Mesenchymal Stem Cell-Conditioned Media Modulate HUVEC Response to H2O2: Impact on Gene Expression and Potential for Atherosclerosis Intervention.

Background: We studied the potential of human bone marrow-derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H2O2. Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory-related genes, namely, TGF-ß1, FOS, ATF3, RAF-1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H2O2, or with varying concentrations of H2O2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real-time polymerase chain reaction (RT-PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H2O2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory-related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H2O2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms.

Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury.

Background and Objective: Isoproterenol (ISO) is a non-selective ß-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of ß-receptors by ISO can cause "cardiorenal syndrome," a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury. Materials and Methods: The kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis. Results: ISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters. Conclusion: L-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.

Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury.

Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO4) while being treated with Curc or nCurc for 7 days. Cu-triggered lung oxidative stress detected as dysregulation of oxidative/antioxidant markers, a downregulation of Nrf-2/HO-1 signaling, and an increase in the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and intracellular adhesion molecule-1 (ICAM-1). Additionally, it decreased the expression of lung-specific proteins, surfactant protein-C (SP-C), and mucin-1 (MUC-1), induced apoptosis, and caused changes in lung histology. Curc and nCurc alleviated CuSO4-induced lung injury by suppressing oxidative damage and inflammation and activating Nrf-2/HO-1. They also prevented apoptosis and restored the normal expression of SP-C and MUC-1. We concluded that nCurc exhibited superior efficacy compared with Curc in mitigating CuSO4-induced lung injury. This was associated with reduced oxidative stress, inflammation, and apoptotic responses and increased Nrf2/HO-1 signaling and expression of SP-C and MUC-1.