PPARγ and cognitive performance

Recent findings have led to the discovery of many signaling pathways that link nuclear receptors with human conditions, including mental decline and neurodegenerative diseases. PPARγ agonists have been indicated as neuroprotective agents, supporting synaptic plasticity and neurite outgrowth. For these reasons, many PPARγ ligands have been proposed for the improvement of cognitive performance in different pathological conditions. In this review, the research on this issue is extensively discussed

Food habits, Life style, Genetic background in tumour initiation and progression of Reproductive system

The relationship between diet and health is really engaging, it has been showed that modifications in dietary intake and the benefits of the Mediterranean diet, can importantly increase life expectancy, reducing the risk of chronic disease and improve quality of life. In this way, several studies assigned a highest reduction in tumor incidence to monosaturated and saturated lipids present in vegetables, such olive oil. On these basis, this study will be focused on the comprehension and understanding of initiation and progression phases linked to environmental stressors and food habits in the tumours of the reproductive system (breast and ovarian cancer). Recently it has been described the potential effect of the olive tree (Olea europaea) leaves, oil and fruits to inhibit proliferation and to induce apoptosis in different cancer cell lines. The phenolic fraction of Olive extract becomes specially interesting, including a polyphenol called Oleuropein (OL) present at higher levels in olives and leaves- as well as its hydrolysis metabolite, Hydroxytyrosol (HT). Taking this background into account, we have focused our research in the analysis of Olive leaf extracts with a high content in OL (48%) as a potential cell viability reducing agent on a malignant triple negative breast cancer cell line, MDA-MB- 231, which is highly aggressive. On this model, cell viability was measured with a MTS assay 24 and 48 h after the treatment with the Olive extract. The preliminary results seem to indicate that this extract at high concentrations (200-400µg/mL) determines a reduction in the MDA- MB-231 cell viability

Lifestyle and food habits impact on chronic diseases: Roles of PPARs

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert important functions in mediating the pleiotropic effects of diverse exogenous factors such as physical exercise and food components. Particularly, PPARs act as transcription factors that control the expression of genes implicated in lipid and glucose metabolism, and cellular proliferation and differentiation. In this review, we aim to summarize the recent advancements reported on the effects of lifestyle and food habits on PPAR transcriptional activity in chronic disease

PPARs and energy metabolism adaptation during neurogenesis and neuronal maturation

Peroxisome proliferator activated receptors (PPARs) are a class of ligand-activated transcription factors, belonging to the superfamily of receptors for steroid and thyroid hormones, retinoids, and vitamin D. PPARs control the expression of several genes connected with carbohydrate and lipid metabolism, and it has been demonstrated that PPARs play important roles in determining neural stem cell (NSC) fate. Lipogenesis and aerobic glycolysis support the rapid proliferation during neurogenesis, and specific roles for PPARs in the control of different phases of neurogenesis have been demonstrated. Understanding the changes in metabolism during neuronal differentiation is important in the context of stem cell research, neurodegenerative diseases, and regenerative medicine. In this review, we will discuss pivotal evidence that supports the role of PPARs in energy metabolism alterations during neuronal maturation and neurodegenerative disorders

The Role of Stiffness in Cell Reprogramming: A Potential Role for Biomaterials in Inducing Tissue Regeneration

The mechanotransduction is the process by which cells sense mechanical stimuli such as elasticity, viscosity, and nanotopography of extracellular matrix and translate them into biochemical signals. The mechanotransduction regulates several aspects of the cell behavior, including migration, proliferation, and differentiation in a time-dependent manner. Several reports have indicated that cell behavior and fate are not transmitted by a single signal, but rather by an intricate network of many signals operating on different length and timescales that determine cell fate. Since cell biology and biomaterial technology are fundamentals in cell-based regenerative therapies, comprehending the interaction between cells and biomaterials may allow the design of new biomaterials for clinical therapeutic applications in tissue regeneration. In this work, we present the most relevant mechanism by which the biomechanical properties of extracellular matrix (ECM) influence cell reprogramming, with particular attention on the new technologies and materials engineering, in which are taken into account not only the biochemical and biophysical signals patterns but also the factor time

Neuronal cells rearrangement during aging and neurodegenerative disease: Metabolism, oxidative stress and organelles dynamic

