The effect of acute exposure of yellowtail tetra fish Astyanax lacustris (Lütken, 1875) to the glyphosate-based herbicide Templo®.

The herbicide glyphosate (N-(phosphonomethyl)glycine) efficiently eliminates weeds, is frequently present in surface waters, and may damage the health of various non-target organisms. The main objective of this study was to investigate cytotoxic and genotoxic effects in erythrocytes, DNA, and chromosomes of native South American fish Astyanax lacustris exposed to a glyphosate-based commercial herbicide Templo®. The presenty study evaluated the presence of micronuclei (MN), chromosomal aberrations (CA), DNA damage revealed by comet assay, and cellular morphological changes (CMC) as biomarkers. The A. lacustris specimens were exposed to Templo® for 96 h at concentrations below the permitted Brazilian legislation for freshwater environments. The glyphosate-based herbicide caused MN formation, an increased incidence of CA, DNA damage, and several types of CMC in all tested concentrations on A. lacustris. Notably, analyses were significant (p<0.05) for all concentrations, except in the frequency mean of MN at 3.7 µg/L. Thus, considering the intensive use of commercial glyphosate formulations in crops, the herbicide Templo® represents a potential risk of genotoxicity and cytotoxicity for aquatic organisms. Therefore, environmental protection agencies must review regulations for glyphosate-based herbicides in freshwater environments.

Copaiba oil's bactericidal activity and its effects on health and zootechnical performance for Nile tilapia after oral supplementation.

Tilapia is one of the most important farmed fish in the world and the most cultivated in Brazil. The increase of this farming favors the appearance of diseases, including bacterial diseases. Therefore, the aim of this study was to evaluate the bactericidal activity of copaiba oil, Copaifera duckei, against Streptococcus agalactiae and Flavobacterium columnare and the dietary effect of copaiba oil on zootechnical performance, hematological, biochemical, immunological, and histological analysis before and after an intraperitoneal infection (body cavity) with S. agalactiae in Nile tilapia. For this, fish were randomly distributed into 15 fiber tanks in five treatments (0, 0.25, 0.50, 0.75, and 1.0%) and fed with a commercial diet supplemented with copaiba oil for 30 days. After this period, the fish were randomly redistributed for the experimental challenge with S. agalactiae into six treatments (T0, T1, T2, T3, T4, and T5), the fish were anesthetized, and blood samples were collected to assess hematological, biochemical, immunological, and histological parameters. Copaiba oil showed bactericidal activity against Streptococcus spp. and Flavobacterium spp. in vitro. In addition, concentrations of 0.75 and 1.0% of copaiba oil have an anti-inflammatory effect and improve hematological and immunological parameters, increasing leukocyte numbers, albumin, and serum lytic activity. Furthermore, there is an increase in the intestinal villus length and tissue damage in groups at concentrations of 0.75 and 1.0% of copaiba oil. In conclusion, copaiba oil presented bactericidal activity against Streptococcus spp. and Flavobacterium spp. in vitro, and oral supplementation at concentrations of 0.75 and 1.0% compared to the control group enhanced non-specific immune parameters and digestibility in Nile Tilapia.

Experimental investigation of the chaotification of a Duffing-like electronic oscillator under two-frequency excitation.

Two-frequency excitation has recently emerged as an efficient method to generate strong chaotification of Duffing and Duffing-like dynamical systems with both single- and double-well potentials. For the systems with a double-well potential, large continuous regions with robust chaos (chaotic attractor insensitive to changes in the system parameters) have been predicted to exist when the method is applied. Motivated by these theoretical results, in this work, we investigate experimentally the chaotification under two-frequency excitation of a simple electronic circuit analogous to the double-well Duffing oscillator. The experimental results confirm the theoretical expectations, and a strong chaotification is observed. Evidences are also presented that the chaotic attractor is robust. Therefore, the work establishes experimentally the two-frequency excitation as a simple and reliable method of chaotification. Furthermore, because of its ease of fabrication, the experimental results turn the particular circuit considered in this work into an interesting practical alternative as a reliable source of continuous-time chaotic signals.

