Protocatechuic acid (PCA) is the major metabolite of the anthocyanin known as cyanidin 3-glucoside. It is found in plasma and tissues, such as the brain, heart, liver, and kidneys, following ...consumption of a rich source of this flavonoid. The abnormal pathological assembly of amyloid-β (Aβ) and α-synuclein (αS) is an underlying mechanism involved in the formation of amyloid plaques and Lewy bodies in the brain, which are responsible for neuropathology symptoms in Alzheimer’s (AD) and Parkinson’s diseases (PD), respectively. This research was performed to evaluate the protective effects of PCA, by establishing its potential role in inhibiting aggregation and fibril destabilization of Aβ and αS proteins. It has been found that PCA inhibits the aggregation of Aβ and αS and destabilizes their preformed fibrils. These results were confirmed by TEM images, electrophoresis, and immunoblotting experiments. Furthermore, PCA prevents the death of PC12 cells triggered by Aβ- and αS-induced toxicity.
Anoikis (or cell-detachment-induced apoptosis) is a self-defense strategy that organisms use to eliminate 'misplaced' cells, i.e. cells that are in an inappropriate location. Occasionally, detached ...or misplaced cells can overcome anoikis and survive for a certain period of time in the absence of the correct signals from the extracellular matrix (ECM). If cells are able to adapt to their new environment, then they have probably become anchorage-independent, which is one of the hallmarks of cancer cells. Anoikis resistance and anchorage-independency allow tumor cells to expand and invade adjacent tissues, and to disseminate through the body, giving rise to metastasis. Thus, overcoming anoikis is a crucial step in a series of changes that a tumor cell undergoes during malignant transformation. Tumor cells have developed a variety of strategies to bypass or overcome anoikis. Some strategies consist of adaptive cellular changes that allow the cells to behave as they would in the correct environment, so that induction of anoikis is aborted. Other strategies aim to counteract the negative effects of anoikis induction by hyperactivating survival and proliferative cascades. The recently discovered processes of autophagy and entosis also highlight the contribution of these mechanisms to rendering the cells in a dormant state until they receive a signal initiated at the ECM, thereby circumventing anoikis. In all situations, the final outcome is the ability of the tumor to grow and metastasize. A better understanding of the mechanisms underlying anoikis resistance could help to counteract tumor progression and prevent metastasis formation.
The installation of CCTV cameras in the historic centre of Malaga in March 2007 was the main crime prevention initiative implemented in the city during the past few years. This was one of the first ...multi-camera CCTV installations on streets in Spain, which is why a proper evaluation of its effectiveness is so important for the future use of such cameras. Using a quasi-experimental design with a pre/post test, we collected data from interviews with CCTV operators, police officers and local authority officials and from surveys of pedestrians and shopkeepers. The team also examined police crime data and CCTV incident data. In this paper we will discuss the results in terms of the following three hypotheses relating to crime reduction, displacement and public security: (a) the use of cameras reduces the levels of crime, whether property crime (robberies and burglaries), crimes against people or both; (b) some of those crimes are displaced to nearby areas within or close to the city centre where there is no camera coverage but where there are similar opportunities to commit crimes; and (c) people claim to feel safer in the city centre after dark after the cameras were introduced.
Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson's disease among others. The hallmark of brain neuroinflammation is the ...activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease. For this reason, novel therapeutic strategies which aim to modify the microglia polarization are being developed. Additionally, the understanding of how nutrition may influence the prevention and/or treatment of neurodegenerative diseases has grown greatly in recent years. The protective role of Mediterranean diet (MD) in preventing neurodegenerative diseases has been reported in a number of studies. The Mediterranean dietary pattern includes as distinctive features the moderate intake of red wine and extra virgin olive oil, both of them rich in polyphenolic compounds, such as resveratrol, oleuropein and hydroxytyrosol and their derivatives, which have demonstrated anti-inflammatory effects on microglia on
studies. This review summarizes our understanding of the role of dietary phenolic compounds characteristic of the MD in mitigating microglia-mediated neuroinflammation, including explanation regarding their bioavailability, metabolism and blood-brain barrier.
•Chemical hazards in grapes and wine are impacted by climate change.•Climate change produce wines with higher pH, nitrogen compounds and alcohol degree.•The most concerning: Mycotoxins, ethyl ...carbamate, SO2, proteins and biogenic amines.•Technological solutions to avoid excess of these compounds are future challenges.
Climate change has an impact on the chemical risks associated to wine consumption related with grape development and microbial contamination. We can classify chemical hazards in wine into two groups: those present in grapes due to agricultural practices, environmental contamination or fungal growth and those coming from fermentation and the winemaking process. The first group includes mycotoxins, whilst the second encompasses ethyl carbamate, biogenic amines, sulfur dioxide and proteins used as technological ingredients such as fining material. Usually the effective control of chemical hazards is achieved by assuring that they either are minimized or absent in the final product since their removal is somewhat difficult and sometimes it may affect sensory properties, which is a major issue in wine. Interestingly, it is possible to give recommendations to avoid excess of these compounds, but more research is needed to face future challenges related to climate change and consumer demands.
