Roles of pyroptosis and immune infiltration in aortic dissection.

Introduction: Aortic dissection (AD) is often fatal, and its pathogenesis involves immune infiltration and pyroptosis, though the molecular pathways connecting these processes remain unclear. This study aimed to investigate the role of immune infiltration and pyroptosis in AD pathogenesis using bioinformatics analysis. Methods: Two Gene Expression Omnibus datasets and a Gene Cards dataset of pyroptosis-related genes (PRGs) were utilized. Immunological infiltration was assessed using CIBERSORT, and AD diagnostic markers were identified through univariate logistic regression and least absolute shrinkage and selection operator regression. Interaction networks were constructed using STRING, and weighted gene correlation network analysis (WGCNA) was employed to identify important modules and essential genes. Single-sample gene set enrichment analysis determined immune infiltration, and Pearson correlation analysis assessed the association of key genes with infiltrating immune cells. Results: Thirty-one PRGs associated with inflammatory response, vascular epidermal growth factor receptor, and Rap1 signaling pathways were identified. WGCNA revealed seven important genes within a critical module. CIBERSORT detected immune cell infiltration, indicating significant changes in immune cell infiltration and pyroptosis genes in AD and their connections. Discussion: Our findings suggest that key PRGs may serve as indicators for AD or high-risk individuals. Understanding the role of pyroptosis and immune cell infiltration in AD pathogenesis may lead to the development of novel molecular-targeted therapies for AD. Conclusion: This study provides insights into the molecular mechanisms underlying AD pathogenesis, highlighting the importance of immune infiltration and pyroptosis. Identification of diagnostic markers and potential therapeutic targets may improve the management of AD and reduce associated morbidity and mortality.

The capillary-leakage syndrome caused by glyphosate poisoning: a case report.

Glyphosate is widely used in agriculture even though it can cause self-poisoning, inducing gastrointestinal disturbance, acute respiratory distress syndrome, arrhythmia, renal failure, and even death. Case presentation: The authors present a case of glyphosate poisoning in a patient who developed capillary-leak syndrome, severe metabolic acidosis, and shock. After treatment with hemoperfusion and continuous renal replacement therapy, the patient was extubated after 7 days and transferred out of the intensive care unit after 10 days. Clinical discussion: Severe glyphosate poisoning can lead to multiple organ failure and systemic capillary leak syndrome. Clinical manifestations of systemic capillary leak syndrome included hemoconcentration, increased hematocrit, hypoalbuminemia, interstitial fluid accumulation, and refractory hypotension. Substantial improvement of capillary leakage was observed only gradually after initiation of early continuous renal replacement therapy, plasma infusion, and application of ulinastatin. Conclusions: This case report highlights the life-threatening nature of glyphosate poisoning. Aggressive treatment and careful monitoring of complications are required, particularly in patients at risk of capillary leakage syndrome.

Treatment with paraquat affects the expression of ferroptosis-related genes.

OBJECTIVE: We aimed to explore the mechanisms underlying paraquat (PQ)-induced damage using cell lines (NCTC1469, TC-1, TCMK-1) and bioinformatic analysis of the GSE153959 dataset. Assessment of changes in the expression of ferroptosis-related genes in cellular damage due to paraquat poisoning and the important value of these genes in the pathogenesis. METHODS: Data were retrieved from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) related to ferroptosis were identified by Venn plots and analyzed for enrichment. Proteins encoded by these DEGs were studied for interactions. qRT-PCR and western blotting analyses of cultured cells were used to determine the expression of ferroptosis-related DEGs and their corresponding protein levels. RESULTS: We identified 25 DEGs primarily involved in epidermal growth factor receptor signaling, apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and ferroptosis. From these, we uncovered eight ferroptosis-related DEGs, four of which were involved in ER response and regulators of ferroptosis-Chac1 (ChaC glutathione specific gamma-glutamylcyclotransferase 1), Atf3 (activating transcription factor 3), Tfrc (transferrin receptor), and Slc7a11 (solute carrier family 7 member 11). Significant changes in mRNA and protein levels of CHAC1, ATF3, TFRC, and SLC7A11 were confirmed in PQ-exposed cells. CONCLUSION: ER stress and ferroptosis are critical for PQ-induced cell damage. CHAC1, ATF3, TFRC, and SLC7A11 are essential molecules implicated in PQ-induced ferroptosis that may serve as therapeutic targets for the amelioration of PQ poisoning.

WTAP regulates autophagy in colon cancer cells by inhibiting FLNA through N6-methyladenosine.

Our study investigated the role of WTAP in colon cancer. We employed experiments including m6A dot blot hybridization, methylated RNA immunoprecipitation, dual-luciferase, and RNA immunoprecipitation to investigate the regulatory mechanism of WTAP. Western blot was performed to analyze the expression of WTAP, FLNA and autophagy-related proteins in cells. Our results confirmed the up-regulation of WTAP in colon cancer and its promoting effect on proliferation and inhibiting effect on apoptosis. FLNA was the downstream gene of WTAP and WTAP-regulated m6A modification led to post-transcriptional repression of FLNA. The rescue experiments showed that WTAP/FLNA could inhibit autophagy. WTAP-mediated m6A modification was confirmed to be crucial in colon cancer development, providing new insights into colon cancer therapy.

