Neuroprotective role of lactate in a human in vitro model of the ischemic penumbra

In patients suffering from cerebral ischemic stroke, there is an urgent need for treatments to protect stressed yet viable brain cells. Recently, treatment strategies that induce neuronal activity have been shown to be neuroprotective. Here, we hypothesized that neuronal activation might maintain or trigger the astrocyte-to-neuron lactate shuttle (ANLS), whereby lactate is released from astrocytes to support the energy requirements of ATP-starved hypoxic neurons, and this leads to the observed neuroprotection. We tested this by using a human cell based in vitro model of the ischemic penumbra and investigating whether lactate might be neuroprotective in this setting. We found that lactate transporters are involved in the neuroprotective effect mediated by neuronal activation. Furthermore, we showed that lactate exogenously administered before hypoxia correlated with neuroprotection in our cellular model. In addition, stimulation of astrocyte with consequent endogenous production of lactate resulted in neuroprotection. To conclude, here we presented evidence that lactate transport into neurons contributes to neuroprotection during hypoxia providing a potential basis for therapeutic approaches in ischemic stroke.</p

Prunus persica var. platycarpa (Tabacchiera Peach): bioactive compounds and antioxidant activity of pulp, peel and seed ethanolic extracts

A comparative analysis of ethanol extracts from peel, pulp and seed of Prunus persica var. platycarpa (Tabacchiera peach) was done. The total phenols, flavonoids and carotenoids content as well as the antioxidant properties were evaluated. Peach pulp extract was characterized by the highest total phytonutrients content and exhibited the highest antioxidant activity in all in vitro assays. Interestingly, pulp extract showed IC50 values of 2.7 and 2.2 g/mL at 30 and 60 minutes of incubation, respectively using -carotene bleaching test. A remarkable result was also obtained by using Fe-chelating assay (IC50 of 2.9 g/mL vs 1.3 g/mL for positive control BHT). Pulp extract was subjected to liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS). Six main compounds, namely gallic acid, protocatechuic acid, protocatechualdehyde, chlorogenic acid, p-coumaric acid, and ferulic acid, were identified. Overall, the results suggest that Prunus persica var. platycarpa displays a good antioxidant activity and its consumption could be promote

Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs:A Valid Platform for Functional Tests

: With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing

Spent espresso coffee grounds as a source of anti-proliferative and antioxidant compounds

Disposal of spent espresso coffee grounds (SCG) is costly and leads to the loss of bioactive compounds that could be fractionated, in several applications. This work aimed to investigate phenolic profile, tocopherols, and antioxidant and anti-proliferative activities of SCGs ethanolic extracts from coffee powders differing in coffee provenience and composition (arabica/robusta). Tyrosol, detected for the first time in SCGs, was the most abundant phenolic measured (121-1,084 mg/kg in the extract), along with 4-hydroxybenzoic acid and vanillin (885-1813 and 340-1103 mg/kg, respectively). Extract derived from 100% robusta from Guatemala (S7-R) showed the highest α- to ß-tocopherol ratio of 1.2 and the highest antioxidant potential as evidenced by RACI and GAS values of -0.43 and 0.20, respectively. Moreover, S7-R showed a promising anti-proliferative activity toward human lung carcinoma cells (A549), with IC50 value of 61.2 ug/mL comparable to that given by the positive control vinblastine (IC50 value of 67.3 ug/mL)