During alcoholic fermentation, Saccharomyces cerevisiae synthesizes different compounds, which are crucial for product quality: volatile compounds with sensory impact, and bioactive compounds such as ...melatonin (MEL) and hydroxytyrosol (HT), linked to health benefits. As many of these compounds are related with yeast's nitrogen metabolism, their production have been studied in four different commercial strains with different nitrogen requirement (Red Fruit, Uvaferm VRB, Lalvin Rhone 2323 and Lalvin QA23) being, Uvaferm UVR the higher nitrogen demander strain. All strains produced the secondary metabolites, notably Uvaferm UVR produced the highest HT concentration, despite its low growth. Uvaferm UVR emerged also as a significant producer of MEL, indicating a potential role in fermentation related stress. Moreover, Uvaferm UVR shows the highest total concentrations of volatile compounds. Multivariate analysis revealed distinct clustering based on nitrogen requirements of the strains, highlighting the strain-dependent metabolic responses.
•Uvaferm is the yeast with the highest nitrogen requirement.•The yeast with the highest HT and MEL production is Uvaferm VRB.•The most volatile compounds producer correspond to the Uvaferm VRB strain.•There is no direct relation between compounds production and the biomass produced.
Preventing the abnormal assembly of α-synuclein (α-Syn) and the correct modulation of vitagenes system exercise strong neuroprotective effects. It has been reported that melatonin (MEL), ...protocatechuic acid (PCA) and hydroxytyrosol (HT) reduce α-Syn toxicity. Their effect on the vitagenes system of PC12 cells have not been explored yet. These bioactive can cross the blood brain barrier (BBB). Therefore, this work aims to evaluate the inhibitory and destabilising capacities of MEL, PCA, HT, and their combinations on α-Syn kinetics and effects on vitagenes system (sirtuin-1 (SIRT-1), sirtuin-2 (SIRT-2), heme oxygenase (HO-1) and heat shock protein 70 (Hsp-70)). In vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis, MTT assay and qPCR) were used. Compounds, both individually and simultaneously were able to decrease the toxicity induced by α-Syn. Concurrently, occurrence of PCA (100 μM) +HT (100 μM) showed the highest inhibitory effect against α-Syn fibril formation and destabilisation of α-Syn fibrils (88 and 62%, respectively). Moreover, these compounds increased the expression of SIRT-2, HO-1 and Hsp70, contributing to a neuroprotective effect. In addition, the most important result is the increase on the expression of SIRT-2 caused by the combination of MEL + HT + PCA in the absence of α-Syn fibrils.
•Melatonin (MEL), Protocatechuic acid (PCA) and hydroxytyrosol (HT) increased the expression of SIRT-2, HO-1 and Hsp70.•PCA (100 μM) +HT (100 μM) had the highest inhibitory effect against α-Syn fibril formation & destabilisation of α-Syn fibrils.•MEL, PCA and HT present neuroprotective effects against α-Syn toxicity increasing PC12 cell viability.
•HT is a potent inhibitor of α-syn fibril formation.•α-Syn fibrils can be effectively destabilised by HT.•HT completely counteracts the neurotoxicity induced by α-syn.•HT is a promising compound for ...developing strategies to tackle PD.
Stilbenes are phenolic compounds present in different higher plant families that have shown different biological activities, such as antioxidant properties and antitumoral and anti-atherosclerotic ...effects, among others. Angiogenesis is a key process involved in both cancer and cardiovascular diseases, the vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 being the main triggers. Certain polyphenol compounds, such as flavonoids, have shown a potent capacity to inhibit VEGF and, consequently, angiogenesis. The present work, therefore, aims to evaluate the potential effect of stilbenes on inhibiting VEGF and their subsequent effect on the downstream signaling pathway (PLCγ1, Akt, and eNOS). VEGFR-2 activation was studied through an ELISA assay in the HUVEC line, while the phosphorylation of intracellular downstream proteins PLCγ1, Akt, and eNOS was tested by Western blot. Student’s t test was used to determine significant differences between samples. On the one hand, astringin, pallidol, and ω-viniferin showed the lowest IC50 values (2.90 ± 0.27, 4.42 ± 0.67, and 6.10 ± 1.29 μM, respectively) against VEGFR-2 activation. Additionally, VEGF-induced PLCγ1 phosphorylation was significantly inhibited by ε-viniferin, astringin, and ω-viniferin. However, ε-viniferin and pallidol simultaneously enhanced eNOS activation, proving to be via Akt activation in the case of ε-viniferin. For the first time, these data suggest that stilbenes such as astringin, pallidol, ω-viniferin, and ε-viniferin have a potential anti-angiogenic effect and they could be further considered as anti-VEGF ingredients in food and beverages. In addition, ε-viniferin and pallidol significantly allowed eNOS activation and could likely prevent the side effects caused by anti-VEGF hypertension drugs.
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