Identification of compounds present in lipophilic extracts from Brachystola magna (Girard): substances with potential healing properties.

Insects from the Orthoptera order possess important biological activities such as wound healing and represent a therapeutic resource in traditional medicine worldwide. Hence, this study addressed the characterisation of lipophilic extracts from Brachystola magna (Girard), identifying compounds with potential healing properties. For that, four extracts were obtained from sample 1 (head-legs) and sample 2 (abdomen): extract A (hexane/sample 1), extract B (hexane/sample 2), extract C (ethyl acetate/sample 1) and extract D (ethyl acetate/sample 2). All extracts were analysed by Gas Chromatography-Mass Spectrometry (GC-MS), Gas Chromatography-Flame Ionization Detection (GC-FID) and Fourier-Transform Infrared Spectroscopy (FTIR). Compounds identified were squalene, cholesterol and fatty acids, having a higher concentration of linolenic acid in extracts A and B, while extracts C and D had a higher content of palmitic acid. Additionally, FTIR detected characteristic peaks of lipids and triglycerides. Components of the lipophilic extracts suggested that this product could be used for skin illnesses treatment.

Possible Signaling Pathways in the Gut Microbiota-Brain Axis for the Development of Parkinson's Disease Caused by Chronic Consumption of Food Additives.

It is well-known that consumption of synthetic and natural food additives has both positive and negative effects in the human body. However, it is not clear yet how food additives are related to the development of Parkinson's disease. Therefore, in this review work, the food additive effects related to the gut microbiota-brain axis and the processes that are carried out to develop Parkinson's disease are studied. To this end, a systematic literature analysis is performed with the selected keywords and the food additive effects are studied to draw possible routes of action. This analysis leads to the proposition of a model that explains the pathways that relate the ingestion of food additives to the development of Parkinson's disease. This work motivates further research that ponders the safety of food additives by measuring their impacts over the gut microbiota-brain axis.

Chronic consumption of food-additives lead to changes via microbiota gut-brain axis.

Some food additives have demonstrated to induce dysbiosis leading to the development gut and gastrointestinal diseases. In order to clarify how this dysbiosis affects the microbiota gut-brain axis, a systematic interpretative literature review is carried out in this work. This review was made in seven academic search engines using the keywords shown below. The main finding of this work is a clear link between the changes in the gut microbiota promoted by food additives and the causes that lead to many reported diseases related to chronic food additives consumption. Despite the findings, studies on the effects of food additives on microbiota are still insufficient. Therefore, this work should serve as a motivation for future research on this subject.

Irreversible disruption of the cytoskeleton as induced by non-cytotoxic exposure to titanium dioxide nanoparticles in lung epithelial cells.

Exposure to TiO2 NPs induces several cellular alterations after NPs uptake including disruption of cytoskeleton that is crucial for lung physiology but is not considered as a footprint of cell damage. We aimed to investigate cytoskeleton disturbances and the impact on cell migration induced by an acute TiO2 NPs exposure (24 h) and the recovery capability after 6 days of NPs-free treatment, which allowed investigating if cytoskeleton damage was reversible. Exposure to TiO2 NPs (10 µg/cm2) for 24 h induced a decrease 20.2% and 25.1% in tubulin and actin polymerization. Exposure to TiO2 NPs (10 µg/cm2) for 24 h followed by 6 days of NPs-free had a decrease of 26.6% and 21.3% in tubulin and actin polymerization, respectively. The sustained exposure for 7 days to 1 µg/cm2 and 10 µg/cm2 induced a decrease of 22.4% and 30.7% of tubulin polymerization respectively, and 28.7% and 46.2% in actin polymerization. In addition, 24 h followed 6 days of NPs-free exposure of TiO2 NPs (1 µg/cm2 and 10 µg/cm2) decreased cell migration 40.7% and 59.2%, respectively. Cells exposed (10 µg/cm2) for 7 days had a decrease of 65.5% in cell migration. Ki67, protein surfactant B (SFTPB) and matrix metalloprotease 2 (MMP2) were analyzed as genes related to lung epithelial function. The results showed a 20% of Ki67 upregulation in cells exposed for 24 h to 10 µg/cm2 TiO2 NPs while a downregulation of 20% and 25.8% in cells exposed to 1 µg/cm2 and 10 µg/cm2 for 24 h followed by 6 days of NPs-free exposure. Exposure to 1 µg/cm2 and 10 µg/cm2 for 24 h and 7 days upregulates SFTPB expression in 53% and 59% respectively, MMP2 expression remain unchanged. In conclusion, exposure of TiO2 NPs affected cytoskeleton of lung epithelial cells irreversibly but this damage was not cumulative.

