Suez Canal University

Aquatic environmental pollution could be a direct trigger of infection through cercarial invasion to skin / gills or indirectly as a predisposing factor that damage the physical barriers of targeted fish resulting in high intensities of EMC infections in all fish vital organs. In the current study, a total of 150 African catfish (Clarias gariepinus) were randomly collected from Mariotteya drain all the way through the Egyptian township of Shabramant located at the historical heart of Giza. Catfish samples were collected in mid-summer during the period from June to July 2024. A well-documented surge in unionized ammonia, water alkalinity, marked decline in dissolved oxygen together with decreased transparency were signaling a chronic case of agricultural and municipal pollution in which all physical mucosal immunological barriers were harshly suppressed. This environmental disruption has resulted in cellular, biological and pathological alterations in which the invasion of digenean cercariae was favored as documented in the histopathological sections made from affected tissues. Parasitological examination revealed the presence of two distinct EMC belonging to Prohemistomum vivax and Cyanodiplostomum spp. which were presumptively identified using the regular morpho-taxonomical methods and confirmed utilizing the sequencing of the ITS2 rDNA gene which is considered good marker in the differentiation between the digenean species and the phylogeny analysis. Histopathological examination of sampled fish tissues has revealed that EMC infection was not only limited to fish musculatures, yet it extends to internal organs including spleen and kidney to present a unique form of systemic EMC infection. EMC were documented within the splenic & renal tissues with remarkable activation of melanomacrophage centers (MMC) denoting the pathophysiological response of hematopoietic tissues to the EMC invasion. The current study sheds light on the growing danger of aquatic pollution and its direct trigger of zoonotic metacercarial spread through the consumption of infected fish flesh.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes. Current diagnostic markers (e.g., UACR, eGFR) exhibit limitations in sensitivity and specificity, underscoring the need for novel approaches.

We integrated single-cell RNA sequencing (scRNA-seq) of kidney tissues from 30 individuals (18 healthy, 12 DKD) with serum proteomics data. Cellular heterogeneity and dysregulated pathways were analyzed using Seurat and pathway enrichment analyses. Intercellular communication networks were deciphered via tensor-cell2cell. A LASSO model identified hub genes, followed by robust validation across independent bulk RNA-seq cohorts (Nephrectomy and Nephroseq). Integration with proteomics prioritized three candidate biomarkers-IGFBP2, B2M, and CST3- which were further assessed in murine DKD models (STZ/HFD-induced) and clinical serum samples (n = 139). Drug-target interactions were predicted using ChEMBL and validated by molecular docking.

(1) scRNA-seq revealed aberrant activation of immune pathways and enhanced tubule cell repair in DKD. (2) Cell-cell communication analysis identified 43 hub genes, with 8 genes showing consistent upregulation in glomerular and tubular compartments. (3) Integration of proteomics and transcriptomics pinpointed three serum biomarkers-IGFBP2, B2M, CST3. (4) Longitudinal validation in STZ-induced murine models (n = 16) and human clinical samples (n = 139) confirmed progressive, stage-dependent elevation of all three biomarkers, with late-stage DKD showing the most pronounced elevation versus controls (p < 0.001). (5) Molecular docking predicted high-affinity binding of pramlintide acetate to CST3/IGFBP2 and rivipansel to B2M.

Through a multi-omics approach, we identified IGFBP2/B2M/CST3 as a non-invasive biomarker panel for DKD progression, highlighting their roles as both diagnostic markers and therapeutic targets.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths globally, with limited treatment options and a poor prognosis. The identification of reliable prognostic biomarkers and novel therapeutic candidates is essential for improving patient outcomes. This study employed an integrative bioinformatics and molecular simulation approach to uncover key gene signatures and explore potential plant-based therapeutics for HCC. Gene expression profiles from the GEO dataset GSE121248 were analyzed using R-based statistical tools to identify differentially expressed genes (DEGs). Key hub genes were selected through protein-protein interaction network analysis and functional enrichment. Three hub genesCOL1A1, NQO1, and FOS-were identified, and their expression was validated using the TCGA, GEPIA, and HPA databases. Notably, COL1A1 and NQO1 were upregulated in tumor tissues and associated with poor survival outcomes, while FOS was downregulated. To identify therapeutic candidates, bioactive compounds from Astragalus membranaceus were screened using ADMET profiling. Selected compounds were docked with the hub proteins, and molecular dynamics simulations, MM/GBSA binding energy calculations, and quantum chemical descriptors were employed to evaluate stability and reactivity. Among the candidates, isorhamnetin demonstrated strong and stable binding to all three hub targets, suggesting its potential as a multi-target inhibitor for HCC therapy. These findings provide new insights into HCC pathogenesis and propose isorhamnetin as a promising natural compound for further experimental validation.