail B … +1 more , Al-Khaldi A
Exp Biol Med (Maywood) · 2025 · PMID 41170526 · Full text
Burkitt's lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a r...
Burkitt's lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a regulatory subunit of protein phosphatase 1 catalytic subunit, enriched in lymphoid tissues, and upregulated in various cancers. Despite suggestions that TIMAP promotes lymphomagenesis in a -driven model, its precise role remains unclear. This study aimed to investigate the contribution of TIMAP to B-cell lymphomagenesis by examining transcriptomic changes upon TIMAP downregulation in BL cells. Raji BL cells were transfected with 2'Fluoro Arabinonucleic acid (FANA)-antisense oligonucleotides (ASO) targeting TIMAP (FANA-ASO-TIMAP) or a scramble control (FANA-ASO-Scramble). TIMAP expression was significantly reduced at the mRNA (0.70 ± 0.04, p = 0.001) and protein levels (median = 0.73, IQR = 0.13, p = 0.002). RNA sequencing identified 2,368 differentially expressed genes (DEGs), of which 1,326 were upregulated, and 1,042 were downregulated. Gene Ontology analysis revealed that the DEGs were primarily involved in cellular processes, DNA replication, intracellular signal transduction, and apoptosis. Pathways related to lymphoma progression, such as B-cell receptor signaling, p53 signaling, and mTOR signaling, were notably affected. Key genes such as , , , and were among the most dysregulated, highlighting TIMAP's role in critical oncogenic pathways in B-cell Lymphoma. These findings suggest that TIMAP is a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis and could serve as a potential therapeutic target for novel treatments.
Glaucoma and cardiovascular disease: a bidirectional two-sample Mendelian randomization analysis.
Jin D, Sun J, Zhang W … +2 more , Zhang M, Li C
Exp Biol Med (Maywood) · 2025 · PMID 41170525 · Full text
Many studies reported that glaucoma is associated with cardiovascular disease (CVD). This study aims to investigate the potential causal relationship between glaucoma and CVD using a bidirectional two-sample Mendelian ra...
Many studies reported that glaucoma is associated with cardiovascular disease (CVD). This study aims to investigate the potential causal relationship between glaucoma and CVD using a bidirectional two-sample Mendelian randomization (MR) analysis. The genome-wide association studies (GWAS) of glaucoma and CVD were downloaded from the IEU OpenGWAS project. The CVD included unstable angina pectoris (UAP), coronary artery disease (CAD), high blood pressure (HBP), myocardial infarct (MI), heart failure (HF), ischemic stroke (IS), atrial fibrillation (AF), and pulmonary embolism (PE). The inverse variance weighting (IVW) analysis was the primary method in MR analysis. Meanwhile, sensitivity analysis and statistical power tests were performed. The random effects IVW method showed a causal relationship between glaucoma and a decreased risk of MI (Odds ratio (OR): 0.94, 95% confidence interval (CI): 0.89-0.99; P = 0.012). In the reverse MR analysis, genetic susceptibility of UAP (OR: 1.12, 95% CI: 1.02-1.23; P = 0.022), CAD (OR: 1.1, 95% CI: 1-1.21; P = 0.041), and HBP (OR: 1.83, 95% CI: 1.25-2.67; P = 0.002) was significantly linked to an increased risk of glaucoma. MR-Egger (P = 0.005) and IVW (P = 0.005) methods found that HBP presented different degrees of heterogeneity. The random effects IVW method also demonstrated that HBP is the risk factor for glaucoma (P = 0.0017). Although reverse MR initially suggested a potential association between CAD and glaucoma, MVMR showed no causal relationship after adjusting for obesity and BMI. The MR analysis found that glaucoma serves as a protective factor for MI, while UAP and HBP were risk factors for glaucoma in the European population, which may contribute to preventing and managing glaucoma and CVD.
Deciphering the microbiological mechanism of Tongxie Yaofang in treating IBS-D: a multimodal mechanistic study in mice integrating network pharmacology, computational simulation, and 16S rRNA sequencing.
