Apmis最新文献

This study aimed to investigate the role of YTHDF1, a key m6A reader protein, in ulcerative colitis (UC) pathogenesis and its potential involvement in ferroptosis through ACSL4 regulation. Clinical serum and tissue samples from UC patients, as well as dextran sulfate sodium (DSS)- and oxazolone (OXZ)-induced colitis mouse models, were used to assess YTHDF1 expression and its correlation with disease severity. Ferroptosis markers, including reactive oxygen species (ROS), lipid peroxidation products, and iron levels, were assessed in both colonic tissues and DSS-treated Caco-2 cells. RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to explore YTHDF1-mediated mRNA stabilization of ACSL4. Data showed that YTHDF1 was significantly upregulated in the serum and colonic tissues of UC patients, with expression levels correlating positively with disease severity. In UC mouse models, YTHDF1 expression was increased, and its knockdown reduced colitis severity. Mechanistically, YTHDF1 knockdown suppressed ferroptosis by reducing lipid peroxidation, ROS accumulation, and iron overload. Additionally, ACSL4, a key ferroptosis regulator, was identified as a downstream target of YTHDF1, with YTHDF1 stabilizing ACSL4 mRNA through m6A modifications. Collectively, YTHDF1 promotes ferroptosis in UC by stabilizing ACSL4 mRNA through m6A modifications and highlights its potential as a therapeutic target for UC treatment.

Prostate cancer is the most common malignancy among men worldwide, and treatment response depends on tumor radiosensitivity. Micrornas (mirnas) are key regulators of cell proliferation, apoptosis, and dna damage response, and have been implicated in therapy resistance. However, their roles in prostate cancer radioresponse remain incompletely understood. This study investigated the expression patterns of ten selected mirnas associated with radiation resistance in other cancers in prostate cancer models. Radiation-resistant pc-3, radiation-sensitive lncap, and normal prostate epithelial (hprec) cells were exposed to 0, 2, 4, 6, and 8 gy of ionizing radiation. Mirna expression levels were analyzed by quantitative pcr using snord48 as an internal control and calculated with the 2 − δδct method. In pc-3 cells, mir-20a-5p, mir-128-3p, and mir-135b-5p showed significant dose-dependent upregulation, whereas mir-23b-3p and mir-381-3p were downregulated. Mir-128-3p correlated positively with radiation dose, while mir-23b-3p and mir-381-3p showed negative correlations. Lncap cells exhibited moderate, non–dose-dependent mirna changes. Distinct mirna signatures differentiate radiation-resistant and radiation-sensitive prostate cancer cells. Mir-20a-5p, mir-128-3p, and mir-135b-5p may contribute to radioresistance, whereas mir-23b-3p and mir-381-3p may act as radiosensitizers.

Developing natural alternatives to antibiotics is an essential aspect for countering bacterial pathogens. This study focused on the influence of plant-derived extracts on biofilm and quorum-sensing (QS) inhibition in Pseudomonas aeruginosa. On screening, the methanolic extract (ME) of Sapindus mukorossi (Sm-ME) effectively inhibited biofilm formation. The major bioactive groups present in Sm-ME were alkaloids, flavonoids, terpenoids, and saponins. These phytochemicals were validated by biochemical, Fourier transform infrared spectroscopy, and gas chromatography–mass spectroscopy analysis. Sm-ME significantly inhibits up to 82.5% of P. aeruginosa biofilm formation and anti-QS activity in a dose-dependent manner. The microscopy analysis and the down-regulation of virulence genes (lasI, lasR, rhII, and rhIIR) validated the effectiveness of Sm-ME in P. aeruginosa inhibition. Additionally, Sm-ME retained good biocatalytic activity on exposure to high temperatures up to 90°C and higher antioxidant activity than ascorbic acid. These findings briefly demonstrated the potential influence of Sm-ME for combating biofilm and QS inhibitions in P. aeruginosa via a natural, sustainable alternative to antibiotics.