Metritis and the uterine disease microbiome are associated with long-term changes in the endometrium of dairy cows†.

Cows with metritis (uterine disease) during the first 1 to 2 wk postpartum have lower pregnancy rates when inseminated later postpartum (typically >10 wk). We hypothesized that metritis and the disease-associated uterine microbiome have a long-term effect on endometrial gene expression. Changes in gene expression may inform a mechanism through which disease lowers pregnancy rates. A total of 20 cows were enrolled at 1 to 2 wk postpartum to either metritis (clinical disease; n = 10) or healthy (control; n = 10) groups and randomly assigned to be slaughtered at approximately 80 d and 165 d postpartum (mid-lactation). The microbiome of the reproductive tract was sampled to confirm the presence of pathogens that are typical of metritis. In addition to the original clinical diagnosis, study cows were retrospectively assigned to uterine-disease and control groups based on the composition of their microbiome. There was no effect of early postpartum uterine disease on the uterine microbiome at mid-lactation (time of slaughter). Nonetheless, early postpartum metritis and the disease microbiome were associated with a large number of differentially-expressed genes at mid-lactation primarily in the caruncular compared with the inter-caruncular endometrium. Gene enrichment analysis identified oxidative phosphorylation as the primary pathway increased in caruncular endometrium of diseased cows whereas growth factor signaling pathways were reduced. The current study demonstrated that metritis and a uterine disease microbiome leave a sustained imprint on gene expression in the caruncular endometrium that may explain lower fertility in cows with postpartum uterine disease.

Macrophage-derived human resistin promotes perivascular adipose tissue dysfunction in experimental inflammatory arthritis.

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.

The use of integrative tools and multiple models for aquatic environmental quality assessment: a case study of the Mirim Lagoon, Southern Brazil.

This study performed toxicity assays with microalgae, microcrustaceans, and fish as well as evaluated biochemical and behavioral biomarkers in fish and microcrustaceans to assess the quality of the surface water of Mirim Lagoon, which belongs to one of the largest hydrographic basins in the world, located in southern Brazil. Three distinct sampling periods were chosen (January, March, and June 2022) based on the rice plantation dynamics which is the main activity surrounding the lagoon. In January, the plantation is irrigated; in March, the water is drained into the Mirim Lagoon, and July is the off-season. Concerning toxicity tests, there was significant inhibition in microalgae growth when exposed to water collected in March, but no mortality was observed for Ceriodaphia dubia, Daphnia magna, and Danio rerio. Regarding biomarkers, behavioral variables contributed more to the higher values of the Integrated Biomarker Response (IBR) index for both D. magna and D. rerio, in March. The Redundancy Analysis (RDA) indicated a correlation between the biomarkers for both organisms and abiotic parameters, mainly nutrients (total phosphorus and total nitrogen), thermotolerant coliforms, total solids, and turbidity. Spatially, there was no difference during monitoring, but the most significant ecotoxicological effects were observed in March. Multivariate analysis and the IBR index proved to be useful tools for monitoring of water bodies such as Mirim Lagoon.

Pharmacological activation of nuclear factor erythroid 2-related factor-2 prevents hyperglycemia-induced renal oxidative damage: Possible involvement of O-GlcNAcylation.

Hyperglycemia is a major risk factor for kidney diseases. Oxidative stress, caused by reactive oxygen species, is a key factor in the development of kidney abnormalities related to hyperglycemia. The nuclear factor erythroid 2-related factor-2 (Nrf2) plays a crucial role in defending cells against oxidative stress by activating genes that produce antioxidants. L-sulforaphane (SFN), a drug that activates Nrf2, reduces damage caused by hyperglycemia. Hyperglycemic Wistar rats and HEK 293 cells maintained in hyperglycemic medium exhibited decreased Nrf2 nuclear translocation and reduced expression and activity of antioxidant enzymes. SFN treatment increased Nrf2 activity and reversed decreased renal function, oxidative stress and cell death associated with hyperglycemia. To investigate mechanisms involved in hyperglycemia-induced reduced Nrf2 activity, we addressed whether Nrf2 is modified by O-linked ß-N-acetylglucosamine (O-GlcNAc), a post-translational modification that is fueled in hyperglycemic conditions. In vivo, hyperglycemia increased O-GlcNAc-modified Nrf2 expression. Increased O-GlcNAc levels, induced by pharmacological inhibition of OGA, decreased Nrf2 activity in HEK 293 cells. In conclusion, hyperglycemia reduces Nrf2 activity, promoting oxidative stress, cell apoptosis and structural and functional renal damage. Pharmacological treatment with SFN attenuates renal injury. O-GlcNAcylation negatively modulates Nrf2 activity and represents a potential mechanism leading to oxidative stress and renal damage in hyperglycemic conditions.