Yu D, Tian Q, Shen J … +3 more , Fang L, Tan Z, Cai Y
Exp Biol Med (Maywood) · 2025 · PMID 41114050 · Full text
Irritable bowel syndrome with diarrhea (IBS-D), associated with the traditional Chinese medicine (TCM) pattern of liver hyperactivity with spleen deficiency pattern, lacks effective Western treatments. The modern biologi...
Irritable bowel syndrome with diarrhea (IBS-D), associated with the traditional Chinese medicine (TCM) pattern of liver hyperactivity with spleen deficiency pattern, lacks effective Western treatments. The modern biological relevance of the "intestine-liver-bile acid" axis aligns with this TCM concept, and interactions between intestinal microbiota and diarrhea remain unclear. Network pharmacology, molecular docking, and molecular dynamics were applied to elucidate the mechanisms and compound-target stability of Tongxie Yaofang. An IBS-D mouse model was established using Mill. combined with confinement stress. Histopathological changes in the liver and spleen were assessed by hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA) was performed to quantify total bile acid levels in serum and liver. Ultimately, 16S rRNA high-throughput sequencing was employed to identify predominant and distinctive bacterial species. Network pharmacology and molecular docking revealed that Tongxie Yaofang acts primarily through the TNF-α and IL-17 pathways. Molecular dynamics confirmed strong binding affinities between active compounds (naringenin, divaricatol, and kaempferol) and target proteins. , Tongxie Yaofang alleviated colonic inflammation, increased serum bile acid levels, reduced hepatic bile acid concentrations, and increased intestinal microbial diversity and abundance. The therapeutic effects of Tongxie Yaofang on IBS-D are mechanistically linked to its multi-target actions, including suppression of inflammatory responses, inhibition of pathogenic bacterial overgrowth, restoration of immune homeostasis, and modulation of intestinal microbiota composition toward a probiotic-enriched community.
High-fidelity, personalized cardiac modeling via AI-driven 3D reconstruction and embedded silicone rubber printing.
Wang X, Li Y, Liang Z … +2 more , Du R, Song T
Exp Biol Med (Maywood) · 2025 · PMID 41103456 · Full text
The burgeoning clinical demand for patient-specific cardiac modeling encounters significant challenges. The current clinical cardiac models are either difficult to manufacture or lack of detailed geometric structures and...
The burgeoning clinical demand for patient-specific cardiac modeling encounters significant challenges. The current clinical cardiac models are either difficult to manufacture or lack of detailed geometric structures and hence, often fail to incorporate important patient-specific characteristics. Moreover, most 3D-printable soft materials, such as Thermoplastic Poly-Urethane (TPU) or elastic resins, exhibit insufficient flexibility and biocompatibility to accurately mimic cardiac tissues, therefore limiting their ability to truly replicate patient-specific cardiac conditions. To address these limitations, we propose an innovative method for patient-specific cardiac substructure reconstruction based on the integration of Artificial Intelligence (AI) and embedded 3D printing. First, by combining medical imaging data (CT scan) with AI-driven high-precision 3D reconstruction algorithms, the new method segments the patient-specific cardiac structure into 10 substructures. The average Dice coefficient across the ten substructures is 0.87. Second, it uses an embedded 3D printing technique which utilizes silicone rubber matrix as supporting structure and uses diluted catalyst ink to extrude onto the supporting matrix. Through precise regulation of the matrix composition, material deposition rate and curing time, it can fabricate high-fidelity, complex 3D patient-specific silicone heart models with the average dimensional error less than 0.5 mm. The proposed method can substantially reduce manual intervention and post-processing time. The fabricated models provide valuable morphological insights for cardiovascular diagnosis and treatment planning. It is believed that many clinic applications will follow.
Unveiling the dual role of CD3G: a diagnostic biomarker for depression and its oncogenic implications.