Significant heterogeneity in the immune microenvironment of Glioblastoma, IDH-wildtype (GBM), has been reported, necessitating a standardized approach to evaluate immune infiltration in the context of emerging immunotherapies. To address this, we developed and validated a standardized immunohistochemistry-based scoring system for quantifying immune cell infiltration in formalin-fixed, paraffin-embedded (FFPE) tissue. Paired primary and recurrent GBM specimens from 20 adult patients were labeled for CD3, CD8, CD45, CD68, and PD-1, and scored across six anatomical regions, including intra- and peritumoral, meningeal, and normal brain areas. The scoring system demonstrated excellent interrater (ICC = 0.932) and intrarater (ICC = 0.953) reliability. CD68+ and CD45+ cells were most numerous across all regions. CD3+ and CD8+ cells concentrated more in the perivascular area rather than within the parenchyma. No significant differences in immune infiltration were observed between primary and recurrent GBM. Cox proportional-hazards analysis showed worse survival with higher CD8+ and CD45+ infiltration in primary GBM, and higher CD45+ and CD68+ infiltration in recurrent GBM. In conclusion, we propose a feasible, cost-efficient, and robust method to assess immune infiltration on FFPE material, enabling standardized comparison of inflammation, with applications for ongoing clinical trials.

The effect of human coronaviruses (HCoVs) on airway epithelial cells is known and very well described. However, their influence on the human lung endothelium remains poorly understood. In this study, we assess the effect of low pathogenic HCoV-229E on the inflammatory and antiviral response of Human Lung Microvascular Endothelial Cells (HMVEC-L). Human Lung Microvascular Endothelial Cells were infected with HCoV-229E and then mRNA expression, protein release, cell viability, apoptosis rate, and presence of AP-N in flow cytometry were assessed. The infection of HMVEC-L with HCoV-229E led to the massive replication picked at 96 h post infection (hpi); however, the virus efficiently replicated at 48 hpi. Despite the inflammatory (IL-8, IL-6) and antiviral (IFN-β, OAS-1, PKR, MX-1) response, as well as the pattern recognition receptors activation (TLR3, TLR7/8, RIG-I, MDA5) occurred only at hour 72. Additionally, the cytopathic effect and the increase in apoptosis were observed. AP-N blockade inhibited inflammatory and antiviral induction, as well as decreased HCoV-229E genome copy numbers in HMVEC-L. We proved that the lung microvascular endothelium may be infected by human coronavirus 229E and that this infection may lead to a robust, but delayed inflammatory and antiviral response. Secondly, HMVEC-L may play an important role during Coronaviridae upper and lower airway infections.

This study investigated whether Sevoflurane preconditioning (Sevo-pre) attenuates hypoxia/reoxygenation (H/R)-triggered myocardial damage by targeting microRNA-451a (miR-451a) and its downstream target interleukin 6 receptor (IL6R). Rat embryonic cardiomyoblast-derived H9C2 underwent H/R injury modeling with either Sevo-pre or no preconditioning. Mechanistic studies employed the manipulation of miR-451a overexpression and silencing, alongside IL6R modulation via targeted siRNA and plasmid transfection. Sevo-pre significantly enhanced cell viability, reduced apoptosis, and decreased injury markers in H/R-induced cells (p < 0.001). Notably, miR-451a was downregulated in H/R conditions but upregulated by Sevo-pre. The inhibition of miR-451a negated Sevo's protective effects, exacerbating oxidative stress and apoptosis (p < 0.001). Bioinformatics analyses and luciferase assays identified IL6R as a direct target of miR-451a. Silencing IL6R mitigated the adverse effects of miR-451a inhibition, restoring cell viability and reducing oxidative stress (p < 0.001). Sevo-pre alleviates H/R injury in cardiomyocytes through the regulation of miR-451a, which suppresses IL6R expression, consequently reducing oxidative stress and apoptosis. This study elucidates a novel cardioprotective mechanism of preconditioning via the miR-451a/IL6R axis, which highlights miR-451a and IL6R as potential therapeutic targets for mitigating myocardial I/R injury in clinical settings.