Endothelial KIR2 channel dysfunction in aged cerebral parenchymal arterioles.

Aging is associated with cognitive decline via incompletely understood mechanisms. Cerebral microvascular dysfunction occurs in aging, particularly impaired endothelium-mediated dilation. Parenchymal arterioles are bottlenecks of the cerebral microcirculation, and dysfunction causes a mismatch in nutrient demand and delivery, leaving neurons at risk. Extracellular nucleotides elicit parenchymal arteriole dilation by activating endothelial purinergic receptors (P2Y), leading to opening of K+ channels, including inwardly-rectifying K+ channels (KIR2). These channels amplify hyperpolarizing signals, resulting in dilation. However, it remains unknown if endothelial P2Y and KIR2 signaling are altered in brain parenchymal arterioles during aging. We hypothesized that aging impairs endothelial P2Y and KIR2 function in parenchymal arterioles. We observed reduced dilation to the purinergic agonist 2-methyl-S-ADP (1 µM) in arterioles from Aged (>24-month-old) mice when compared to Young (4-6 months of age) despite similar hyperpolarization in endothelial cells tubes. No differences were observed in vasodilation or endothelial cell hyperpolarization to activation of small- and intermediate-conductance Ca2+-activated K+ channels (KCa2.3 / KCa3.1) by NS309. Hyperpolarization to 15 mM [K+]E was smaller in Aged than Young mice, despite a paradoxical increased dilation in Aged arterioles to 15 mM [K+]E that was unchanged by endothelium removal. KIR2 Inhibition attenuated vasodilatory responses to 15 mM [K+]E and 1 µM 2-me-S-ADP in both Young and Aged arterioles. Further, we observed a significant increase in myogenic tone in Aged parenchymal arterioles, which was not enhanced by endothelium removal. We conclude that aging impairs endothelial KIR2 channel function in the cerebral microcirculation with possible compensation by smooth muscle cells.

Testing the Induction of Metritis in Healthy Postpartum Primiparous Cows Challenged with a Cocktail of Bacteria.

Metritis is a postpartum uterine disease with greater incidence in primiparous than in multiparous cows. In primiparous cows, the impact on production and health is lessened, presumably due to a superior immune response. Here, we tested whether an in vivo model of clinical metritis induction developed for postpartum multiparous Holstein cows would produce similar results in primiparous cows. Thirty-six cows were randomly assigned to one of three groups and received intrauterine infusion within 24 h of parturition. The controls were infused with sterile saline; the low-dose group received a bacterial cocktail containing 103 cfu of Escherichia coli, Trueperella pyogenes, and Fusobacterium necrophorum; and the high-dose group were infused with 106 cfu of the same cocktail. Production, health traits, and the vaginal discharge culture were assessed daily, from enrollment until 14 d in milk. Clinical metritis occurred in 64% of high-dose cows, 33% of the controls, and 42% of low-dose cows, with no significant difference of incidence between groups. However, when accounting by time, high-dose cows had a 2.7 times greater hazard of metritis compared with the controls. The bacterial challenge affected milk production and dry matter intake tended to decrease. In the high-dose group, a greater growth of F. necrophorum in the selective medium was also observed, suggesting an association with metritis. Therefore, this study suggests intrauterine inoculation with 106 cfu of this bacterial cocktail elicits physical and clinical outcomes consistent with clinical metritis.