Gao H, Wu T, Xue J … +3 more , Liu J, Wen D, Huang G
Exp Biol Med (Maywood) · 2025 · PMID 41103455 · Full text
Depression has been increasingly associated with immune system dysregulation. This study investigates the potential of CD3 Gamma Subunit of T-Cell Receptor Complex (CD3G) as a diagnostic marker for depression, while also...
Depression has been increasingly associated with immune system dysregulation. This study investigates the potential of CD3 Gamma Subunit of T-Cell Receptor Complex (CD3G) as a diagnostic marker for depression, while also examining its role across various cancer types. Comparative analyses of immune cell infiltration and pathway activities were conducted using single-sample Gene Set Enrichment Analysis (ssGSEA) on datasets GSE98793. Depression patients were defined based on clinical diagnoses and compared to healthy controls (HC) without any psychiatric disorders. Differentially expressed genes (DEGs) were identified, followed by weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) and logistic regression to pinpoint independent diagnostic markers. Functional enrichment analyses were performed to explore the biological implications of CD3G expression in depression. Pan-cancer analyses were also conducted to investigate CD3G's role in cancer. Depression patients exhibited significant decreases in CD8 T cells, cytotoxic cells, T cells, T helper cells, Tgd, and Th2 cells, with increased levels of dendritic cells and neutrophils compared to HC. Immune pathway activities showed increased antimicrobial, chemokine, cytokine, and TNF family member activities, with decreased TCR signaling activity in depression patients. CD3G was identified as a key immune-related gene and independent diagnostic marker for depression, validated by GSE76826 dataset. Low CD3G expression in depression was associated with enhanced immune response and inflammatory pathways. In pan-cancer analysis, CD3G was upregulated in numerous cancers and correlated with immune cell infiltration and oncogenic pathways. The study highlights significant dysregulation in immune cell infiltration and pathway activities in depression, with CD3G emerging as a critical immune-related gene and potential diagnostic marker. CD3G's role in immune modulation and cancer underscores its relevance in both depression and oncology, suggesting potential therapeutic targets and prognostic indicators.
Therapeutic effects of mesenchymal stromal cell secretome in liver fibrosis with acute lung injury.
Martins ACRN, Silva KR, Pereira ACS … +6 more , Paris GC, Nascimento ALR, Aiceles V, Cortez EAC, Thole AA, de Carvalho SN
Exp Biol Med (Maywood) · 2025 · PMID 41098324 · Full text
Chronic liver disease (CLD) is a widespread condition and liver fibrosis is a common hallmark. The COVID-19 pandemic has drawn awareness over emerging pathogens that pose severe risks for chronic disease patients, whose...
Chronic liver disease (CLD) is a widespread condition and liver fibrosis is a common hallmark. The COVID-19 pandemic has drawn awareness over emerging pathogens that pose severe risks for chronic disease patients, whose management is complicated because most drugs can overload liver metabolism, therefore therapeutic alternatives are needed. Aims: based on the difficulty of treating CLD patients during respiratory infections, this study focused on the therapeutic evaluation of adipose-derived mesenchymal stromal cell (ASC) secretome. Methods: the effects of ASC secretome were evaluated in a preclinical murine model of liver fibrosis induced by thioacetamide (TAA) and acute lung injury induced by lipopolysaccharide, using histological and cytokine profile analyses. ASC secretome exhibited therapeutic effects alleviating fibrogenesis and inflammation, decreasing plasmatic inflammatory markers (cytokines IL-6, IL-17A and TNF-α), and restoring immune homeostasis. The secretome reduced liver collagen accumulation and IL-6 levels and restored lung cytoarchitecture, decreasing levels of CD68 and TNF-α. These results provide a preclinical basis for potential clinical use of the ASC secretome and its products, advancing the concept of cell-free, systemically active interventions for complex tissue injuries, and reinforcing the potential of its paracrine factors to modify pathological responses and promote tissue regeneration in combined chronic-acute diseases.
Multi-omics analysis identifies the unique high-FDCSP basal cells in triple-negative breast cancer.
