Safety profile and prevention of cognitive deficit in alzheimer’s disease model of graphene family nanomaterials, Tucuma oil (Astrocaryum Vulgare) and its synergisms

Alzheimer\u27s disease is a worldwide health issue, and there are currently no treatments that can stop this disease. Oxidized graphene derivatives have gained prominence in use in biological systems due to their excellent physical-chemical characteristics, biocompatibility and ability to overcome the blood-brain barrier. Other substances highlighted are those of natural origin from the Amazon biome, such as tucuma, a fruit whose oil has been widely studied in therapeutic applications. Thus, the aim of this study was to investigate the action of graphene oxide, reduced graphene oxide and tucuma oil, isolated and combined, as an alternative for treatment of Alzheimer\u27s disease through studies in silico, in vitro, in vivo and ex vivo. Computational simulation via docking was used to verify the affinity of the substances with the proteins β-amyloid and acetylcholinesterase, in which the reduced graphene oxide was the one that showed the most favorable interaction. The results of the ab initio simulation showed that the synergism between the nanostructures and the oil occurs through physical adsorption. The experimental results revealed that the substances and their combinations were nontoxic, both at the cellular and systemic level. In general, all treatments had positive results against induced memory deficit, but reduced graphene oxide was the most prominent, as it was able to protect against memory damage in all behavioral tests performed, with anticholinesterase activity and antioxidant effect. In conclusion, the reduced graphene oxide is, among the treatments studied, the one with great therapeutic potential to be investigated in the treatment of this disease

Effects of nanocapsules containing all-trans-retinoic acid under hemolytic and coagulation activity

The chemotherapeutic all-trans retinoic acid (ATRA) used in the treatment of Acute Promyelocytic Leukemia has adverse effects on its oral administration, with which we incorporated a system of drugs, the nanocapsules, in order to have a possible improvement in solubility, photosensitivity, lower toxicity, generating pharmacological efficacy. The objective was to evaluate and compare the hemolytic and coagulation activity of the free drug (AL), nanoencapsulated (NA) and the white nanocapsules (NB) by analyzing the results of hemolysis, Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT). We developed a prospective study of treatments at different concentrations of 0.25; 0.5; 1.0; 1.5; 2.0; 2.5 μg/mL. For the first test, all concentrations showed hemolytic activity, but when compared to NA with ATRA it is observed that these carriers induced lower hemolytic toxicity. In the PT test the nanoparticles at the two lowest concentrations remained in the physiological range (12 - 15 seconds). For the APTT test the three lowest concentrations remained within the control (25 - 35 seconds). Thus, we believe there is a promising benefit of using these nanoparticles developed and no doubt further studies will be performed to confirm the responses obtained here

Bioavailable phenolic compounds from olive pomace present anti-neuroinflammatory potential on microglia cells

The neuroinflammatory process is considered one of the main characteristics of central nervous system diseases, where a pro-inflammatory response results in oxidative stress through the generation of reactive oxygen and nitrogen species (ROS and RNS). Olive (Olea europaea L.) pomace is a by-product of olive oil production that is rich in phenolic compounds (PCs), known for their antioxidant and anti-inflammatory properties. This work looked at the antioxidant and anti-neuroinflammatory effects of the bioavailable PC from olive pomace in cell-free models and microglia cells. The bioavailable PC of olive pomace was obtained through the process of in vitro gastrointestinal digestion of fractionated olive pomace (OPF, particles size < 2 mm) and micronized olive pomace (OPM, particles size < 20 µm). The profile of the PC that is present in the bioavailable fraction as well as its in vitro antioxidant capacity were determined. The anti-neuroinflammatory capacity of the bioavailable PC from olive pomace (0.03–3 mg L−1 ) was evaluated in BV-2 cells activated by lipopolysaccharide (LPS) for 24 h. The total bioavailable PC concentration and antioxidant activity against peroxyl radical were higher in the OPM than those observed in the OPF sample. The activation of BV-2 cells by LPS resulted in increased levels of ROS and nitric oxide (NO). The bioavailable PCs from both OPF and OPM, at their lowest concentrations, were able to reduce the ROS generation in activated BV-2 cells. In contrast, the highest PC concentration of OPF and OPM was able to reduce the NO levels in activated microglial cells. Our results demonstrate that bioavailable PCs from olive pomace can act as anti-neuroinflammatory agents in vitro, independent of particle size. Moreover, studies approaching ways to increase the bioavailability of PCs from olive pomace, as well as any possible toxic effects, are needed before a final statement on its nutritional use is made