BK Ca nitrosylation is associated with cerebral microvascular dysfunction in female 5x-FAD mice.

Cerebral microvascular dysfunction and nitro-oxidative stress are present in patients with Alzheimer's disease (AD) and may contribute to disease progression and severity. Large conductance Ca 2+ -activated K + channels (BK Ca ) play an essential role in vasodilatory responses and maintenance of myogenic tone in resistance arteries. BK Ca can be modified in a pro-nitro-oxidative environment, resulting in decreased activity and vascular hyper-contractility, which can compromise cerebral blood flow regulation. We hypothesized that reductions in BK Ca function in cerebral arteries, as a consequence of nitro-oxidative stress, are associated with blunted neurovascular responses in the 5x-FAD model of AD. Using pressure myography, we observed that posterior communicating arteries (PComA) from 5 months-old female 5x-FAD mice showed higher spontaneous myogenic tone than wild-type (WT) littermates. Constriction to the BK Ca blocker iberiotoxin (30 nM) was smaller in 5x-FAD than WT, suggesting lower basal BK Ca activity, which was independent of alterations in intracellular Ca 2+ transients or BK Ca mRNA expression. These vascular changes were associated with higher levels of oxidative stress in female 5x-FAD and a higher level of S-nitrosylation in the BK Ca α-subunit. In females, pre-incubation of PComA from 5x-FAD with the reducing agent DTT (10 µM) rescued iberiotoxin-induced contraction. Female 5x-FAD mice showed increased expression of iNOS mRNA, lower resting cortical perfusion atop the frontal cortex, and impaired neurovascular coupling responses. No significant differences between male 5x-FAD and WT were observed for all parameters above. These data suggest that the exacerbation in BK Ca S-nitrosylation contributes to cerebrovascular and neurovascular impairments in female 5x-FAD mice. Significance Statement: Cerebral vascular dysfunction is increasingly recognized as a hallmark of Alzheimer's disease and other dementias. Impaired microvascular regulation can lead to deficits in blood flow to the brain. An intrinsic property of the resistance vasculature is to constrict when pressurized (myogenic tone), generating a vasodilatory reserve. Detrimental over-constriction is prevented by vascular feedback mechanisms, including the opening of large-conductance Ca 2+ -activated K + channels (BK Ca ). Here, using a combination of molecular biology tools with ex vivo and in vivo vascular assessments, we show a novel mechanism associated with BK Ca dysfunction in the cerebral microvasculature of female 5x-FAD mice. We report increased BK Ca S-nitrosylation linked to reduced activity and, consequently, higher basal myogenic tone. These changes were associated with lower perfusion of the frontal cortex and impaired neurovascular reactivity, suggesting that nitro-oxidative stress is an important mechanism of vascular dysfunction in Alzheimer's disease.

Hypothalamic Kisspeptin Neurons as a Target for Whole-Cell Patch-Clamp Recordings.

Kisspeptins are essential for the maturation of the hypothalamic-pituitary-gonadal (HPG) axis and fertility. Hypothalamic kisspeptin neurons located in the anteroventral periventricular nucleus and rostral periventricular nucleus, as well as the arcuate nucleus of the hypothalamus, project to gonadotrophin-releasing hormone (GnRH) neurons, among other cells. Previous studies have demonstrated that kisspeptin signaling occurs through the Kiss1 receptor (Kiss1r), ultimately exciting GnRH neuron activity. In humans and experimental animal models, kisspeptins are sufficient for inducing GnRH secretion and, consequently, luteinizing hormone (LH) and follicle stimulant hormone (FSH) release. Since kisspeptins play an essential role in reproductive functions, researchers are working to assess how the intrinsic activity of hypothalamic kisspeptin neurons contributes to reproduction-related actions and identify the primary neurotransmitters/neuromodulators capable of changing these properties. The whole-cell patch-clamp technique has become a valuable tool for investigating kisspeptin neuron activity in rodent cells. This experimental technique allows researchers to record and measure spontaneous excitatory and inhibitory ionic currents, resting membrane potential, action potential firing, and other electrophysiological properties of cell membranes. In the present study, crucial aspects of the whole-cell patch-clamp technique, known as electrophysiological measurements that define hypothalamic kisspeptin neurons, and a discussion of relevant issues about the technique, are reviewed.

