Urokinase receptors regulate the interplay between inflammation, immunity, and blood clotting. The soluble urokinase plasminogen activator system is an immunologic regulator affecting endothelial function and its related receptor; the soluble urokinase plasminogen activator receptor (suPAR) has been reported to impact kidney injury. This work aims to measure serum levels of suPAR in COVID-19 patients and correlate the measurements with variable clinicolaboratory parameters and patient outcomes. In this prospective cohort study, 150 COVID-19 patients and 50 controls were included. The circulating suPAR levels were quantified by Enzyme-linked immunosorbent assay (ELISA). Routine COVID-19 laboratory assessments, including CBC, CRP, LDH, serum creatinine, and estimated glomerular filtration rates, were performed. The need for oxygen therapy, CO-RAD score, and survival rates was assessed. Bioinformatic analysis and molecular docking were run to explore the urokinase receptor structure/function and to characterize molecules as potential anti-suPAR therapeutic targets, respectively. We found higher circulating suPAR levels in COVID-19 patients vs. controls (p < 0.001). Circulating suPAR levels positively correlated with COVID-19 severity, the need for O₂ therapy, the total leukocytes count, and the neutrophils to lymphocyte ratio, while they were negatively correlated with the O₂ saturation level, albumin, blood calcium, lymphocytic count, and GFR. In addition, the suPAR levels were associated with poor prognostic outcomes such as a high incidence of acute kidney injury (AKI) and mortality rate. Kaplan–Meier curves showed a lower survival rate with higher suPAR levels. The logistic regression analysis confirmed the significant association of suPAR levels with the occurrence of AKI related to COVID-19 and with increased mortality probability within three months of COVID-19 follow-up. Some compounds that can act similarly to uPAR were discovered and tested by molecular docking to identify the possible ligand–protein interactions. In conclusion, higher circulating suPAR levels were associated with COVID-19 severity and could be considered a putative predictor of AKI development and mortality.

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo.

Diabetic nephropathy (DN) affects about one-third of patients with diabetes and can lead to end-stage renal disease despite numerous trials aimed at improving diabetic management. Non-coding RNAs (ncRNAs) represent a new frontier in DN research, as increasing evidence suggests their involvement in the occurrence and progression of DN. A growing body of evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in DN signaling pathways might serve as novel biomarkers or therapeutic targets, although this remains to be fully explored. Our study included four groups, each comprising 40 adults: patients with diabetes (a) without albuminuria, (b) with microalbuminuria, (c) with macroalbuminuria, and a control group. All participants underwent history-taking and clinicolaboratory assessments, including CBC, fasting blood sugar, HbA1c, lipid profile, liver function, and renal function tests. Additionally, expressions of lncRNA H19, miRNA-29b, PI3K, AKT, mTOR, and HIF-1 alpha were assessed using qPCR. lncRNA H19 expression was upregulated in patients with albuminuria compared to the DM group. Furthermore, based on qPCR, the level of lncRNA H19 was negatively correlated with eGFR and miRNA-29b expression. On the other hand, the lncRNA H19 level was positively correlated with PI3K, AKT, mTOR, and HIF-1 alpha levels. We also found that the lncH19/miRNA-29b ratio was significantly increased in patients with DN and macroalbuminuria. In conclusion, lncRNA H19 was upregulated in patients with DN, and this increase was associated with miRNA29b downregulation. Therefore, our study suggests a novel link between the lncH19/miRNA-29b ratio and DN, indicating that it might serve as a potential biomarker for the dynamic monitoring of DN.

Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa , possesses potent antioxidant and anticancer properties but suffers from poor aqueous solubility and limited bioavailability. This study evaluates the therapeutic efficacy of TQ encapsulated within poly(lactic-co-glycolic acid) nanoparticles (TQ-PNPs), synthesized via solvent evaporation and physicochemically characterized by dynamic light scattering, zeta potential measurement, and transmission electron microscopy. 90 female Swiss albino mice were allocated to 6 groups: control, TQ, TQ-PNPs (10 mg/kg, oral), EAC, EAC + TQ, and EAC + TQ-PNPs. Endpoints included tumor viability, hematological and biochemical indices, antioxidant enzyme activity, pro-inflammatory cytokines, oxidative stress biomarkers, and hepatorenal histopathology. Molecular docking assessed TQ binding affinities toward key antioxidant enzymes. Compared to free TQ, TQ-PNPs was associated with significantly greater reductions in tumor burden, inflammatory cytokines (IL-2, IL-6, TNF-α), and oxidative stress markers, with concurrent restoration of antioxidant defenses and enhanced hepatorenal protection. Molecular docking indicated high-affinity interactions between TQ and catalase, superoxide dismutase, and glutathione peroxidase, supporting a plausible mechanistic basis for its antioxidative activity but requiring experimental confirmation. These findings suggest that PLGA-based nanoencapsulation can enhance TQ’s bioavailability and therapeutic index in this murine EAC model, positioning TQ-PNPs as a promising platform for phytochemical delivery in cancer management.

Arsenic (As) is a toxic trace element with neurodevelopmental, carcinogenic, and other adverse effects. Meanwhile, selenium (Se) is an antioxidant trace element with essential physiological roles in humans. The preterm neonate is the most heavily transfused patient. The multiple blood transfusions could expose this vulnerable group to trace elements with variable effects. This study aimed to quantify As and Se in various blood products that were used in neonatal blood transfusions alongside an estimate of a dose per transfusion. In addition to exposure quantification, database mining and molecular docking analysis were performed to explore potential detoxification strategies. Samples from transfusion bags: N = 120; 30 samples of each type of blood product (plasma, platelets, packed RBCs (pRBCs), and whole blood “WB”) were analyzed for As and Se by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The As and Se medians of all blood units were 0.6 and 74 μg/L, respectively. About 20% of donors have As levels above 1 μg/L. In addition, 74% of donors have Se levels less than 100 μg/L (the level of sub-optimal activity of the antioxidant enzyme glutathione peroxidase), and 60% of the donors have Se levels below the accepted minimum Se level (80 μg/L). The pRBCs were the units with the highest As and Se content. Meanwhile, WBs were the units with the highest dose per transfusion. Key methyl donors—folic acid, S-adenosylmethionine (SAM), and glutathione (GSH)—showed strong binding affinity to the active site of arsenite methyltransferase (AS3MT), a crucial enzyme in As metabolism. These ligands interacted with conserved catalytic residues such as ASN173, ASP115, and CYS92, suggesting a supportive role in enhancing As methylation and clearance. The present study highlights that neonates are exposed to As and Se via different blood product transfusions with high potential to increase As and decrease Se after transfusion. It is recommended to select donors and screen blood units with optimal Se levels and minimal As content for neonatal transfusions. The integration of in silico docking with exposure assessment adds mechanistic insight and highlights the potential for targeted nutritional interventions to reduce As toxicity in vulnerable neonatal populations.

Background: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which cytotoxic T cells contribute to tissue damage through dysregulated effector pathways. CD107a (LAMP-1) serves as a functional marker of CD8⁺ T-cell degranulation and may reflect disease-related alterations in cytotoxicity. Objective: To investigate the expression of CD107a on cytotoxic T cells in SLE patients and evaluate its relationship with disease activity and immunological features. Methods: Demographic, hematological, and immunological profiles of SLE patients and controls were compared. Flow cytometry was used to evaluate CD3⁺, CD3⁺CD8⁺, CD4⁺, double-negative T cells, and CD107a⁺CD8⁺ subsets. Correlations with disease activity and diagnostic performance were assessed. Results: SLE patients showed anemia, thrombocytopenia, and lymphopenia compared with controls. Immunophenotyping revealed significantly elevated CD3⁺CD8⁺, CD107a⁺CD8⁺ T cells in SLE, and reduced CD4⁺ counts. While CD107a⁺CD8⁺ levels were strongly elevated, they did not correlate with disease activity scores, suggesting persistent upregulation of CD107a expression independent of clinical severity. ROC curve analysis indicated that CD3⁺ and CD3⁺CD8⁺ subsets had diagnostic utility, while double-negative T cells showed additional value. Conclusion: SLE is associated with increased CD107a⁺CD8⁺ T cells, reflecting heightened basal expression of this degranulation marker regardless of disease activity level. These findings underscore the role of altered cytotoxic T-cell function in SLE immunopathogenesis and support CD107a as a potential biomarker of immune dysregulation.