Human adipose-derived stem cells obtained from lipoaspirates are highly susceptible to hydrogen peroxide mediated cytogenotoxicity

There is evidence that H2O2 can induce the proliferation, migration, and regeneration of stem cells, as well as that of adipose-derived stem cells (ASCs). This could be useful to expand the possible uses of ASCs in therapeutic applications. &nbsp;However, the safety profile of H2O2 use in stem cells is not clear yet. Therefore, the present study evaluated the acute cytotoxic, oxidative and genotoxic effects of different concentrations of H2O2 on ASCs obtained from human lipoaspirates. The ASCs were treated with 1–1000 μM H2O2 for two hours. Cell viability was evaluated by double-strand DNA determination. Apoptosis induction was analyzed measuring active levels of caspases 1, 3 and 8. Biochemical oxidative stress markers were analyzed and genotoxic effects were assessed by DNA comet assay. All H2O2 concentrations increased ASC mortality rates with approximately 100% mortality achieved at ≥ 200 μM. Active caspases 1, 3 and 8, oxidative stress, as well as oxidative damage as assessed by lipid peroxidation increased dose‐dependently. There was also an approximate 50% increase in catalase levels in cells exposed to all H2O2 tested concentrations. H2O2 concentrations of ≥ 10 μM were genotoxic. These results suggest that ASCs are highly sensitive to H2O2 exposition. In addition, DNA damage in the surviving cells may affect their proliferative and differentiation capacity, as well as their safety profile for therapeutic use

A Dynamic Protocol to Explore NLRP3 Inflammasome Activation in Cerebral Organoids

The NLRP3 inflammasome plays a crucial role in the inflammatory response, reacting to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This response is essential for combating infections and restoring tissue homeostasis. However, chronic activation can lead to detrimental effects, particularly in neuropsychiatric and neurodegenerative diseases. Our study seeks to provide a method to effectively measure the NLRP3 inflammasome’s activation within cerebral organoids (COs), providing insights into the underlying pathophysiology of these conditions and enabling future studies to investigate the development of targeted therapies