Lu X, Chen Z, Shao Y
Exp Biol Med (Maywood) · 2025 · PMID 41081066 · Full text
Follicular dendritic cell secreted protein (FDCSP) is highly expressed in various cancers and has been implicated in tumor migration and invasion, yet its role in triple-negative breast cancer (TNBC) remains poorly under...
Follicular dendritic cell secreted protein (FDCSP) is highly expressed in various cancers and has been implicated in tumor migration and invasion, yet its role in triple-negative breast cancer (TNBC) remains poorly understood. Our findings revealed that FDCSP expression was significantly elevated in TNBC compared to normal breast tissue, whereas its expression was significantly reduced in non-TNBC. In TNBC, high FDCSP expression was associated with an increased mutation rate of TP53 and influenced the infiltration of B cells and macrophages. Single-cell transcriptome analysis demonstrated that FDCSP was predominantly highly expressed in basal cells but exhibited low expression in luminal epithelial cells. This observation was further corroborated by spatial transcriptome (ST) analysis. Immunohistochemistry (IHC) assay also confirmed the distinct expression patterns of FDCSP. Cell-cell interaction and receptor-ligand pair analyses indicated that macrophages could interact with the receptor epidermal growth factor receptor (EGFR) in FDCSP highly expressed basal cells by secreting transforming growth factor-β1 (TGF-β1). Then, the co-localization of FDCSP and EGFR in TNBC basal cells was verified by IHC and immunofluorescence (IF) assay. Additionally, we discovered that FDCSP possesses strong predictive capabilities for distinguishing between responders and non-responders to Immune checkpoint blockade (ICB) treatment. Finally, leveraging the CARE database, we identified 14 potential FDCSP-related target drugs. These findings highlight the unique expression pattern of FDCSP in breast cancer, revealing FDCSP as a promising target for therapeutic strategies in TNBC.
Platelet-rich plasma in peripheral nerve injury repair: a comprehensive review of mechanisms, clinical applications, and therapeutic potential.
Shang K, Liu Y, Qadeer A
Exp Biol Med (Maywood) · 2025 · PMID 41063785 · Full text
Peripheral nerve injuries (PNIs) pose a significant clinical challenge, often leading to incomplete functional recovery despite current treatments. Platelet-rich plasma (PRP), which contains high levels of growth factors...
Peripheral nerve injuries (PNIs) pose a significant clinical challenge, often leading to incomplete functional recovery despite current treatments. Platelet-rich plasma (PRP), which contains high levels of growth factors and bioactive molecules, has emerged as a promising regenerative therapy for nerve repair and restoring function. This review consolidates current evidence on PRP applications in treating peripheral nerve injuries, examining molecular mechanisms, clinical outcomes, and therapeutic potential. PRP markedly enhances nerve regeneration, improves recovery of sensory and motor functions, and alleviates neuropathic pain across various nerve injuries. It promotes axonal growth, reduces scar formation, stimulates Schwann cell proliferation, and modulates inflammation through the release of neurotrophic factors, including PDGF, VEGF, TGF-β, and IGF-1. Combining PRP with surgical techniques and biomaterial scaffolds yields better therapeutic results. Key factors influencing efficacy include platelet concentration, leukocyte content, activation methods, and patient-specific variables. PRP is a safe and effective option for peripheral nerve injury repair. However, challenges persist in standardizing preparation protocols, optimizing treatment timing, and fully understanding molecular mechanisms. Future research should focus on personalized PRP formulations, combination therapies, and large-scale randomized controlled trials to develop definitive clinical guidelines.
Variational autoencoder enhanced analysis of energy metabolism and autophagy in exercising cardiomyocytes.
Chen L, Yang Y
Exp Biol Med (Maywood) · 2025 · PMID 41059273 · Full text
Autophagy of myocardial cells involves the interaction of multiple molecular signaling pathways, and regulatory factors, while existing methods are difficult to handle. This study utilized the variational autoencoder (VA...
