Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model.

The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson's disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic ß-sitosterol ß-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.

Effects of Propolis on Infectious Diseases of Medical Relevance.

Infectious diseases are a significant problem affecting the public health and economic stability of societies all over the world. Treatment is available for most of these diseases; however, many pathogens have developed resistance to drugs, necessitating the development of new therapies with chemical agents, which can have serious side effects and high toxicity. In addition, the severity and aggressiveness of emerging and re-emerging diseases, such as pandemics caused by viral agents, have led to the priority of investigating new therapies to complement the treatment of different infectious diseases. Alternative and complementary medicine is widely used throughout the world due to its low cost and easy access and has been shown to provide a wide repertoire of options for the treatment of various conditions. In this work, we address the relevance of the effects of propolis on the causal pathogens of the main infectious diseases with medical relevance; the existing compiled information shows that propolis has effects on Gram-positive and Gram-negative bacteria, fungi, protozoan parasites and helminths, and viruses; however, challenges remain, such as the assessment of their effects in clinical studies for adequate and safe use.

Biomedical Properties of Propolis on Diverse Chronic Diseases and Its Potential Applications and Health Benefits.

The use of alternative medicine products has increased tremendously in recent decades and it is estimated that approximately 80% of patients globally depend on them for some part of their primary health care. Propolis is a beekeeping product widely used in alternative medicine. It is a natural resinous product that bees collect from various plants and mix with beeswax and salivary enzymes and comprises a complex mixture of compounds. Various biomedical properties of propolis have been studied and reported in infectious and non-infectious diseases. However, the pharmacological activity and chemical composition of propolis is highly variable depending on its geographical origin, so it is important to describe and study the biomedical properties of propolis from different geographic regions. A number of chronic diseases, such as diabetes, obesity, and cancer, are the leading causes of global mortality, generating significant economic losses in many countries. In this review, we focus on compiling relevant information about propolis research related to diabetes, obesity, and cancer. The study of propolis could generate both new and accessible alternatives for the treatment of various diseases and will help to effectively evaluate the safety of its use.

Hypohidrotic ectodermal dysplasia: clinical and molecular review.

Hypohidrotic Ectodermal Dysplasia (HED) is a genetic human disorder which affects structures of ectodermal origin. Although there are autosomal recessive and dominant forms, X-linked (XL) is the most frequent form of the disease. This XL-HED phenotype is associated with mutations in the gene encoding the transmembrane protein ectodysplasin-1 (EDA1), a member of the TNFα-related signaling pathway. The proteins from this pathway are involved in signal transduction from ectoderm to mesenchyme leading to the development of ectoderm-derived structures in the fetus such as hair, teeth, skin, nails, and eccrine sweat glands. The aim of this review was to update the main clinical characteristics of HED regarding to recent molecular advances in the comprehension of all the possible genes involved in this group of disorders since it is known that Eda-A1-Edar signaling has multiple roles in ectodermal organ development, regulating their initiation, morphogenesis, and differentiation steps. The knowledge of the biological mechanisms that generate HED is needed for both a better detection of possible cases and for the design of efficient prevention and treatment approaches.

Increased expression of inflammation-related co-stimulatory molecules by HUVECs from newborns with a strong family history of myocardial infarction stimulated with TNF-alpha and oxLDL.

BACKGROUND: Recent findings indicate that atherosclerosis, a chronic inflammatory process, might start during childhood. Nevertheless, the expression of inflammation-related molecules of endothelial cell isolated from healthy neonates with a strong family history of myocardial infarction (SFHMI) has been rarely analyzed. METHODS: Human umbilical vein endothelial cells (HUVECs) from children with SFHMI were assessed for the expression of CD40 and CD40L, in the presence of TNF-alpha and oxLDL. The intracellular content of CD80, CXCL8 and tissue factor by HUVECs stimulated with a CD40 agonist monoclonal antibody as well as monocytes/lymphocyte adhesion to TNF-alpha-stimulated HUVECs was also evaluated. RESULTS: The basal expression of CD40 and CD40L was higher in SFHMI-positive HUVECs in comparison to controls. TNF-alpha and oxLDL upregulated the expression of CD40 and CD40L in SFHMI versus control HUVECs (p<0.001). The intracellular expression of CXCL8, tissue factor and CD80 was also higher than in controls, and the adhesion of lymphocyte- and monocyte-like cells augmented upon TNF-alpha stimulation. CONCLUSIONS: It is possible that the modifications observed in the SFHMI-positive HUVECs, all of them relevant to the atherosclerosis process, may lead to early inflammatory reactions, thus contributing to the premature initiation of atherosclerotic lesions in these children.