Hepatotoxic contaminants such as zearalenone (ZEA) are widely present in foods. Marine algae have a wide range of potential applications in pharmaceuticals, cosmetics, and food products. Research is ongoing to develop treatments and products based on the compounds found in algae. Fucoxanthin (FXN) is a brown-algae-derived dietary compound that is reported to prevent hepatotoxicity caused by ZEA. This compound has multiple biological functions, including anti-diabetic, anti-obesity, anti-microbial, and anti-cancer properties. Furthermore, FXN is a powerful antioxidant. In this study, we examined the effects of FXN on ZEA-induced stress and inflammation in HepG2 cells. MTT assays, ROS generation assays, Western blots, and apoptosis analysis were used to evaluate the effects of FXN on ZEA-induced HepG2 cell inflammation. Pre-incubation with FXN reduced the cytotoxicity of ZEA toward HepG2 cells. FXN inhibited the ZEA-induced production of pro-inflammatory cytokines, including IL-1 β, IL-6, and TNF-α. Moreover, FXN increased HO-1 expression in HepG2 by activating the PI3K/AKT/NRF2 signaling pathway. In conclusion, FXN inhibits ZEA-induced inflammation and oxidative stress in hepatocytes by targeting Nrf2 via activating PI3K/AKT signaling.

Schizophrenia (SZ), a complex and chronic neuropsychiatric disorder affecting approximately 1 % of the general population, presents diagnostic challenges due to the absence of reliable biomarkers, and relying mainly on clinical observations. MicroRNAs (miRNAs) signatures in a wide range of diseases, including psychiatric disorders, hold immense potential for serving as biomarkers. This study aimed to analyze the expression levels of specific microRNAs (miRNAs) namely miR-29b-3p, miR-106b-5p, and miR-199a-3p and explore their diagnostic potential for SZ in Jordanian patients. Small RNAs (miRNAs) were extracted from plasma samples of 30 SZ patients and 35 healthy controls. RNA was reverse transcribed and quantified by real-time polymerase chain reaction (qRT-PCR). The expression levels of three miRNAs (miR-29b-3p, miR-106b-5p and miR-199a-3p) were analyzed. Receiver operating characteristic (ROC) curves analysis was performed to evaluate diagnostic value of these miRNAs. Target genes prediction, functional enrichment and pathway analyses were done using miRWalk and Metascape. STRING database was used to construct protein-protein network and identify hub genes. Notably, miR-106b-5p and miR-199a-3p were significantly upregulated (p < 0.0001), while miRNA-29b-3p was downregulated (p < 0.0001) in SZ patients compared to controls. The diagnostic potential was assessed through ROC curves, revealing substantial diagnostic value for miR-199a-3p (AUC: 0.979) followed by miR-106b-5p (AUC: 0.774), with limited diagnostic efficacy for miR-29b-3p. Additionally, bioinformatic analyses for the predicted target genes of the diagnostically significant miRNAs uncovered Gene Ontology (GO) terms related to neurological development, including morphogenesis, which is involved in neuron differentiation, brain development, head development, and neuron projection morphogenesis. These findings highlight a potential connection between the identified miRNAs and SZ pathophysiology in the studied Jordanian population. Furthermore, a protein-protein interaction network from the target genes identified in association with neurological development in the Gene Ontology (GO) terms deepens our comprehension of the molecular landscape of the regulated target genes. This comprehensive exploration highlights the promising role of miRNAs in unraveling intricate molecular pathways associated with SZ in the Jordanian cohort and suggests that plasma miRNAs could serve as reliable biomarkers for SZ diagnosis and disease progression. Remarkably, this study represents the first investigation into the role of circulating miRNA expression among Jordanian patients with SZ, providing valuable insights into the diagnostic landscape of this disorder.

Cell cycle regulatory proteins plays a pivotal role in the development and progression of many human malignancies. Identification of their biological functions as well as their prognostic utility presents an active field of research. As a continuation of the ongoing efforts to elucidate the molecular characteristics of clear cell renal cell carcinoma (ccRCC); we present a comprehensive bioinformatics study targeting the prognostic and mechanistic role of cyclin-dependent kinase inhibitor 3 (CDKN3) in ccRCC. The ccRCC cohort from the Cancer Genome Atlas Program was accessed through the UCSC Xena browser to obtain CDKN3 mRNA expression data and their corresponding clinicopathological variables. The independent prognostic signature of CDKN3 was evaluated using univariate and multivariate Cox logistic regression analysis. Gene set enrichment analysis and co-expression gene functional annotations were used to discern CDKN3-related altered molecular pathways. The tumor immune microenvironment was evaluated using TIMER 2.0 and gene expression profiling interactive analysis. CDKN3 upregulation is associated with shortened overall survival (hazard ratio [HR] = 2.325, 95% confident interval [CI]: 1.703–3.173, P < .0001) in the Cancer Genome Atlas Program ccRCC cohort. Univariate (HR: 0.426, 95% CI: 0.316–0.576, P < .001) and multivariate (HR: 0.560, 95% CI: 0.409–0.766, P < .001) Cox logistic regression analyses indicate that CDKN3 is an independent prognostic variable of the overall survival. High CDKN3 expression is associated with enrichment within the following pathways including allograph rejection, epithelial–mesenchymal transition, mitotic spindle, inflammatory response, IL-6/JAK/STAT3 signaling, spermatogenesis, TNF-α signaling via NF-kB pathway, complement activation, KRAS signaling, and INF-γ signaling. CDKN3 is also associated with significant infiltration of a wide spectrum of immune cells and correlates remarkably with immune-related genes. CDKN3 is a poor prognostic biomarker in ccRCC that alters many molecular pathways and impacts the tumor immune microenvironment.