Autophagy of myocardial cells involves the interaction of multiple molecular signaling pathways, and regulatory factors, while existing methods are difficult to handle. This study utilized the variational autoencoder (VAE) model to reveal the characteristic distribution of myocardial cell energy autophagy under different exercise conditions. First, this paper is based on mass spectrometry analysis, enzyme-linked immunosorbent assay ELISA (Enzyme-Linked Immunosorbent Assay) to determine the cardiomyocyte metabolite concentration data, and RNA-Seq (Ribonucleic Acid-Sequencing) to collect genes related to cardiomyocyte energy metabolism and autophagy expression data; in the VAE model, this paper utilizes the full connectivity layer to encode the data into potential representations, and reconstructs the numerical data through the numerical data decoder. The loss function is defined as the data reconstruction error and KL (Kullback-Leibler) scatter, and Adam is used to optimize the training process; the features are analyzed and the classification performance is verified under different motion conditions based on RF (Random Forest); the relationship between the features and metabolite concentration and gene expression is analyzed by LASSO (Least Absolute Shrinkage and Selection Operator) regression model to analyze the relationship between features and metabolite concentration and gene expression; the features in the latent space are downscaled using t-SNE (t-distributed Stochastic Neighbor Embedding) to visualize the feature distribution; finally, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-Cas9) knockdown experiments to reveal the importance of AMPK, PGC1A, CPT1B, and SIRT1 in cardiomyocyte autophagy and energy metabolism, which provide potential targets for future gene-based therapies.
A case study of long-term disease burden in a rural community near an open burn facility.
Bakshi A, Baconguis L, Al-Mamun MA … +3 more , Yu Q, Richmond-Bryant J, Cormier SA
Exp Biol Med (Maywood) · 2025 · PMID 41049607 · Full text
Open burning and open detonation (OB/OD) of explosive and hazardous wastes creates various toxic waste products, including particulate matter, that is released into the atmosphere and capable of generating significant he...
Open burning and open detonation (OB/OD) of explosive and hazardous wastes creates various toxic waste products, including particulate matter, that is released into the atmosphere and capable of generating significant health impacts upon exposure. The last commercially run OB/OD thermal treatment facility in operation in the United States is located near the rural community of Colfax in central Louisiana. To evaluate the community's concerns about the potential health impacts from air pollution due to the facility's regular open burning of explosive and hazardous wastes, we examined the disease burden in Colfax compared to the surrounding parish and state. In a cross-sectional study, we analyzed hospitalizations and mortality (2000-2018) where a primary or secondary disease code was associated with cardiovascular, respiratory, thyroid and skin disease. After adjusting for age, sex and race, morbidity and mortality due to cardiovascular and respiratory diseases were significantly higher in Colfax compared to the surrounding areas. In addition, comparing age-adjusted rates across geographies, stratified by race and sex, revealed place-based differences within sub-populations. The higher estimated prevalence of disease conditions is consistent with long-term particulate matter exposure and suggests a need for comprehensive exposure studies within the community. Our data further stress the need for enhanced epidemiological studies and tailored statistical methods to address exposures and environmental health impacts in rural populations, with fewer than 2,500 individuals, like Colfax.
Prognostic significance and therapeutic implications of redox metabolism-related genes in head and neck squamous cell carcinoma.
Yang L, Hai J, Liu J … +3 more , Shen S, Su L, Sun J
Exp Biol Med (Maywood) · 2025 · PMID 41049606 · Full text
Head and neck squamous cell carcinomas (HNSC) are associated with alterations in redox metabolism. This study aims to identify differentially expressed genes (DEGs) related to redox metabolism in HNSC and assess their pr...