circRNAs play pivotal roles in cancer initiation and progression. To explore the metastasis-related circRNA-miRNA-mRNA network in ESCC for novel biomarkers and therapeutic targets, differentially expressed circRNAs, miRNAs, and mRNAs were obtained from GEO datasets. A metastasis-associated circRNA-miRNA-mRNA ceRNA network in ESCC was constructed using Cytoscape software. The STRING database and Cytoscape were utilized for protein–protein interaction (PPI) interaction generation. The GEPIA2 database was used to obtain the expression of downstream targets and their prognostic value. The GO and KEGG enrichment analyzes were performed using the DAVID database. A dual-luciferase reporter assay was utilized to validate the target interaction among hsa_circ_0007551, miR-493-5p, and CXCL8/BMP2. Six metastasis-related DEcircRNAs overlapped from the GSE131969 and GSE150476 datasets. The ceRNA network was constructed containing six circRNAs, 15 miRNAs, and 86 mRNAs. In the ceRNA network, CXCL8 and BMP2, which were significantly associated with overall survival in ESCC patients, were chosen for further subnetwork construction. Then, a metastatic and survival-related ceRNA network containing hsa_circ_0007551, miR-493-5p, and two DEGs (CXCL8 and BMP2) was identified. hsa_circ_0007551 was upregulated in ESCC tissues and cells. In conclusion, this study identified novel circRNA-mediated ceRNA networks in ESCC metastasis, highlighting hsa_circ_0007551 and the CXCL8/BMP2 axis as potential biomarkers and therapeutic targets.

Fusobacterium nucleatum (Fn), an intratumoral pathogenic bacterium, is confirmed to be associated with tumor progression in colorectal cancer (CRC). To evaluate CD8⁺ T cell function against CRC cells, their cytotoxicity was determined via live/dead staining and ELISA, while proliferation was assessed using the CFSE assay. CD274 (PD-L1) expression in CRC was quantified by qPCR, flow cytometry, and immunofluorescence. Lactate accumulation in CRC cells was measured using LDHA and lactate assay kits. Histone lactylation levels were analyzed by Western blot. Chromatin immunoprecipitation was applied to examine the abundance of H3K18 lactylation (H3K18la) at the CD274 promoter region. Finally, Annexin V/PI staining was employed to analyze the apoptosis rate of CRC cells. Fn treatment inhibited the anti-tumor immune capacity of CD8⁺ T cells against CRC cells and increased PD-L1 expression. Fn stimulation promoted lactate accumulation in CRC cells and enhanced H3K18la levels. Mechanistic studies revealed enrichment of H3K18la. Fn treatment induced H3K18la of PD-L1, upregulating its expression, suppressing CD8⁺ T cell immune activity, and promoting immune escape in CRC. This study demonstrates that Fn is crucial in CRC immune escape, proposing that regulating Fn abundance represents a novel strategy to enhance immunotherapy effectiveness.

Microbiologically influenced corrosion (MIC) is a significant issue causing material damage of metals in pipelines, storage tanks, and marine infrastructure, leading to significant industrial damage and maintenance costs. Anaerobic sulfate-reducing bacteria (SRB) are the main causative agent for MIC. Their capacity to form biofilms facilitates SRB to cause high corrosion rates. In this study, Ag–SiO₂ nanocomposite with silver nanoparticle (Ag NP) dispersed in the silicon dioxide (SiO₂) matrix was synthesized using a one–pot sol–gel method. Ag–SiO₂ NC was evaluated for its capacity to deter biofilm formation and impact the transcript gene expression of key markers HydA and DVU1817 Cytochrome c553 genes for the SRB biofilm-formation and metal corrosion in Desulphovibrio gigas strain. The effect of Ag–SiO₂ NC on the SRB mediated Carbon steel corrosion was also examined using potentiodynamic polarization electrochemical corrosion testing. The findings from our study validate the antibacterial and corrosion inhibitory characteristics of nanocomposite Ag–SiO₂ NC against D. gigas. A simple and reproducible Ag–SiO₂ NC synthesis will significantly boost the industrial production of silver-doped silica products for controlling SRB population, enabling development of advanced high-performance protective metal coatings with enhanced antimicrobial properties.