An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

[Differentially expressed genes analysis in expression profile data of pulmonary fibrosis with pulmonary hypertension].

Objective: To analyze the differential gene expression of patients with idiopathic pulmonary fibrosis and pulmonary hypertension (IPF-PH). Methods: The expression profile data of GSE15197 was downloaded from the Gene Expression Omnibus (GEO) database. Bonferroni algorithm was used to identify the differentially expressed genes of pulmonary tissues from IPF-PH, idiopathic pulmonary arterial hypertension (IPAH) and Normal groups. Principal component analysis was used to extract the principal components of three types of samples and differentially expressed genes were obtained. Gene annotation and gene association analysis were used to analyze gene function and related signaling pathways. Results: Gene expression profiles of pulmonary tissues from IPF-PH, IPAH and Normal groups were compared and analyzed, and 160 differentially expressed genes were found (P<0.05). Nine principal component were found with the cumulative contribution rate of >0.85, and there were 44 significant differences genes with the loading coefficient >80% in principal component one, which was mainly related to the expression of cilium, gamma-glutamyltransferase, and phospholipase. The signaling pathway of differential expression genes were mainly involved in the biosynthesis of leukotriene biosynthetic process and gamma-glutamyltransferase activity. Conclusion: The differential gene expression and their functional annotation can provide important clues for the pathogenic genes of IPF-PH, and may provide a theoretical basis for exploring potential biomarkers and drug targets.

Alteration of endothelial nitric oxide synthase expression in acute pulmonary embolism: a study from bench to bioinformatics.

OBJECTIVE: This study sought to explore endothelial nitric oxide synthase (eNOS) expression in acute pulmonary thromboembolism (APE). MATERIALS AND METHODS: eNOS expression in lung tissue and bone marrow-derived endothelial progenitor cells (BM-EPCs) from APE mouse models was assessed by immunohistochemistry and real-time PCR. A gene expression profile meta-analysis was performed on human venous thromboembolism (VTE) whole blood samples recorded in the Gene Expression Omnibus (GEO) repository. Significantly expressed genes were determined from the microarray data by unsupervised clustering and supervised classification. Selected sample data with significantly expressed genes were further analyzed by principal component analysis (PCA), followed by Bayesian probit regression. Key discriminate genes were further grouped and annotated using functional annotations and gene enrichments using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) software (v. 6.7). RESULTS: While eNOS expression was significantly higher, serum nitric oxide levels were significantly lower in APE mice (20.42 ± 2.15 µM) compared to controls (53.50 ± 5.69 µM, p<0.001). eNOS mRNA and protein levels were significantly upregulated in BM-EPCs from APE mice. GEO repository data reported 3,397 upregulated and 4,173 downregulated genes (including eNOS) in VTE patients. In this regression analysis, the significant principal component PC1 and PC2 (p<0.05) were useful in distinguishing the VTE classification. The coefficient value of eNOS was -0.47707 in PC1 and -0.08429 in PC2, which did have some proportions on these significantly discriminated components but did not contribute significantly to the VTE classification. Functional enrichment in terms of acetylation and phosphoproteins were high. CONCLUSIONS: Our findings, therefore, suggest that expression of eNOS is significantly altered in APE and may be a potential peripheral blood biomarker. Modulation of eNOS expression may be used for APE treatment.