Head and neck squamous cell carcinomas (HNSC) are associated with alterations in redox metabolism. This study aims to identify differentially expressed genes (DEGs) related to redox metabolism in HNSC and assess their prognostic values. We utilized the limma package for identifying redox metabolism-related DEGs and performed univariate and multivariate Cox regression analyses to evaluate their prognostic significance. Gene set variation analysis (GSVA), immune cell infiltration analysis, and single-cell RNA sequencing were utilized to explore the relationships between gene expression and tumor processes. Chemotherapy sensitivity was assessed based on expression levels. Additionally, pan-cancer analysis was conducted to evaluate expression and its prognostic value across different cancer types. The analysis identified several DEGs with significant prognostic value, including , which was significantly associated with poor prognosis in HNSC patients. High expression correlated with reduced overall survival, disease-specific survival, and progression-free interval. was notably overexpressed in tumor tissues and associated with key oncogenic pathways and immune cell infiltration patterns. Chemotherapeutic drug sensitivity analysis revealed that high expression increased sensitivity to Paclitaxel, Vinblastine, and Sorafenib but decreased sensitivity to Rapamycin. Pan-cancer analysis indicated that is differentially expressed and prognostic across multiple cancer types. Our findings highlight the crucial role of redox metabolism-related DEGs, particularly , in HNSC progression and prognosis. serves as a potential biomarker for prognosis and therapeutic response, warranting further research into its biological functions and potential as a therapeutic target.
Unraveling the pharmacological and therapeutic potential of Ranolazine beyond antianginal drug use: a new insight.
Singh D, Oladimeji-Salami JA, Akindele AJ
Exp Biol Med (Maywood) · 2025 · PMID 40969450 · Full text
Ranolazine (RAN) is an acetanilide and piperazine derivative that selectively blocks the late sodium current in cardiac cells and is prescribed in adults as an add-on medication for the symptomatic management of patients...
Ranolazine (RAN) is an acetanilide and piperazine derivative that selectively blocks the late sodium current in cardiac cells and is prescribed in adults as an add-on medication for the symptomatic management of patients with stable angina pectoris who are insufficiently managed or intolerant of first-line antianginal treatments. RAN was first approved by the U.S. Food and Drug Administration (FDA) in 2006 and the European Medicine Agency in 2008 for the treatment of chronic stable angina. RAN has no substantial effect on hemodynamic indicators, including heart rate and blood pressure. RAN also slows fatty acid oxidation, which increases glucose oxidation, lowers lactic acid generation, and optimizes heart performance. Besides its antianginal effect, RAN has recently revealed additional pharmacological properties such as neuroprotective, hepatoprotective, renal protective, cardioprotective, and antidiabetic effects and other beneficial pharmacological activities. We choose to write this current review paper to address the many hidden pharmacological and therapeutic potentials of RAN beyond its antianginal activity.
An approach to evaluate the effect of inflammatory microvesicles on Ca handling in human-induced pluripotent stem cell-derived cardiomyocytes.
Fischer D, Sha'sha'a M, Schenz J … +9 more , Tayan A, Mertens C, Decker SO, Gallenstein N, Dietrich M, Lajqi T, Hafner A, Weigand MA, Ullrich ND
Exp Biol Med (Maywood) · 2025 · PMID 40950553 · Full text
Microvesicles (MV) isolated from septic individuals were observed to impact systemic hemodynamics and cardiac function. The aim of this study was to analyze the effects of TNFα-induced endothelial MV (TMV) and MV from s...
Microvesicles (MV) isolated from septic individuals were observed to impact systemic hemodynamics and cardiac function. The aim of this study was to analyze the effects of TNFα-induced endothelial MV (TMV) and MV from septic patients (SMV) on beating frequency and Ca transient kinetics of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). MV were isolated from supernatants of TNFα-stimulated primary human pulmonary microvascular endothelial cells (HPMEC) and plasma from 20 sepsis patients by ultracentrifugation and quantified using flow cytometry. Spontaneous Ca transients were measured in hiPSC-CM using the Ca-sensitive ratiometric indicator fura-2 at different time points of incubation with different MV concentrations. At 16 h of incubation, higher MV concentrations showed significant differences, especially regarding decay and beating frequency. Despite high variability, at 10 × 10 MV/mL and 16 h of incubation, TMV significantly decreased frequency compared to control MV (CMV). SMV from septic patients did not reveal any significant effects on Ca transients under these experimental settings. MV isolated from control or TNFα-treated HPMEC affected Ca handling and spontaneous activity of hiPSC-CM, however, the measured effects were not consistent throughout the different conditions. Further refinement of the experiment conditions is needed to specify the exact conditions for crosstalk between endothelium-derived MV and cardiomyocytes.