Toxicological Effects of Copaiba Oil (Copaifera spp.) and Its Active Components.

Vegetable oils are among the most important traditional resources of Amazonia. Oleoresins are a type of oil that have interesting characteristics and highly bioactive properties with pharmacological potential. Oleoresins produced in the trunks of Copaifera (Fabaceae) spp. trees, known as copaiba oils, are made up of terpenes from the sesquiterpene (volatile) and diterpene (resinous) classes, but in amounts that vary between species and depending on several factors, such as soil type. Despite being used for medicinal purposes, via topical and oral application, the toxic effects of copaiba oils and their constituents are little known. The current paper reviews the toxicological studies, both in vitro and in vivo, described in the literature for copaiba oils, as well as the cytotoxic characteristics (against microorganisms and tumor cells) in in silico, in vitro and in vivo models for the sesquiterpenes and diterpenes that make up these oils.

Genotoxicity and cytotoxicity of textile production effluents, before and after Bacillus subitilis bioremediation, in Astyanax lacustris (Pisces, Characidae).

Textile effluents may be highly toxic and mutagenic. Monitoring studies are important for sustaining the aquatic ecosystems contaminated by these materials, which can cause damage to organisms and loss of biodiversity. We have evaluated the cyto- and genotoxicity of textile effluents on erythrocytes of Astyanax lacustris, before and after bioremediation by Bacillus subitilis treatment. We tested 60 fish (five treatment conditions, four fish per condition, in triplicate). Fish were exposed to contaminants for 7 days. The assays used were biomarker analysis, the micronucleus (MN) test, analysis of cellular morphological changes (CMC), and the comet assay. All concentrations of effluent tested, and the bioremediated effluent, showed damage significantly different from the controls. We conclude that water pollution assessment can be accomplished with these biomarkers. Biodegradation of the textile effluent was only partial, indicating the need for more thorough bioremediation to effect complete neutralization of toxicity.

Cerebral arteriolar and neurovascular dysfunction after chemically induced menopause in mice.

Cognitive decline is linked to decreased cerebral blood flow, particularly in women after menopause. Impaired cerebrovascular function precedes the onset of dementia, possibly because of reduced functional dilation in parenchymal arterioles. These vessels are bottlenecks of the cerebral microcirculation, and dysfunction can limit functional hyperemia in the brain. Large-conductance Ca2+-activated K+ channels (BKCa) are the final effectors of several pathways responsible for functional hyperemia, and their expression is modulated by estrogen. However, it remains unknown whether BKCa function is altered in cerebral parenchymal arterioles after menopause. Using a chemically induced model of menopause, the 4-vinylcyclohexene diepoxide (VCD) model, which depletes follicles while maintaining intact ovaries, we hypothesized that menopause would be associated with reduced functional vasodilatory responses in cerebral parenchymal arterioles of wild-type mice via reduced BKCa function. Using pressure myography of isolated parenchymal arterioles, we observed that menopause (Meno) induced a significant increase in spontaneous myogenic tone. Endothelial function, assessed as nitric oxide production and dilation after cholinergic stimulation or endothelium-dependent hyperpolarization pathways, was unaffected by Meno. BKCa function was significantly impaired in Meno compared with control, without changes in voltage-gated K+ channel activity. Cerebral functional hyperemia, measured by laser-speckle contrast imaging during whisker stimulation, was significantly blunted in Meno mice, without detectable changes in basal perfusion. However, behavioral testing identified no change in cognition. These findings suggest that menopause induces cerebral microvascular and neurovascular deficits.NEW & NOTEWORTHY Cerebral parenchymal arterioles from menopause mice showed increased myogenic tone. We identified an impairment in smooth muscle cell BKCa channel activity, without a reduction in endothelium-dependent dilation or nitric oxide production. Microvascular dysfunction was associated with a reduction in neurovascular responses after somatosensory stimulation. Despite the neurovascular impairment, cognitive abilities were maintained in menopausal mice.