Influence of shape and dispersion media of titanium dioxide nanostructures on microvessel network and ossification.

Titanium dioxide nanoparticles (TiO2 NPs) production has been used for pigment, food and cosmetic industry and more recently, shaped as belts for treatment of contaminated water, self-cleaning windows and biomedical applications. However, the toxicological data have demonstrated that TiO2 NPs inhalation induce inflammation in in vivo models and in vitro exposure leads to cytotoxicity and DNA damage. Dermal exposure has limited adverse effects and the possible risks for implants used for tissue regeneration is still under research. Then, it has been difficult to establish a straight statement about TiO2 NPs toxicity since route of exposure and shapes of nanoparticles play an important role in the effects. In this study we aimed to investigate the effect of three different types of TiO2 NPs (industrial, food-grade and belts) dispersed in fetal bovine serum (FBS) and saline solution (SS) on microvessel network, angiogenesis gene expression and femur ossification using a chick embryo model after an acute exposure of NPs on the day 7 after eggs fertilization. Microvascular density of chorioallantoic membrane (CAM) was analyzed after 7days of NPs injection and vehicles induced biological effects per se. NPs dispersed in FBS or SS have slight differences in microvascular density, mainly opposite effect on angiogenesis gene expression and no effects on femur ossification for NPs dispersed in SS. Interestingly, NPs shaped as belts dramatically prevented the alterations in ossification induced by FBS used as vehicle.

Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases.

Cell cycle synchronization reveals greater G2/M-phase accumulation of lung epithelial cells exposed to titanium dioxide nanoparticles.

Titanium dioxide has been classified in the 2B group as a possible human carcinogen by the International Agency for Research on Cancer, and amid concerns of its exposure, cell cycle alterations are an important one. However, several studies show inconclusive effects, mainly because it is difficult to compare cell cycle effects caused by TiO2 nanoparticle (NP) exposure between different shapes and sizes of NP, cell culture types, and time of exposure. In addition, cell cycle is frequently analyzed without cell cycle synchronization, which may also mask some effects. We hypothesized that synchronization after TiO2 NP exposure could reveal dissimilar cell cycle progression when compared with unsynchronized cell population. To test our hypothesis, we exposed lung epithelial cells to 1 and 10 µg/cm(2) TiO2 NPs for 7 days and one population was synchronized by serum starvation and inhibition of ribonucleotide reductase using hydroxyurea. Another cell population was exposed to TiO2 NPs under the same experimental conditions, but after treatments, cell cycle was analyzed without synchronization. Our results showed that TiO2 NP-exposed cells without synchronization had no changes in cell cycle distribution; however, cell population synchronized after 1 and 10 µg/cm(2) TiO2 NP treatment showed a 1.5-fold and 1.66-fold increase, respectively, in proliferation. Synchronized cells also reveal a faster capability of TiO2 NP-exposed cells to increase cell population in the G2/M phase in the following 9 h after synchronization. We conclude that synchronization discloses a greater percentage of cells in the G2/M phase and higher proliferation than TiO2 NP-synchronized cells.

Nrf2 protects the lung against inflammation induced by titanium dioxide nanoparticles: A positive regulator role of Nrf2 on cytokine release.

Titanium dioxide nanoparticles (TiO2 NPs) have been classified as possibly carcinogenic to humans and they are an important nanomaterial widely used in pharmaceutical and paint industries. Inhalation is one of the most important routes of exposure in occupational settings. Several experimental models have shown that oxidative stress and inflammation are key mediators of cell damage. In this regard, Nrf2 modulates cytoprotection against oxidative stress and inflammation, however, its role in inflammation induced by TiO2 NPs exposure has been less investigated. The aim of this work was to investigate the role of Nrf2 in the cytokines produced after 4 weeks of TiO2 NPs exposure (5 mg/kg/2 days/week) using wild-type and Nrf2 knockout C57bl6 mice. Results showed that Nrf2 protects against inflammation and oxidative damage induced by TiO2 NPs exposure, however, Nrf2 is a positive mediator in the expression of IFN-γ, TNF-α, and TGF-ß in bronchial epithelium and alveolar space after 4 weeks of exposure. These results suggest that Nrf2 has a central role in up-regulation of cytokines released during inflammation induced by TiO2 NPs and those cytokines are needed to cope with histological alterations in lung tissue.