Brain cells normally respond adaptively to oxidative stress or bioenergetic challenges, resulting from ongoing activity in neuronal circuits. During aging and in neurodegenerative disorders, these mechanisms are compromised. In fact, neurons show unique age-related changes in functions and metabolism, resulting in greater susceptibility to insults and disease. Aging affects the nervous system as well as other organs. More precisely, as the nervous system ages, neuron metabolism may change, inducing glucose hypometabolism, impaired transport of critical substrates underlying metabolism, alterations in calcium signaling, and mitochondrial dysfunction. Moreover, in neuronal aging, an accumulation of impaired and aggregated proteins in the cytoplasm and in mitochondria is observed, as the result of oxidative stress: reduced antioxidant defenses and/or increase of reactive oxygen species (ROS). These changes lead to greater vulnerability of neurons in various regions of the brain and increased susceptibility to several diseases. Specifically, the first part of the review article will focus on the major neuronal cells’ rearrangements during aging in response to changes in metabolism and oxidative stress, while the second part will cover the neurodegenerative disease areas in detail

Ppars In Neurodegenerative And Neuroinflammatory Pathways

PPARs are lipid sensors activate by dietary lipids or their metabolites, mainly fatty acids and eicosanoids , that play critical roles in CNS biology, since brain has a very high lipid content and has the higher energetic metabolism in the body. In neurodegenerative diseases in addition to metabolic impariment also neuroinflammation is observed and PPARs are also closely linked to inflammatory process. Several studies have revealed a complicated relationship between the innate immune response and tissue metabolism. In the brain, during pathological conditions, an alteration in metabolic status occurs, particularly involving glucose utilization and production, a condition which is generally related to metabolic changes. Taking into account the high expression of PPARs in the brain, this review will focus on the role of these transcription factors in CNS diseases

Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics

Glioblastoma (GB) is the most representative form of primary malignant brain tumour. Several studies indicated a pleiotropic role of CXCL8 in cancer due to its ability to modulate the tumour microenvironment, growth and aggressiveness of tumour cell. Previous studies indicated that CXCL8 by its receptors (CXCR1 and CXCR2) induced activation of the PI3K/p-Akt pathway, a crucial event in the regulation of cytoskeleton rearrangement and cell mobilization. Human GB primary cell culture and U-87MG cell line were used to study the effects of CXCR1 and CXCR2 blockage, by a dual allosteric antagonist, on cell migration and cytoskeletal dynamics. The data obtained point towards a specific effect of autocrine CXCL8 signalling on GB cell invasiveness by the activation of pathways involved in cell migration and cytoskeletal dynamics, such as PI3K/p-Akt/p-FAK, p-cortactin, RhoA, Cdc42, Acetylated α-tubulin and MMP2. All the data obtained support the concept that autocrine CXCL8 signalling plays a key role in the activation of an aggressive phenotype in primary glioblastoma cells and U-87MG cell line. These results provide new insights about the potential of a pharmacological approach targeting CXCR1/CXCR2 pathways to decrease migration and invasion of GB cells in the brain parenchyma, one of the principal mechanisms of recurrence

Mesalazine treatment in organotypic culture of celiac patients: Comparative study with gluten free diet

Given the central role of gluten in the pathogenesis of celiac disease (CD), a strict gluten-free diet (GFD) is the only validated treatment able to restore epithelium integrity and eliminate risks of complications. The risk of gluten contamination and the persistence of inflammation, even in patients strictly adhering to GFD, may render this treatment not always effective claiming the necessity of different new solutions. Oxidative and nitrosative stress have been indicated to play a pathophysiological role in CD. Mesalazine (5-ASA), a drug largely used in inflammatory bowel disease, has potent antinflammatory and antioxidant effects. In fact, mesalazine has been shown to decrease in vitro gluten induced cytokine response and it has been used in vivo in some refractory condition. However, its effect has never compared to that of GFD. The present study aimed to address this issue by comparing the ability of mesalazine and GFD in treating gluten-induced inflammation and oxidative stress. These effects were studied on duodenal mucosa biopsy cultures from newly diagnosed CD patients, treated or not in vitro with mesalazine, and CD biopsy cultures from patients on gluten-free diet for at least one year; and a cohort of controls constituted by healty subjects. On these models, the antioxidant cellular defences, the PPARγ, NF-kB and NOS2 proteins levels were studied. This study shows that mesalazine is as effective as GFD in reducing oxidative burst and inducing PPARγ expression; moreover it resulted more effective than GFD in decreasing NF-kB and NOS2 to the levels of controls. This article is protected by copyright. All rights reserved