Bioinformatics Analysis Based on TCGA: MUC16 Mutation Correlates with Clinical Outcome in Gastric Cancer.

The prognosis of gastric cancer (GC) is difficult to predict due to the disease's complex genetic and phenotypic characteristics. MUC16 has been reported to be involved in the progression of several tumors. In this study, we aimed to explore whether MUC16 mutation had any impact on the prognosis or treatments of GC patients. Additionally, this analysis uncovered possible critical pathways related with these systems. On the cBioPortal, we were able to locate the pertinent data of patients with MUC16 mutations. And then, GSEA analysis identified differences in mRNA levels between mutant and wild-type MUC16 patients in terms of biological function annotation and pathways. The KEGG and GO analyses were also performed using the differentially expressed genes (DEGs). There were 139 individuals with GC who had the MUC16 mutation, which accounts for 32 percent, and the remaining patients had the MUC16 wild type. Survival assays revealed that patients with the MUC16 mutation had longer overall survival and disease-free survival. GSEA analysis revealed that cell cycle, cysteine and methionine metabolism, Huntington's disease, one carbon pool by folate, pyrimidine metabolism, pyruvate metabolism, RNA degradation, spliceosome, and valine leucine and isoleucine degradation were distinctly enriched in patients with MUC16 mutation type. Moreover, we identified 323 DEGs. Among them, 162 genes were upregulated, and 161 genes were downregulated. GO and KEGG assays indicated DEGs as enriched in pancreatic secretion, neuroactive ligand-receptor interaction, protein digestion and absorption, fat digestion and absorption, and glycerolipid metabolism. Overall, our data revealed that the MUC16 mutation in GC may affect the development of patients by altering several genes and pathways, indicating the importance of MUC16 mutation in the treatments of GC on an individual basis.

AK001058 promotes the proliferation and migration of colorectal cancer cells by regulating methylation of ADAMTS12.

BACKGROUND: Long noncoding RNA (LncRNA) functions as multiple mechanisms, including DNA methylation in colorectal cancer (CRC). ADAMTS12 was applied as biomarkers in CRC via abnormally DNA methylation. Lnc-AK001058 gene, which was reported dysregulated in CRC, is located adjacent to the gene ADAMTS12. However, little is known about the role of AK001058 during the proliferation and migration of CRC. MATERIAL AND METHODS: In present study, quantitative RT-PCR were used to measure AK001058 and ADAMTS12 expression levels, and western blotting assays were performed to measure ADAMTS12 expression in CRC cells. Methylation-specific PCR (MSP) was applied to measure the methylation of the CpG islands of the ADAMTS12 promoter. Cell proliferation, migration, invasion and cycle assays ware utilized to analyze the role of AK001058 in CRC. RESULTS: The results indicated that the expression of AK001058 was significantly increased in CRC. Overexpression of AK001058 could suppress the expression of ADAMTS12. AK001058 also significantly promoted cell proliferation, migration and invasion, and prolonged S stage of CRC, while silencing the expression of AK001058 showed contrary effects. Moreover, compared with negative control and AK001058-NC groups, overexpression of AK001058 could increase the DNA methylation level of ADAMTS12 gene promoter in CRC, while si-AK001058 could reverse this effect. CONCLUSION: In conclusion, AK001058 promotes the proliferation, invasion, migration, and prolonged S stage of CRC by regulating methylation of ADAMTS12. Our research will provide new insights for the biomarker of colorectal cancer diagnose and new clues for clinical treatment.

Long non-coding RNA AK001058 regulates tumor growth and angiogenesis in colorectal cancer via methylation of ADAMTS12.

Colorectal cancer, a common gastrointestinal malignant tumor, has been a leading cause of cancer related deaths. Long non-coding RNAs (lncRNAs) play an important role in regulating cancer development. The aim of this study was to investigate the role and potential mechanism of lncRNA AK001058 in colorectal cancer. To establish tumor xenografts, BALB/c nude mice received subcutaneously injection of SW480 cells with transfection targeting AK001058 (overexpression or knockdown). Tumor growth was observed and recorded. The relative gene expression levels were determined by quantitative real-time PCR or western blot. Cell apoptosis was determined by tunnel analysis. Microvessel morphology changes were detected by H&E staining. Methylation level of CpG island was analyzed using methylation specific PCR. The results showed that AK001058 overexpression notably accelerated tumor growth. AK001058 overexpression also decreased cell apoptosis, worsened microvessel morphology and increased the expression of VEGFA and angiopoietin II. Moreover, AK001058 decreased the expression of ADAMTS12 by increasing its methylation level. Nevertheless, AK001058 knockdown exerted the opposite function. Therefore, AK001058 knockdown could effectively inhibit tumor growth mostly accounting for decreased cell apoptosis and tumor angiogenesis, which was partly dependent on the high methylation level of ADATS12. These data provided a novel therapeutic strategy of colorectal cancer.