Gap junctions regulate the activity of AgRP neurons and diet-induced obesity in male mice.

Recent studies indicated an important role of connexins, gap junction proteins, in the regulation of metabolism. However, most of these studies focused on the glial expression of connexins, whereas the actions of connexins in neurons are still poorly investigated. Thus, the present study had the objective to investigate the possible involvement of gap junctions, and in particular connexin 43 (CX43), for the central regulation of energy homeostasis. Initially, we demonstrated that hypothalamic CX43 expression was suppressed in fasted mice. Using whole-cell patch-clamp recordings, we showed that pharmacological blockade of gap junctions induced hyperpolarization and decreased the frequency of action potentials in 50-70% of agouti-related protein (AgRP)-expressing neurons, depending on the blocker used (carbenoxolone disodium, TAT-Gap19 or Gap 26). When recordings were performed with a biocytin-filled pipette, this intercellular tracer was detected in surrounding cells. Then, an AgRP-specific CX43 knockout (AgRPΔCX43) mouse was generated. AgRPΔCX43 mice exhibited no differences in body weight, adiposity, food intake, energy expenditure and glucose homeostasis. Metabolic responses to 24 h fasting or during refeeding were also not altered in AgRPΔCX43 mice. However, AgRPΔCX43 male, but not female mice, exhibited a partial protection against high-fat diet-induced obesity, even though no significant changes in energy intake or expenditure were detected. In summary, our findings indicate that gap junctions regulate the activity of AgRP neurons, and AgRP-specific CX43 ablation is sufficient to mildly prevent diet-induced obesity specifically in males.

Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction.

BACKGROUND AND PURPOSE: Metabolic and vascular dysfunction are common features of obesity. Aryl hydrocarbon receptor (AhR) regulates lipid metabolism and vascular homeostasis, but whether vascular AhR are activated in obesity or have a protective and/or harmful effects on vascular function in obesity are unknown. Our study addresses whether AhR activation contributes to obesity-associated vascular dysfunction and the mechanisms involved in these AhR effects. EXPERIMENTAL APPROACH: Male AhR KO (Ahr-/- ) and WT mice were fed either control or a HF (high-fat) diet for 10 weeks. Metabolic and inflammatory parameters were measured in serum and adipose tissue. Vascular reactivity (isometric force) was evaluated using a myography. Endothelial NOS (eNOS) and AhR protein expression was determined by western blot, Cyp1A1 and Nos3 gene expression by RT-PCR and.NO production was quantified by DAF fluorescence. KEY RESULTS: HF diet increased total serum HDL and LDL, as well as vascular AhR protein expression and proinflammatory cytokines in the adipose tissue. HF diet decreased endothelium-dependent vasodilation. AhR deletion protected mice from HF diet-induced dyslipidaemia, weight gain and inflammatory processes. HF diet-induced endothelial dysfunction was attenuated in Ahr-/- mice. Vessels from Ahr-/- mice exhibited a greater NO reserve. In cultured endothelial cells, lysophosphatidylcholine (LPC) a major component of LDL and oxidized LDL [oxLDL]) reduced Nos3 gene expression and NO production. Antagonism of the AhR inhibited LPC effects on endothelial cells and induced decreased endothelium-dependent vasodilation. CONCLUSION AND IMPLICATIONS: AhR deletion attenuates HF diet-induced dyslipidaemia and vascular dysfunction by improving eNOS/NO signalling. Targeting AhRs may prevent obesity-associated vascular dysfunction.

Blockade of protease-activated receptor 2 attenuates allergenmediated acute lung inflammation and leukocyte recruitment in mice.

