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Objectives: Fibroleukin (FGA) and NOTCH3 are vital in both exercise-induced muscle adaptation and colon adenocarcinoma (COAD) progression. This study aims to elucidate the roles of FGA and NOTCH3 in phenotypic variations of striated muscle induced by exercise and in COAD development. Additionally, it seeks to evaluate the prognostic significance of these proteins. Methods: Gene Set Variation Analysis (GSVA) and protein-protein interaction (PPI) network analysis were employed to identify differentially expressed genes (DEGs). Molecular docking studies were conducted to assess the binding affinities of 39 compounds to the NOTCH3 protein. In vitro assays, including mobileular viability, gene expression, and apoptosis assays, were performed to evaluate the effects of glycerophosphoinositol on FGA and NOTCH3 expression. Additionally, copy number variation (CNV), methylation status, and survival analyses were conducted across multiple cancers types. Results: The NOTCH signaling pathway was consistently upregulated in exercise-induced muscle samples. High NOTCH3 expression was associated with poor prognosis in COAD, extracellular matrix organization, immune infiltration, and activation of the PI3K-Akt pathway. Molecular docking identified gamma-Glu-Trp, gamma-Glutamyltyrosine, and 17-Deoxycortisol as strong binders to NOTCH3. Glycerophosphoinositol treatment modulated FGA and NOTCH3 expression, influencing cell proliferation and apoptosis. CNV and methylation analyses revealed specific changes in FGA and NOTCH3 across 20 cancers types. Survival analyses showed strong associations between FGA/NOTCH3 expression and survival metrics, with negative correlations for FGA and positive correlations for NOTCH3. Conclusion: FGA and NOTCH3 play significant roles in exercise-induced muscle adaptation and colon cancer progression. The expression profiles and interactions of these proteins provide promising prognostic markers and therapeutic targets. These findings offer valuable insights into the post-translational modifications (PTMs) in human cancer, highlighting novel pharmacological and therapeutic opportunities.

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Background: Bicaudal-D (BICD) Family Like Cargo Adaptor 1 (BICDL1) is an essential component of the molecular mechanism during neuronal development. However, BICDL1 has not been reported in cancer. Using bioinformatics analysis, we systematically evaluated the potential role of BICDL1 in CRC. Methods: Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan-Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells. Results: BICDL1 had a higher expression in CRC tissues than in normal tissues (p < 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07-2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895-0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p <0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p <0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=-0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p <0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p < 0.001). Conclusion: BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.

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Background: Despite the association of ferroptosis with various tumors, the specific mechanism by which it influences colon adenocarcinoma (COAD) microenvironmental equilibrium remains elusive. This study aims to elucidate how ferroptosis affects COAD microenvironmental homeostasis and its potential impact on COAD research. Objective: By employing genetic screening and single-cell analysis of tumor data, we investigated the role of ferroptosis genes in COAD microenvironmental homeostasis. The genes were correlated with immune cell infiltration in tissue samples and patient outcomes. Methods: Ferroptosis-associated genes were initially identified through the FerrDb database. Utilizing the tidyverse and Seurat packages, genes with substantial expression differences were extracted, and clustering analysis was performed on the single-cell data. A Venn diagram depicted shared differential genes for ferroptosis and tumors. To screen key ferroptosis genes, further enrichment analysis and immune cell infiltration analysis were conducted. Lastly, human COAD cell lines were employed to overexpress CDGSH iron sulfur domain 2 (CISD2) through cellular assays to validate its function in COAD. Results: Following screening of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, 414 COAD patient samples and 341 normal samples were included. Through the FerrDb database, 259 ferroptosis genes were identified. Clustering the single-cell data revealed 911 tumor marker genes, of which 18 were ferroptosis genes. Analysis of variance (ANOVA) and univariate regression analysis determined that only CISD2 was statistically significantly associated with clinical outcomes. Additionally, CISD2 was found to positively correlate with activated memory T cells and negatively correlate with regulatory T cells (Tregs) and plasma cells in COAD, as well as being significantly associated with several immune-related and cancer-related pathways. CISD2 expression was elevated in most tumors, likely due to cell cycle regulation and immune system activation. Moreover, CISD2 upregulation inhibited COAD cell proliferation and enhanced 5-fluorouracil (5-FU) sensitivity. Our findings indicate, for the first time, that CISD2 governs the cell cycle and stimulates the immune system to impede COAD progression. Conclusion: By modulating the cell cycle and mediating immune infiltration, CISD2 may inhibit COAD development by influencing tumor immune microenvironment equilibrium, providing valuable insights into the relevance and potential impact of the research results on the COAD research field.