Titanium dioxide nanoparticles induce an adaptive inflammatory response and invasion and proliferation of lung epithelial cells in chorioallantoic membrane.

Titanium dioxide nanoparticles (TiO2 NPs) studies have been performed using relatively high NPs concentration under acute exposure and limited studies have compared shape effects. We hypothesized that midterm exposure to low TiO2 NPs concentration in lung epithelial cells induces carcinogenic characteristics modulated partially by NPs shape. To test our hypothesis we synthesized NPs shaped as belts (TiO2-B) using TiO2 spheres (TiO2-SP) purchased from Sigma Aldrich Co. Then, lung epithelial A549 cells were low-exposed (10 µg/cm(2)) to both shapes during 7 days and internalization, cytokine release and invasive potential were determined. Results showed greater TiO2-B effect on agglomerates size, cell size and granularity than TiO2-SP. Agglomerates size in cell culture medium was 310 nm and 454 nm for TiO2-SP and TiO2-B, respectively; TiO2-SP and TiO2-B induced 23% and 70% cell size decrease, respectively, whilst TiO2-SP and TiO2-B induced 7 and 14-fold of granularity increase. NOx production was down-regulated (31%) by TiO2-SP and up-regulated (70%) by TiO2-B. Both NPs induced a transient cytokine release (IL-2, IL-6, IL-8, IL-4, IFN-γ, and TNF-α) after 4 days, but cytokines returned to basal levels in TiO2-SP exposed cells while TiO2-B induced a down-regulation after 7 days. Midterm exposure to both shapes of NPs induced capability to degrade cellular extracellular matrix components from chorioallantoic membrane and Ki-67 marker showed that TiO2-B had higher proliferative potential than TiO2-SP. We conclude that midterm exposure to low NPs concentration of NPs has an impact in the acquisition of new characteristics of exposed cells and NPs shape influences cellular outcome.

Decrease in respiratory function and electron transport chain induced by airborne particulate matter (PM10) exposure in lung mitochondria.

Particulate matter, with a mean aerodynamic diameter of ≤10 µm (PM10), exposure is considered as a risk factor for cardiovascular and respiratory diseases. The mechanism of cell damage induced by PM10 exposure is related to mitochondrial alterations. The aim of this work was to investigate the detailed alterations induced by PM10 on mitochondrial function. Since lung tissue is one of the most important targets of PM10 inhalation, isolated mitochondria from lung rat tissue were exposed to PM10 and structural alterations were analyzed by transmission electron microscopy. Mitochondrial function was evaluated by respiratory control index (RCI), membrane potential, adenosine triphosphate (ATP) synthesis, and activity of respiratory chain. Results showed that exposure to PM10 in isolated mitochondria from lung tissue caused enlarged intermembrane spaces and shape alterations, disruption of cristae, and the decrease in dense granules. Oxygraphic traces showed a concentration-dependent decrease in oxygen consumption and RCI. In addition, mitochondrial membrane potential, ATP synthesis, and activity of complexes II and IV showed an increase and decrease, respectively, after PM10 exposure. PM10 exposure induced disruption in structure and function in isolated mitochondria from lung rat tissue.

Titanium dioxide nanoparticles impair lung mitochondrial function.

Titanium dioxide nanoparticles (TiO(2) NPs) are used in an increasing number of human products such as cosmetics, sunscreen, toothpaste and paints. However, there is clear evidence about effects associated to TiO(2) NPs exposure, which include lung inflammation and tumor formation and these effects are related to reactive oxygen species (ROS) formation. The ROS generation could be attributed to a mitochondrial dysfunction. Even though, it has been shown that TiO(2) NPs exposure can induce some alterations in mitochondria including cytochrome c release to cytosol, change in mitochondrial permeability and decrease of mitochondrial membrane potential (ΔΨ(m)), there is no information about the changes in mitochondrial function induced by TiO(2) NPs. We hypothesized that TiO(2) NPs effects are associated with mitochondrial dysfunction and redox unbalance. To test our hypothesis we isolated mitochondria from lung tissue of rats and exposed them to 10(g TiO(2) NPs (particle size<25nm)/mg protein for 1h. Our results showed that TiO(2) NPs decreases NADH levels and impairs ΔΨ(m) and mitochondrial function accompanied by ROS generation during mitochondrial respiration.