Androgens play a biological role in breast cancer, including triple-negative breast cancer (TNBC). Treatment of TNBC cells with dihydrotestosterone (DHT) induces their mesenchymal transition, migration, and invasion. Cathepsin B, a perinuclear lysosomal protease that relocates to the periphery of invasive cancer cells and is over-secreted, was hypothesized herein to mediate androgen-induced migration and invasion of TNBC cells. Initially, bioinformatics analysis revealed associations between tissue cathepsin B expression and breast cancer, particularly TNBC, as well as androgen receptor (AR) expression. DHT induced the peripheral distribution and extracellular release of cathepsin B specifically in AR-positive TNBC cells (MDA-MB-453 and BT549). Cathepsin B inhibition completely blocked DHT-induced migration and invasion of BT549 cells, but only partially in MDA-MB-453 cells. AR inhibition also partially reduced the DHT-induced release of cathepsin B in MDA-MB-453 cells but had no effect on BT549 cells. Membrane-impermeable testosterone (T-BSA) increased cathepsin B release and its peripheral intracellular distribution in both cell lines. T-BSA also promoted their migration and invasion, but only the migration of MDA-MB-453 cells depended on cathepsin B. Short-term treatment with either DHT or T-BSA distributed cathepsin B peripherally, suggesting rapid, non-genomic signaling. Whereas T-BSA induced rapid cathepsin B release from MDA-MB-453 cells, DHT caused a delayed response. Inhibition of the MAPK, PI3K, and β-catenin signaling pathways suggested their cell line-specific involvement. Collectively, these results suggest that DHT regulates cathepsin B in TNBC cells via distinct rapid, non-genomic mechanisms involving intracellular and membrane AR in a cell-selective manner.

Endomucin (EMCN) contributes to both cell adhesion and signaling processes, thereby participating in the modulation of immune responses within the vasculature. In this study, we uncover how EMCN modulates the tumor immune microenvironment in clear-cell renal cell carcinoma (ccRCC). The Cancer Genome Atlas (TCGA) was used to obtain clinicopathological and expression data on KIRC. The prognostic significance of EMCN expression in ccRCC was assessed through univariate analysis. DNMIVD was used to investigate the methylation status of EMCN in tumor and normal adjacent tissue (NAT). TCGExplorer was utilized to employ GSEA to identify pathways enriched by the high or low expression of EMCN. Hallmark Gene sets from MSigDB were utilized. The immune microenvironment was evaluated using the Tumor IMmune Estimation Resource (TIMER 2.0). High EMCN expression was associated with heightened overall survival and better survival (HR: 0.60, 95% CI: 0.52–0.68, p < 0.0001) in the TCGA ccRCC cohort. The promoter region of EMCN was hypermethylated in tumor tissue, in contrast to normal adjacent tissue, with an increased beta value of 0.13715 (p < 0.001) associated with decreased expression of EMCN in tumor tissue compared to NAT. The top three enriched GSEA terms when EMCN was highly expressed were hallmark_TGF_beta_signaling, KRAS_signalling_up, and Apical_junction. In contrast, when the expression of EMCN was low, E2F_targets, Oxidative_phosphorylation, and MYC_targets_v2 were the top terms. EMCN expression was positively correlated with resting memory CD4+T cells (ρ = 0.217, p = 2.68e⁻⁶), naïve B cells (ρ = 0.273, p = 2.43e⁻⁹), plasma B cells (ρ = 0.158, p = 6.73e⁻⁴), M1 macrophages (ρ = 0.167, p = 3.05e⁻⁴), Monocytes (ρ = 0.29, p = 2.17e⁻¹⁰), resting NK cells (ρ = 0.208, p = 6.39e⁻⁶), activated mast cells (ρ = 0.373, p = 1.05e⁻¹⁶), and M2 macrophages (ρ = 0.127, p = 6.45e⁻³). It correlated negatively with Tregs (ρ = −0.349, p = 1.23e⁻¹⁴), activated memory CD4+ T cells (ρ = −0.17, p = 2.42e⁻⁴), follicular helper T cells (ρ = −0.209, p = 6.20e⁻⁶), neutrophils (ρ = −0.101, p = 3.07e⁻²), M0 macrophages (ρ = −0.333, p = 2.15e⁻¹³), and memory B cells (ρ = −0.217, p = 2.53e⁻⁶).