Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. Oxidation of low-density lipoprotein (LDL) cholesterol is one of the key factors for the development of atherosclerosis. Nonoxidized LDL have a low affinity for macrophages, so they are not themselves a risk factor. However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment. In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research.

Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.

Objective: The most common multifactorial neurodegenerative disorder occurring in old age is Alzheimer’s disease. The neuropathological hallmarks of that disorder are amyloid plaques with the presence of β -amyloid aggregates, intraneuronal tau protein tangles, and chronic inflammation. Brain cells such as microglia and astrocytes are inflammatory cells associated with Alzheimer’s disease and involved in the production of inflammatory mediators, such as cytokines and chemokines. Chemokines consist of a large family of protein mediators with low molecular weight, which able to control the migration and residence of all immune cells. In pathological conditions, such as Alzheimer’s disease, chemokines contribute to the inflammatory response by recruiting T cells and controlling microglia/ macrophages activation. Methods: The present study focuses on the role that chemokines and their receptors play in Alzheimer's disease and in processes such as inflammation and oxidative stress. Results: Chemokines are important mediators in AD and inflammation. They promote Aβ deposition and TAU hyperphosphorylation aggravating and increasing the progression of AD. Moreover, they affect the processing of senile plaques and produce abnormal TAU phosphorylation. Conclusion: There is no cure for AD but the therapeutic potential of chemokines to control the development of the disease may be a field of study to consider in the future.

Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels; however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins (10⁻⁸ M), Rn (10⁻⁶ M), and Ins + Rn (10⁻⁸ M and 10⁻⁶ M, respectively) were added to astrocytes for 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. Rn increased protein expression of Cu/Zn-SOD and the pro-inflammatory protein COX-2 was upregulated by Ins. On the contrary, no significant changes were found in the protein expression of NF-κB and IκB. The presence of Rn produced an increase in p-ERK protein and a significant decrease in COX-2 protein expression. Furthermore, Rn significantly increased the effects of Ins on the expression of p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ. In addition, Rn + Ins produced a significant decrease in COX-2 expression. In conclusion, Rn facilitated the effects of insulin on the p-AKT, p-eNOS, p-ERK, Mn-SOD, and PPAR-γ signaling pathways, as well as on the anti-inflammatory and antioxidant effects of the hormone.

Insulin (Ins) regulates multiple intracellular signalling pathways involved in cell survival, oxidative stress responses, and tau phosphorylation. Dysregulation of these pathways has been implicated in neurodegenerative disorders, including Alzheimer’s disease (AD). The present study evaluated the effects of insulin on protein kinase B/glycogen synthase kinase-3 beta (AKT/GSK-3β) signalling, tau phosphorylation, and oxidative stress-related markers in SH-SY5Y neuroblastoma cells. Cell metabolic activity was assessed using the (diphenyltetrazolium bromide) MTT assay, while cell number and viability were evaluated by Trypan Blue exclusion, necrosis by lactate dehydrogenase (LDH) release, and apoptosis by Caspase-3 activity. Western blot analysis was performed to evaluate the expression of phosphorylated AKT (p-AKT), phosphorylated GSK-3β (p-GSK-3β Ser9), phosphorylated TAU (pTAU), nuclear factor erythroid 2-related factor 2 (NRF2), manganese superoxide dismutase (Mn-SOD), and copper/zinc superoxide dismutase (Cu/Zn-SOD). Lipid peroxidation was determined by measuring malondialdehyde (MDA) levels using a colorimetric/fluorometric assay. Insulin treatment increased MTT reduction (31.25%) and cell metabolic activity (119.15%) while reducing LDH release (19.2%) and Caspase-3 activity (31.26%). In addition, insulin significantly increased p-AKT (34.2%) and p-GSK-3β (Ser9) (19.9%) levels. A reduction in pTAU levels (53.39%) was also observed following insulin treatment. Furthermore, insulin increased NRF2 expression (18.77%), Cu/Zn-SOD (37.29%), and Mn-SOD (50.16%) and reduced MDA levels (13.95%). These findings indicate that insulin modulates signalling pathways associated with tau phosphorylation and cellular redox regulation in SH-SY5Y cells. Insulin treatment was associated with increased AKT and GSK-3β phosphorylation, reduced tau phosphorylation, and changes in oxidative stress-related markers in SH-SY5Y neuroblastoma cells. These findings support a role for insulin in the modulation of molecular pathways implicated in cellular stress responses and tau regulation. Further studies using differentiated neuronal models and disease-relevant conditions are required to determine the relevance of these observations to neurodegenerative disorders.