RNA binding proteins potentially regulate alternative splicing of immune-related genes during the progression of coronary artery disease.
Miao Y, Wang L, Zhao G … +5 more , Gou W, Chen S, Ding C, Li Z, Gao F
Exp Biol Med (Maywood) · 2025 · PMID 40950552 · Full text
RNA-binding proteins (RBPs) are crucial in disease as they regulate the biological functions of RNA. However, their role in coronary artery disease (CAD) progression remains unclear. RNA-seq from peripheral blood of CAD...
RNA-binding proteins (RBPs) are crucial in disease as they regulate the biological functions of RNA. However, their role in coronary artery disease (CAD) progression remains unclear. RNA-seq from peripheral blood of CAD patients and no-CAD controls was analyzed to compare differentially expressed genes (DEGs) and explore their potential functions. The distribution of immune cells was assessed by CIBERSORT algorithm. Alternative splicing (AS) pattern was quantified by SUVA. Immune-related AS events (ASEs) were screened via ImmPort database. Co-expression network of ASEs, differentially expressed RBPs (DERBPs), mitochondrion and apoptosis genes, and immune cells was constructed to clarify their potential functions. A total of 1521 DEGs were detected, including 99 DERBPs, which were mainly downregulated and enriched in mRNA processing, RNA splicing, mRNA transport, and innate immune response pathways in CAD. Seven DERBPs (ANG, C4BPA, DDX60, IFIH1, IPO7, MATR3, OTUD4) were associated with immune function. Analysis of the immune cell fraction demonstrated significant increase in macrophage M0 and CD8 T cells and decrease in resting dendritic cells and activated memory CD4 T cells. Immune-related ASEs correlated with atherosclerotic stenosis were mainly the complex "alt3p/alt5p" splicing types. DERBP-AS's co-expression identified a key A5'SS event of CTSB gene. Co-expression of this event with TST and SYNCRIP may lead to a change in the proportion of macrophage M0 and CD8 T cells, respectively. The mitochondrion and apoptosis genes were also dysregulated in CAD and correlated with four DERBPs. In conclusion, RBPs have potential regulatory role in the progression of CAD by regulating the ASEs of immune-related genes and mediating immune cells composition. These findings highlight RBPs as potential therapeutic targets for CAD.
Integrated analysis of metabolome and microbiome in a mouse model of sodium valproate-induced autism.
Zhao S, Zhang X, Miao Y … +9 more , Gao X, Wan Q, Qiu W, Si H, Han Y, Du X, Feng Y, Liu L, Chen Y
Exp Biol Med (Maywood) · 2025 · PMID 40950551 · Full text
Sodium valproate (SV) has been shown to induce autism in animal models. In this study, the SV method was used to establish a mouse model of autism, and anxiety-like behaviours and learning memory performance were evaluat...
Sodium valproate (SV) has been shown to induce autism in animal models. In this study, the SV method was used to establish a mouse model of autism, and anxiety-like behaviours and learning memory performance were evaluated by behavioural tests. The effects of SV on metabolic profiles and gut microbiota were assessed by integrating gas chromatography-mass spectrometry and 16S ribosomal RNA gene sequencing. Correlations between metabolites and gut microbiota were determined using Spearman correlation coefficient. Behavioral tests, including the three-chambered social assay, repetitive behaviors, open field test, elevated plus-maze test, and novel object recognition test, demonstrated that SV treatment exacerbated anxiety-like behaviors and impeded spatial learning and memory in mice. SV disrupted metabolic pathways in hippocampus, cortex, intestine, and serum, affecting primarily valine, leucine and isoleucine biosynthesis, glycerophospholipid metabolism and glutathione metabolism and so on. SV also altered gut microbiota at the genus level, decreasing the abundances of , , , , and , while increase the abundances of , , and in intestine. The results of correlation analysis showed that in hippocampus, was positively correlated with serine and glycine, while was negatively correlated with them. These findings suggested that SV may contribute to the development of autism progression by altering the gut microbiota abundances and metabolite profiles. This may provide new direction for the management of autism.