Protease-activated receptor (PAR)2 has been implicated in mediating allergic airway inflammation.We investigate the role of PAR2 in lung inflammation and neutrophil and eosinophil recruitment into the lungs in amousemodel of shortterm acute allergic inflammation. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with the PAR2 antagonist ENMD1068 or with the PAR2-activating peptide (PAR2-AP) 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs, trachea and lymph nodes were removed after the last challenge to analyze the airway inflammation. PAR2 blockade reduced OVA-induced eosinophil and neutrophil counts, CXCL1, CCL5, amphiregulin, and interleukin (IL)-6 and 13 levels.Moreover, PAR2 blockade reduced OVA-induced PAR2 expression in cells present in BALF 2 hour after OVA challenge, and PAR2-AP acted synergistically with OVA promoting eosinophil recruitment intoBALF and increased IL-4 and IL-13 levels in lymph nodes. Conversely, PAR2 blockade increased IL- 10 levels when compared with OVA-treated mice. Our results provide evidence for a mechanism by which PAR2 meditates acute lung inflammation triggered by multiple exposures to allergen through a modulatory role on cytokine production and vascular permeability implicated in the lung diseases such as asthma.

In vivo anti-inflammatory and antinociceptive effects, and in vitro antioxidant, antiglycant and anti-neuroinflammatory actions of Syzygium malaccense.

Syzygium malaccense is popularly used to treat inflammation and pain-related ailments. The species was assessed regarding its antioxidant, antiglycant, anti-inflammatory, including anti-neuroinflammatory, and antinociceptive activities. Different models were employed to measure S. malaccense extract (ESM) antioxidant activity. The antiglycant activity was determined using the glucose-induced protein glycation model. LPS-induced neuroinflammation on murine BV-2 microglial cell line was used for anti-neuroinflammatory activity evaluation. The croton oil-induced ear edema test was accomplished to evaluate the in vivo anti-inflammatory activity. Acetic acid-induced writhing together with formalin-induced paw licking assays were performed to evaluate the antinociceptive potential. Finally, the chemical characterization was accomplished by a UHPLC-MS analysis. ESM presented relevant antioxidant and antiglycant activity. NO production by BV-2 cells was reduced, indicating the relevant neuroprotective activity. ESM significantly decreased the mice ear edema induced by croton oil and the nociceptive stimulus induced by acetic acid and formalin by central and peripheral mechanisms. The flavonoids myricitrin, myricetin and quercetin were identified and, as far as we know, the alkaloid reserpine was reported in the species for the first time. The antioxidant and antiglycant potential of ESM, may be related to the in vivo anti-inflammatory and antinociceptive effects, and to the in vitro neuroinflammation inhibition.

Estratégias de prevenção de lesões por pressão facial ocasionadas pelo uso da posição prona / Strategies for the prevention of facial pressure injuries caused by the use of the prone position / Estrategias de prevención de lesiones por presión facial ocasionadas por el uso de la posición prona

Objetivo:Identificar as principais estratégias para prevenção de lesões por pressão faciais ocasionadas pelo uso de posição prona. Métodos:Revisão integrativa de literatura, realizada durante o mês de março de 2021. Foram pesquisados artigos nas bases de dados da MEDLINE, LILACS, BDENF e IBECS. Os artigos selecionados foram redigidos nos idiomas inglês, português e espanhol, entre 2016 e 2021. Foram excluídos os duplicados e os que não incluíam a temática abordada. Inicialmente, foram identificados 29 artigos. Após a aplicação dos critérios de inclusão e exclusão, resultaram 10 artigos para análise. Resultados: Das complicações relacionadas ao uso de posição prona, 10 (100%) dos estudos abordam a lesão por pressão como a principal complicação dessa manobra terapêutica. Quanto às estratégias de prevenção, os estudos analisados citam a mudança de decúbito associada ao uso de coxim e hidrocolóides como principais métodos preventivos. Conclusão: Foram identificadas as seguintes estratégias de prevenção de lesão por pressão facial pelo uso de posição prona: mudança de decúbito em tempos pré-estabelecidos; uso de dispositivos que proporcionam alívio de pontos de pressão, tais como os coxins e hidrocolóides; e a utilização de materiais de baixo custo e fácil acesso, como esponjas cirúrgicas adaptadas, respeitando as estruturas anatômicas de cada paciente.

