Experimental Biology and Medicine最新文献

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.

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.

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 ERP44 expression levels. Additionally, pan-cancer analysis was conducted to evaluate ERP44 expression and its prognostic value across different cancer types. The analysis identified several DEGs with significant prognostic value, including ERP44, which was significantly associated with poor prognosis in HNSC patients. High ERP44 expression correlated with reduced overall survival, disease-specific survival, and progression-free interval. ERP44 was notably overexpressed in tumor tissues and associated with key oncogenic pathways and immune cell infiltration patterns. Chemotherapeutic drug sensitivity analysis revealed that high ERP44 expression increased sensitivity to Paclitaxel, Vinblastine, and Sorafenib but decreased sensitivity to Rapamycin. Pan-cancer analysis indicated that ERP44 is differentially expressed and prognostic across multiple cancer types. Our findings highlight the crucial role of redox metabolism-related DEGs, particularly ERP44, in HNSC progression and prognosis. ERP44 serves as a potential biomarker for prognosis and therapeutic response, warranting further research into its biological functions and potential as a therapeutic target.

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.

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.

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.

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 Dubosiella, Faecalibaculum, Clostridia_UCG-014, Bifidobacterium, and Alloprevotella, while increase the abundances of Lactobacillus, Alistipes, and Lachnospiraceae in intestine. The results of correlation analysis showed that in hippocampus, Bifidobacterium was positively correlated with serine and glycine, while Alistipes 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.

Microvesicles (MV) isolated from septic individuals were observed to impact systemic hemodynamics and cardiac function. The aim of this in vitro study was to analyze the effects of TNFα-induced endothelial MV (TMV) and MV from septic patients (SMV) on beating frequency and Ca²⁺ 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 Ca²⁺ transients were measured in hiPSC-CM using the Ca²⁺-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 × 10⁶ 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 Ca²⁺ transients under these experimental settings. MV isolated from control or TNFα-treated HPMEC affected Ca²⁺ 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.

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) (P = 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; P = 0.007). RCS revealed that there was a linear association between Ln (SII) and the FRS (P for non-linearity = 0.972). As Ln (SII) increased, the value of FRS rose gradually (P 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.

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.