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Background: In recent years, the incidence and mortality of colorectal cancer (CRC) are increasing, and the 5-year survival rate of advanced metastatic CRC is poor. Small mothers against decapentaplegic (SMAD) superfamily are intracellular signal transduction proteins associated with the development and prognosis of a variety of tumors. At present, no study has systematically analysed the relationship between SMADs and CRC. Methods: Here, R3.6.3 was used to analyse the expression of SMADs in pan-cancer and CRC. Protein expression of SMADs were analysed by Human Protein Atlas (HPA). Gene expression profiling interactive analysis (GEPIA) was used to evaluate the correlation between SMADs and tumor stage in CRC. The effect of R language and GEPIA on prognosis was analysed. Mutation rates of SMADs in CRC were determined by cBioPortal, and potentially related genes were predicted using GeneMANIA. R analysis was used to correlate immune cell infiltration in CRC. Results: Both SMAD1 and SMAD2 were found to be weakly expressed in CRC and correlated with the immune invasion level. SMAD1 was correlated with patient prognosis, and SMAD2 was correlated with tumor stage. SMAD3, SMAD4, and SMAD7 were all expressed at low levels in CRC and associated with a variety of immune cells. SMAD3 and SMAD4 proteins were also expressed at low levels, and SMAD4 had the highest mutation rate. SMAD5 and SMAD6 were overexpressed in CRC, and SMAD6 was also associated with patient overall survival (OS) and CD8+ T cells, macrophages, and neutrophils. Conclusions: Our results reveal innovative and strong evidence that SMADs can be used as biomarkers for the treatment and prognosis of CRC.

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BACKGROUND: Colorectal adenoma (CRA) is the main cause of the progression of Colorectal adenocarcinoma (COAD). Therefore, it is very important to accurately reveal its developmental mechanism. METHODS: Differential expression genes (DEGs) in three microarray datasets were screened using GEO and GEO2R. R packages were used for gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) path enrichment analysis. Hub genes screened by STRING, Cytoscape and CytoHubba were used. R was used for DEGs of hub genes, and Gene Expression Profiling Interactive Analysis (GEPIA2) database was used for prognostic Analysis. R-packet were used to analyze tumor pathology, tumour, lymph-nodes, and metastases (TNM) staging, enrichment, immune invasion and prognosis. RESULTS: Among the 66 genes, including 36 up-regulated and 30 down-regulated genes. Survival analysis showed that COL1A1, COL5A2, COL5A1 and secreted protein acidic and rich in cysteine (SPARC) were associated with disease-free survival in patients. The four genes were related to tumor pathological stage, TNM stage and immune invasion. COL1A1 and COL5A2 were highly expressed in chromatin modification and cellular senescence. Low expression of COL5A1 and SPARC was significantly enriched in neutrophil degranulation and Wp VegfavegFR2 signaling pathways. CONCLUSIONS: Obviously, these four key genes can serve as important targets for early diagnosis, treatment, immunity and prognosis of CRA to COAD.

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The purpose of this study was to evaluate the intervention effect of evidence-based nursing (EBN) on vacuum sealing drainage (VSD) recovery of patients with high perianal abscess after vacuum sealing drainage based on magnetic resonance imaging (MRI) sequence images. 60 patients with high perianal abscess were selected, and 30 patients before VSD were selected as the control group. Routine nursing was implemented in the control group, 30 patients after VSD were observed, and EBN was implemented in the observation group. The detection rates of various types of perianal abscess with different sequence combinations were studied, and the effects of EBN on pain and anal function scores of perianal abscess patients were analyzed. Anal function and defecation were assessed, and postoperative complications were calculated. Different combinations of MRI sequences can reach higher detection rates of intersphincter abscess and ischial anal abscess. The observation group had better pain relief and anal function recovery. The complication rate of the observation group was 16.67%, which was significantly lower than that of the control group (P < 0.05). It was confirmed that different MRI sequence combinations had higher detection rates for intersphincter abscess and ischial fossa abscess. EBN can promote the recovery of anal function and reduce complications in patients with perianal abscess.

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