Objective:Identify the main strategies for preventing facial pressure injuries caused by the use of the prone position. Methods: Integrative literature review, carried out during the month of March 2021. Articles were searched in the MEDLINE, LILACS, BDENF and IBECS databases. The selected articles were written in English, Portuguese and Spanish, between 2016 and 2021. Duplicates and those that did not include the topic addressed were excluded. Initially, 29 articles were identified. After applying the inclusion and exclusion criteria, 10 articles resulted for analysis. Results: Of the complications related to the use of the prone position, 10 (100%) of the studies address the pressure injury as the main complication of this therapeutic maneuver. As for prevention strategies, the studies analyzed cite the change in position associated with the use of pads and hydrocolloids as the main preventive methods. Conclusion: The following strategies to prevent facial pressure injury by using the prone position were identified: change of decubitus at pre-established times; use of devices that provide relief from pressure points, such as pads and hydrocolloids; and the use of low-cost and easily accessible materials, such as adapted surgical sponges, respecting the anatomical structures of each patient.

Objetivo:Identificar las principales estrategias para la prevención de lesiones por presión faciales ocasionadas por el uso de posición prona. Métodos: Revisión integrativa de literatura, realizada durante el mes de marzo del 2021. Fueron investigados artículos en las bases de datos de MEDLINE, LILACS, BDENF e IBECS. Los artículos seleccionados fueron redactados en los idiomas inglés, portugués y español, entre el 2016 y el 2021. Fueron excluidos los duplicados y los que no incluían la temática abordada. Inicialmente, fueron identificados 29 artículos. Después de la aplicación de los criterios de inclusión y exclusión, resultaron 10 artículos para análisis. Resultados: De las complicaciones relacionadas al uso de la posición prona, 10 (100%) de los estudios abordan la lesión por presión como la principal complicación de esta maniobra terapéutica. Con respecto a las estrategias de prevención, los estudios analizados citan el cambio de decúbito asociada al uso de apoyo e hidrocoloides como principales métodos preventivos. Conclusión: Fueron identificadas las siguientes estrategias de prevención de lesión por presión facial por el uso de posición prona: cambio de decúbito en tiempos preestablecidos; uso de dispositivos que proporcionan alivio de puntos de presión, tales como los apoyos e hidrocoloides; y la utilización de materiales de bajo costo y fácil acceso, como esponjas quirúrgicas adaptadas, respetando las estructuras anatómicas de cada paciente.

Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone.

High levels of aldosterone (Aldo) trigger oxidative stress and vascular dysfunction independent of effects on blood pressure. We sought to determine whether Aldo disrupts Nrf2 signaling, the main transcriptional factor involved in antioxidant responses that aggravate cell injury. Thoracic aorta from male C57Bl/6J mice and cultured human endothelial cells (EA.hy926) were stimulated with Aldo (100 nM) in the presence of tiron [reactive oxygen species (ROS) scavenger, eplerenone [mineralocorticoid receptor (MR) antagonist], and L-sulforaphane (SFN; Nrf2 activator). Thoracic aortas were also isolated from mice infused with Aldo (600 µg/kg per day) for 14 days. Aldo decreased endothelium-dependent vasorelaxation and increased ROS generation, effects prevented by tiron and MR blockade. Pharmacological activation of Nrf2 with SFN abrogated Aldo-induced vascular dysfunction and ROS generation. In EA.hy926 cells, Aldo increased ROS generation, which was prevented by eplerenone, tiron, and SFN. At short times, Aldo-induced ROS generation was linked to increased Nrf2 activation. However, after three hours, Aldo decreased the nuclear accumulation of Nrf2. Increased Keap1 protein expression, but not activation of p38 MAPK, was linked to Aldo-induced reduced Nrf2 activity. Arteries from Aldo-infused mice also exhibited decreased nuclear Nrf2 and increased Keap1 expression. Our findings suggest that Aldo reduces vascular Nrf2 transcriptional activity by Keap1-dependent mechanisms, contributing to mineralocorticoid-induced vascular dysfunction.