Microfluidic-derived docosahexaenoic acid liposomes for glioblastoma therapy.

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor and currently lacks an effective treatment. In this study, we utilized a microfluidic system to synthesize docosahexaenoic acid (DHA) liposomes for GBM therapy. DHA is an omega-3 (ω3) polyunsaturated fatty acid commonly found in human dietary consumption that has demonstrated potential in mitigating cancer development. The microfluidic device employed allowed for precise fine-tuning of the physicochemical properties of liposomes by adjusting the flow rate ratios, flow rates, and lipid concentrations. Three distinct-sized liposomes, ranging from 80 nm and 130 nm, were successfully internalized by GBM cells, and demonstrated the ability to reduce the viability of these cells. Furthermore, DHA liposomes proved significantly more efficient in triggering apoptotic pathways, through caspase-3-dependent mechanisms, in comparison to free DHA. Thus, the nanomedicine platform established in this study presents new opportunities in the development of liposome formulations incorporating ω3 fatty acids for cancer therapy.

The influence of physical activity level on the length of stay in hospital in older men survivors of COVID-19.

The purpose of this study was to verify the influence of physical activity level on the length of hospital stay in older men recovered from COVID-19. In total, 126 older men diagnosed with COVID-19 were admitted to the hospital between September and December 2020. Among them, 70 survived, of which 39 older men were included in the study. Within 30 days after discharge, patients answered the International Physical Activity Questionnaire to measure their physical activity level through phone contact, with questions corresponding to the week before symptom onset. Clinical and laboratorial data from admission, days between onset of symptoms and admission, length of stay, computed tomography abnormalities, and the need for the intensive care unit were collected. The groups (active × sedentary) were compared using the Student t test or Mann-Whitney test for quantitative data and chi-square test was used for categorical data. There is no difference between the groups in characteristics of admission (p > 0.05), except by potassium level. Active older men had a shorter length of stay (6.50 ± 3.46 vs 11.48 ± 7.63 days; p = 0.03), disease duration (15.71 ± 4.84 vs 21.09 ± 7.69 days; p = 0.02), and lower frequency of lung damage when compared to their sedentary counterparts. In conclusion, being physically active prior to infection can attenuate length of hospital stay in older men with COVID-19.

Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators.

Different types of memory are thought to rely on different types of synaptic plasticity, many of which depend on the activation of the N-Methyl-D Aspartate (NMDA) subtype of glutamate receptors. Accordingly, there is considerable interest in the possibility of using positive allosteric modulators (PAMs) of NMDA receptors (NMDARs) as cognitive enhancers. Here we firstly review the evidence that NMDA receptor-dependent forms of synaptic plasticity: short-term potentiation (STP), long-term potentiation (LTP) and long-term depression (LTD) can be pharmacologically differentiated by using NMDAR ligands. These observations suggest that PAMs of NMDAR function, depending on their subtype selectivity, might differentially regulate STP, LTP and LTD. To test this hypothesis, we secondly performed experiments in rodent hippocampal slices with UBP714 (a GluN2A/2B preferring PAM), CIQ (a GluN2C/D selective PAM) and UBP709 (a pan-PAM that potentiates all GluN2 subunits). We report here, for the first time, that: (i) UBP714 potentiates sub-maximal LTP and reduces LTD; (ii) CIQ potentiates STP without affecting LTP; (iii) UBP709 enhances LTD and decreases LTP. We conclude that PAMs can differentially regulate distinct forms of NMDAR-dependent synaptic plasticity due to their subtype selectivity.

The impact of Mesenchymal Stem Cells and their secretome as a treatment for gliomas.

In recent years, we have witnessed a significant increase in the amount of studies using Mesenchymal Stem Cells (MSCs) for cancer therapy, mostly as vectors for drug or gene delivery strategies. This is because of their intrinsic capacity of homing into tumor niches. However, the interactions between MSCs themselves and tumor cells is not fully understood, with contradictory results frequently being observed regarding their effects on cancer cell invasion and proliferation. This poses an important question of safety in respect to the application of these cells. The source of the MSC population used, as well as the type of cancer cells under study might strongly influence this interaction. Moreover, differences in isolation protocols, culture media compositions, time of culture and conditioned media collection, or even timing and mode of MSCs administration to in vivo models of cancer may also affect the interaction MSC-tumor cells. In this review, we drive our focus into malignant brain tumors, particularly gliomas, one of the deadliest forms of cancer. Moreover, we look with some detail into different studies using MSCs as a treatment for brain tumors and compare them, highlighting the main deviations and similarities among them.

Vitis labrusca leaf extract prevents pentylenetetrazol-induced oxidative damage but not seizures in rats.

Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favorably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the possible anticonvulsant and antioxidant effects of a leaf extract of Vitis labrusca in an animal model of seizures induced by pentylenetetrazole (PTZ). The animals received injections of V. labrusca extract (10, 30 and 100 mg/kg) or vehicle and, 30 minutes later, they received an injection of PTZ, and were then observed for 30 minutes. The latency time and tonic—clonic seizure time were registered. Oxidative damage in lipids and proteins was quantified in the cerebellum, cerebral cortex and hippocampus. It was observed that the leaf extract were capable of reducing lipid peroxidation and protein oxidation caused by PTZ at all doses tested.

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids.

Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.

Evaluation of the start-up of an integrated municipal solid waste and leachate treatment system.

A pilot-scale experiment was set up in the laboratory with the purpose of investigating the most relevant aspects of the anaerobic digestion of municipal solid wastes (MSW), which are necessary for the preparation of future feasibility studies and cost-benefit analyses. The experiment consisted of a comparative analysis among three different lines of operation, each one consisting of three anaerobic MSW reactors (with unit volume of 700 L): conventional landfill (line 1), raw leachate recycling (line 2), and integrated treatment, with seeded leachate recycling (line 3). So, a UASB reactor was installed in the integrated treatment line with the purpose of removing the organic load of the leachate of the MSW reactors and utilising the biological sludge produced for inoculation of the waste digestion. The endogenous inoculation promoted in line 3, by means of recirculation of the leachate and return of the exceeding biological sludge produced in the UASB reactor, has favoured the initial fermentation stage and also the acceleration of the methanogenic phase.