Mostafa A. Abdel-Maksoud

Integrative network analysis identifies candidate genes shared between ferroptosis and cuproptosis pathways in rheumatoid arthritis pathogenesis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation, progressive joint destruction, and systemic immune dysregulation. Recent findings suggest that disturbed metal homeostasis and regulated cell death pathways, including ferroptosis (iron-dependent lipid peroxidation) and cuproptosis (copper-dependent mitochondrial proteotoxic stress), contribute to RA pathogenesis. In this study, we used an integrative bioinformatic approach combining weighted gene co-expression network analysis (WGCNA), differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and immune cell infiltration deconvolution to identify key metal-dependent cell death regulators in RA. Using bulk RNA-seq data from peripheral CD14+ monocytes (GSE294225) from 15 healthy controls and 9 patients with active RA (DAS28 > 2.7), we identified 1,410 significantly differentially expressed genes (DEGs) (adjusted P < 0.05, log2 fold change > 1). WGCNA revealed an RA-associated module enriched in oxidative stress, mitochondrial dysfunction, and cell death pathways. Overlap analysis of ferroptosis- and cuproptosis-related gene sets distinguished three upregulated hub genes, including FTH1 (ferritin heavy chain 1), SOD2 (superoxide dismutase 2), and CDKN2A (cyclin-dependent kinase inhibitor 2A) as key candidate regulators. These genes showed high module membership, significant differential expression in RA monocytes, and notable associations with immune infiltration patterns, including increased pro-inflammatory monocytes/macrophages and reduced regulatory T cells. Functional enrichment also highlighted oxidative stress response, iron and copper homeostasis, mitochondrial respiration, and cellular senescence. The single-cell analysis further showed that these hub genes are predominantly expressed in the RA synovial macrophages and fibroblasts, two major mediators of joint pathology. Together, these findings indicate that there may be an association between ferroptosis-related pathways and cuproptosis-related pathways in RA and suggest that FTH1, SOD2, and CDKN2A are candidate biomarkers and candidate therapeutic targets.

Box-Behnken-Optimized Bacterial Nanocellulose-Silver and Zinc Oxide Nanocomposites: Bactericidal Activity, Antioxidant Capacity, Cytotoxicity, and In vitro Wound Healing Assessment.

Cadherin-mediated cell adhesion networks drive tumor growth and therapeutic responses in head and neck cancer.

BACKGROUND Cadherin family genes (CDH1, CDH2, and CDH3) regulate cell-cell adhesion and epithelial integrity and have emerging roles in tumorigenesis. However, their molecular and functional relevance in Head and Neck Squamous Cell Carcinoma (HNSC) remains incompletely defined. METHODS Cadherin expression was evaluated in HNSC and normal oral epithelial cell lines using RT-qPCR. Multi-omics analyses of transcriptomic, methylation, mutation, and copy number variation (CNV) data were performed using TCGA datasets through GSCA, OncoDB, cBioPortal, and UALCAN. Prognostic significance was assessed using Kaplan-Meier and meta-analysis approaches. miRNA-mRNA interactions were predicted using miRNet and validated experimentally. Immune associations, drug sensitivity, and protein-protein interactions were explored using TISIDB, GSCA, STRING, and DAVID. Functional effects of CDH1 and CDH2 were evaluated by siRNA knockdown in FaDu and SCC9 cells, followed by proliferation, colony formation, wound healing, and xenograft assays. RESULTS CDH1, CDH2, and CDH3 were significantly upregulated in HNSC cell lines and TCGA tumor samples, with CDH3 showing the highest diagnostic accuracy (AUC = 0.90). Hypomethylation and CNV amplification contributed to cadherin dysregulation, particularly for CDH2 and CDH3. Elevated cadherin expression correlated with poor overall survival. miR-200a-3p and miR-200c-3p were identified as shared regulators. Cadherin expression also showed associations with immune modulators and drug response. Functionally, CDH1 and CDH2 knockdown suppressed proliferation, migration, and tumor growth. CONCLUSION Cadherin genes, particularly CDH3, show diagnostic and prognostic relevance in HNSC, while CDH1 and CDH2 contribute to tumor cell growth and migration. Further studies are required to determine their therapeutic potential.

Computational insights into the inhibitory potential of cyclotides Psyle B and Psyle C against key surface proteins of avian influenza H5N1.

This study explored cyclotide-based drug design against H5N1 using computational approaches and revealed that Psyle B and Psyle C exhibited strong interactions with HA and NA, highlighting Psyle B and Psyle C as promising antiviral leads.