The emergence of Candida albicans as a life-threatening pathogen and its resistance to available antifungal drugs is a significant global health concern. Previous findings have established that the ub Show more
The emergence of Candida albicans as a life-threatening pathogen and its resistance to available antifungal drugs is a significant global health concern. Previous findings have established that the ubiquitin mutations UbEP42, UbL50P and UbI61T interfere with morphogenesis of C. albicans from commensal yeasts to pathogenic hyphae. The main objective of this study is to investigate the influence of ubiquitin mutations on the molecular markers of morphogenesis and virulence of C. albicans to identify potential targets for therapeutic intervention. The auxotrophic strain BWP17 of C. albicans was transformed by the wild-type ubiquitin gene (UbWT) and its mutants UbEP42, UbS20F, UbA46S, UbL50P and UbI61T cloned under the doxycycline-inducible promoter in the integrative plasmid pTET25-MNC. Induced expression of the mutant forms UbEP42, UbL50P, and UbI61T while inhibiting morphogenesis, reduced chitin deposition, increased β-glucan exposure on the cell wall, decreased the secretion of aspartyl protease, caused the differential expression of cyclins Cln3, Ccn1, Clb2 and certain key transcription factors compared to UbWT. However, UbS20F and UbA46S did not have any influence. These findings demonstrating the disruptive influence of UbEP42, UbL50P, and UbI61T on the levels of molecular markers of morphology and pathogenesis of C. albicans, highlight the importance of a functional ubiquitination system. Show less
Alzheimer's disease (AD) is an advancing neurodegenerative disorder distinguished by the formation of amyloid plaques and neurofibrillary tangles in the human brain. Nevertheless, the lack of peripher Show more
Alzheimer's disease (AD) is an advancing neurodegenerative disorder distinguished by the formation of amyloid plaques and neurofibrillary tangles in the human brain. Nevertheless, the lack of peripheral biomarkers that can detect the development of AD remains a significant limitation. The main aim of this work was to discover the molecular markers associated with AD. We conducted a comprehensive microarray analysis of gene expression data from hippocampus tissue in AD patients and control samples using three microarray datasets (GSE1297, GSE28146, and GSE29378) collected from Gene Expression Omnibus (GEO). The datasets were pre-processed and normalized, revealing 346 significant genes, 103 of which were upregulated and 243 downregulated. The PPI network of significant genes was constructed to detect the top 50 hub genes, which were then further analyzed using Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and GSEA, revealing 47 key genes involved in AD-related pathways. These key genes were then subjected to feed forward loop (FFL) motif analysis for the prediction of transcriptional factors (TFs) and microRNAs (miRNAs) mediated gene regulatory networks. The interaction of AD-associated TFs HNF4A, SPI1, EGR1, STAT3, and MYC and miRNAs hsa-miR-155-5p and hsa-miR-16-5p in the transcriptional and post-transcriptional events of 3 upregulated and 10 downregulated genes: H2AFZ, MCM3, MYO1C, AXIN1, CCND1, ETS2, MYH9, RELA, RHEB, SOCS3, TBL1X, TBP, TXNIP, and YWHAZ, respectively, has been identified. The miRNA/TF-mediated three types of the FFL motifs, i.e., miRNA-FFL, TF-FFL, and composite-FFL, were constructed, and seven common genes among these FFL were identified: CCND1, MYH9, SOCS3, RHEB, MYO1C, TXNIP, AXIN1, and TXNIP. These findings may provide insights into the development of potential molecular markers for therapeutic management of AD. Show less