Association between systemic immune-inflammation index and 10-year risk of cardiovascular disease in the United States (NHANES 1999-2018).
Yang Y, Tu R, Zhu L … +5 more , Xu G, Yang T, Li Q, Wang C, Yang H
Exp Biol Med (Maywood) · 2025 · PMID 40917490 · Full text
The relationship between the systemic immune-inflammation index (SII) and the risk of developing cardiovascular disease (CVD) over the next 10 years in the United States is largely unknown. The aim of this study is to as...
The relationship between the systemic immune-inflammation index (SII) and the risk of developing cardiovascular disease (CVD) over the next 10 years in the United States is largely unknown. The aim of this study is to assess the association between SII and 10-year CVD risk. This population-based cross-sectional study included 9901 participants aged between 30 and 74 from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The 10-year CVD risk was calculated using the Framingham cardiovascular risk score (FRS). The Pearson test, generalized linear model (GLM) and restricted cubic splines (RCS) were used to analyze the associations between SII and the FRS. Based on the total population, the Pearson test and GLM revealed that there were positive relationships between Ln-transformed SII (Ln (SII)) and the FRS. After adjusting for confounding factors, the odds ratio (OR) for the FRS was 1.52 (95% confidence interval [CI]: 1.12-2.06) per unit increment in Ln (SII) ( = 0.009). Compared to the lowest quartile (Q1) of Ln (SII), the OR for the FRS in the highest quartile (Q4) was 1.89 (95% CI: 1.20-2.98; = 0.007). RCS revealed that there was a linear association between Ln (SII) and the FRS ( for non-linearity = 0.972). As Ln (SII) increased, the value of FRS rose gradually ( for overall trend <0.001). However, the relationship between Ln (SII) and FRS showed ethnic heterogeneity. In conclusion, SII exhibits significant associations with 10-year CVD risk as assessed by the FRS. However, this association varies across ethnic groups, necessitating cautious application and further validation.
Csf1 AD-MSCs promote stroke repair by activating the resident microglia.
Hou J, Zhang S, Luo S … +8 more , Zuo X, Ma F, Wang H, Han P, Zhu P, Wang N, Hou X, Li J
Exp Biol Med (Maywood) · 2025 · PMID 40910104 · Full text
The potential of mesenchymal stromal cells (MSCs) in the treatment of hemorrhagic stroke has been demonstrated; however, their clinical efficacy remains inconsistent and further comprehensive studies on their mechanism o...
The potential of mesenchymal stromal cells (MSCs) in the treatment of hemorrhagic stroke has been demonstrated; however, their clinical efficacy remains inconsistent and further comprehensive studies on their mechanism of action are warranted. In this study, the intracerebral hemorrhage (ICH) rat model was used for intravenous infusion of adipose-derived mesenchymal stromal cells (AD-MSCs) 24 h after modeling. Histopathological techniques and single cell transcriptome sequencing techniques were used to study the mechanism of AD-MSCs promoting the repair of damaged brain tissue. The results indicated that AD-MSCs markedly promote the repair of damaged brain tissues and restored neural function. Single-cell transcriptome sequencing further revealed that this therapeutic effect is specifically through the inhibition of monocyte infiltration in injured brain tissue, promotion of resident microglia proliferation and signaling pathways linked to immune response and neuroprotection. These processes are closely tied to the Csf1 subgroup of AD-MSCs. For acute hemorrhagic stroke, Csf1 AD-MSCs promote the repair of damaged brain tissue by activating resident microglia and inhibiting monocyte infiltration. This study offers novel insights into the mechanisms underlying MSC-based stroke treatment and supports the potential for stable and efficacious MSC therapies.
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