Sistema olivococlear medial e genotoxicidade em escolares de região fumicultora

OBJETIVO: avaliar a associa&#231;&#227;o entre a fun&#231;&#227;o do sistema olivococlear medial e biomarcadores genot&#243;xicos em escolares residentes de regi&#227;o fumicultora. M&#201;TODOS: trata-se de um estudo observacional, prospectivo e transversal. O grupo estudo foi composto por 21 escolares normo-ouvintes residentes de regi&#227;o fumicultora e o grupo controle por 25 escolares normo-ouvintes que n&#227;o residiam na zona rural. O sistema olivococlear medial foi avaliado por meio da supress&#227;o das Emiss&#245;es otoac&#250;sticas produto de distor&#231;&#227;o, e os biomarcadores genot&#243;xicos foram: ensaio cometa, teste de micron&#250;cleos e ensaio fluorim&#233;trico de quantifica&#231;&#227;o de DNA. Os dados obtidos foram submetidos &#224; an&#225;lise estat&#237;stica. RESULTADOS: ao comparar a ocorr&#234;ncia do efeito de supress&#227;o das emiss&#245;es entre os grupos, n&#227;o foi detectada associa&#231;&#227;o significante. Tanto no ensaio cometa como no ensaio fluorim&#233;trico de quantifica&#231;&#227;o de DNA a m&#233;dia do grupo estudo mostrou-se significantemente mais elevada que a do grupo controle. No teste de micron&#250;cleos, verificou-se diferen&#231;a significante quanto ao somat&#243;rio de c&#233;lulas alteradas e &#224; frequ&#234;ncia de c&#233;lulas binucleadas, sendo a m&#233;dia do grupo estudo mais elevada que a do grupo controle. J&#225; referente &#224; frequ&#234;ncia de c&#233;lulas com micron&#250;cleo, n&#227;o se observou diferen&#231;a significante entre os grupos. N&#227;o foi detectada associa&#231;&#227;o entre ocorr&#234;ncia do efeito de supress&#227;o e os resultados dos biomarcadores genot&#243;xicos. CONCLUS&#195;O: o grupo estudo n&#227;o apresentou altera&#231;&#245;es no sistema olivococlear medial, evidenciado pela presen&#231;a de supress&#227;o das emiss&#245;es, por&#233;m apresentou &#237;ndices de dano significantemente mais elevados dos biomarcadores genot&#243;xicos. Entretanto, n&#227;o se verificou associa&#231;&#227;o entre supress&#227;o das emiss&#245;es e genotoxicidade

Otoacoustic emissions and biomarkers of oxidative stress in students of a tobacco-producing region

PURPOSE: To verify the association between the amplitude of distortion-product otoacoustic emissions (DPOAE) and biomarkers of oxidative stress (OS) in resident students of the tobacco-producing region. METHODS: Participated in the study group (SG) 21 normal-hearing students from the tobacco-producing region, and in the control group (CG) 25 normal-hearing students who did not live in the countryside. The auditory system was assessed by DPOAE and the following biomarkers: dichlorofluorescein diacetate (DCFH-DA) and micronucleus test (MN). RESULTS: Both groups showed DPOAE present in both ears. Significant difference was detected between groups - in the right ear in the frequency of 4.000 Hz and in the left ear in the frequency of 2.000 Hz - with the mean amplitude of the DPOAE of the SG lower than the one found in the CG. Considering both ears, the SG presented lower mean across all frequencies and it was found a significant difference in the frequencies of 2.000 and 4.000 Hz. The overall mean of DPOAE, by ear, no significant differences were observed. In relation to the rate of production of free radicals, the mean of the SG was significantly higher than that of the mean of the CG. For the frequency of abnormal cells in the MN test, the mean of the SG was also considerate significantly higher than the mean of the CG. CONCLUSION: The SG showed a lower response level of DPOAE at all frequencies and high levels of biomarkers of EO, however there was no association between assessments

Toxicity and oxidative stress of canine mesenchymal stromal cells from adipose tissue in different culture passages

Abstract: Stem cells in regenerative therapy have received attention from researchers in recent decades. The culture of these cells allows studies about their behavior and metabolism. Thus, cell culture is the basis for cell therapy and tissue engineering researches. A major concern regarding the use of cultivated stem cell in human or veterinary clinical routine is the risk of carcinogenesis. Cellular activities require a balanced redox state. However, when there is an imbalance in this state, oxidative stress occurs. Oxidative stress contributes to cytotoxicity, which may result in cell death or genomic alterations, favoring the development of cancer cells. The aim of this study was to determine whether there are differences in the behavior of cultured mesenchymal stem cells from canine adipose tissue according to its site of collection (omentum and subcutaneous) evaluating the rate of proliferation, viability, level of oxidative stress and cytotoxicity over six passages. For this experiment, two samples of adipose tissue from subcutaneous and omentum where taken from a female dog corpse, 13 years old, Pitbull. The results showed greater levels of oxidative stress in the first and last passages of both groups, favoring cytotoxicity and cell death