Palmitic Acid Modulates Microglial Cell Response to Metabolic Endotoxemia in an In Vitro Study.

Metabolic endotoxemia (ME) is characterized by a 2-3-fold increase in blood endotoxin levels and low-grade systemic inflammation without apparent infection. ME is usually accompanied by metabolic syndrome, characterized by central obesity and hyperlipidemia. According to numerous studies, ME may lead to functional brain disorders, including cognitive decline, depression, and dementia. In the current in vitro study, we aimed to determine the direct and indirect impact of endotoxin (LPS) and palmitic acid (PA), representing saturated fatty acids, on the inflammatory and oxidative stress response in the human microglial HMC3 cells unstimulated and stimulated with IFNγ. The study's results revealed that direct HMC3 cell exposition to endotoxin and PA increased inflammatory response measured as levels of IL-6 and MCP-1 released into the medium and PGE2 levels in cell lysates. Moreover, direct HMC3 cell treatment with PA and LPS induced oxidative stress, i.e., ROS and COX-2 production and lipid peroxidation. On the contrary, an indirect effect of LPS and PA on microglial cells, assessed as the impact of macrophage metabolites, was much lower regarding the inflammatory response, although still associated with oxidative stress. Interestingly, IFNγ had a protective effect on microglial cells, reducing the production of pro-inflammatory mediators and oxidative stress in HMC3 cells treated directly and indirectly with LPS and PA.

The Role of Palmitic Acid in the Co-Toxicity of Bacterial Metabolites to Endothelial Cells.

Introduction: Metabolic endotoxemia most often results from obesity and is accompanied by an increase in the permeability of the intestinal epithelial barrier, allowing co-absorption of bacterial metabolites and diet-derived fatty acids into the bloodstream. A high-fat diet (HFD) leading to obesity is a significant extrinsic factor in developing vascular atherosclerosis. In this study, we evaluated the effects of palmitic acid (PA) as a representative of long-chain saturated fatty acids (LCSFA) commonly present in HFDs, along with endotoxin (LPS; lipopolysaccharide) and uremic toxin indoxyl sulfate (IS), on human vascular endothelial cells (HUVECs). Methods: HUVECs viability was measured based on tetrazolium salt metabolism, and cell morphology was assessed with fluorescein-phalloidin staining of cells' actin cytoskeleton. The effects of simultaneous treatment of endothelial cells with PA, LPS, and IS on nitro-oxidative stress in vascular cells were evaluated quantitatively with fluorescent probes. The expression of vascular cell adhesion molecule VCAM-1, E-selectin, and occludin, an essential tight junction protein, in HUVECs treated with these metabolites was evaluated in Western blot. Results: PA, combined with LPS and IS, did not influence HUVECs viability but induced stress on actin fibers and focal adhesion complexes. Moreover, PA combined with LPS significantly enhanced reactive oxygen species (ROS) production in HUVECs but decreased nitric oxide (NO) generation. PA also considerably increased the expression of VCAM-1 and E-selectin in HUVECs treated with LPS or IS but decreased occludin expression. Conclusion: Palmitic acid enhances the toxic effect of metabolic endotoxemia on the vascular endothelium.

Production, Mechanical Properties and Biomedical Characterization of ZrTi-Based Bulk Metallic Glasses in Comparison with 316L Stainless Steel and Ti6Al4V Alloy.

Microstructure, mechanical properties, corrosion resistance, and biocompatibility were studied for rapidly cooled 3 mm rods of Zr40Ti15Cu10Ni10Be25, Zr50Ti5Cu10Ni10Be25, and Zr40Ti15Cu10Ni5Si5Be25 (at.%) alloys, as well as for the reference 316L stainless steel and Ti-based Ti6Al4V alloy. Microstructure investigations confirm that Zr-based bulk metallic samples exhibit a glassy structure with minor fractions of crystalline phases. The nanoindentation tests carried out for all investigated composite materials allowed us to determine the mechanical parameters of individual phases observed in the samples. The instrumental hardness and elastic to total deformation energy ratio for every single phase observed in the manufactured Zr-based materials are higher than for the reference materials (316L stainless steel and Ti6Al4V alloy). A scratch tester used to determine the wear behavior of manufactured samples and reference materials revealed the effect of microstructure on mechanical parameters such as residual depth, friction force, and coefficient of friction. Electrochemical investigations in simulated body fluid performed up to 120 h show better or comparable corrosion resistance of Zr-based bulk metallic glasses in comparison with 316L stainless steel and Ti6Al4V alloy. The fibroblasts viability studies confirm the good biocompatibility of the produced materials. All obtained results show that fabricated biocompatible Zr-based materials are promising candidates for biomedical implants that require enhanced mechanical properties.