Superoxide radical anion (O2⋅‒) and other reactive oxygen species are constantly produced during respiration. In mitochondria, the dismutation of O2⋅‒ is accelerated by the mitochondrial superoxide ...dismutase 2 (SOD2), an enzyme that has been traditionally associated with antioxidant protection. However, increases in SOD2 expression promote oxidative stress, indicating that there may be a prooxidant role for SOD2. Here we show that SOD2, which normally binds manganese, can incorporate iron and generate an alternative isoform with peroxidase activity. The switch from manganese to iron allows FeSOD2 to utilize H2O2 to promote oxidative stress. We found that FeSOD2 is formed in cultured cells and in vivo. FeSOD2 causes mitochondrial dysfunction and higher levels of oxidative stress in cultured cells and in vivo. We show that formation of FeSOD2 converts an antioxidant defense into a prooxidant peroxidase that leads to cellular changes seen in multiple human diseases.
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•Mitochondrial SOD2 incorporated with iron (FeSOD2) is a prooxidant peroxidase•Cells and animals accumulate FeSOD2 when manganese-to-iron levels are low•FeSOD2 in cells and animals leads to oxidative stress and mitochondrial dysfunction
Ganini et al. demonstrate that incorporation of iron over manganese by the mitochondrial superoxide dismutase (SOD2) generates a prooxidant peroxidase in mitochondria of human cells and mice. They show that FeSOD2 formation leads to mitochondrial dysfunction and oxidative stress.
DC. is a plant species from the Asteraceae family that is endemic to Brazil. Despite the great importance of
genus, no study has been carried out regarding either the phytochemical composition of
or ...the evaluation of its larvicidal potential. Considering the intrinsic immiscibility of essential oils, this study shows larvicidal nanoemulsions containing the
phytochemically characterized essential oil and its main constituent against
. The major compound found was d-limonene (25.7%). The essential oil inhibited the acetylcholinesterase, one of the main targets of insecticides. The required hydrophile-lipophile balance of both nanoemulsions was 15.0. The mean droplet sizes were around 90.0 nm, and no major alterations were observed after 24 h of preparation for both formulations. After 48 h of treatment, the estimated LC
values were 118.94 μg mL
and 81.19 μg mL
for
essential oil and d-limonene nanoemulsions, respectively. Morphological alterations evidenced by scanning electron micrography were observed on the larvae treated with the d-limonene nanoemulsion. This paper demonstrated a simple and ecofriendly method for obtaining
essential oil and d-limonene aqueous nanoemulsions by a non-heating and solvent-free method, as promising alternatives for
control.
Tidal volume (V
) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ...ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high V
should not be injurious. The present study aimed to investigate the impact of different V
levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation interleukin (IL)-6, alveolar stretch (amphiregulin), epithelial club cell secretory protein (CC)16 and endothelial intercellular adhesion molecule (ICAM)-1 cell injury, and extracellular matrix damage syndecan-1, decorin, and metalloproteinase (MMP)-9 in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received
lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different V
levels (
= 7/group): (1) V
= 6 mL/kg and RR adjusted to normocapnia; (2) V
= 13 mL/kg; and 3) V
= 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as (ΔFormula: see text/Est,
)/2× RR (ΔP,
= transpulmonary driving pressure, Est,
= static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while V
gradually increased. ΔP,
and mechanical energy were higher in V
= 22 mL/kg than V
= 6 mL/kg and V
= 13 mL/kg (
< 0.001 for both). Accordingly, DAD score increased in V
= 22 mL/kg compared to V
= 6 mL/kg and V
= 13 mL/kg 23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18),
< 0.05, respectively. V
= 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than V
= 6 mL/kg. Multiple linear regression analyses indicated that V
was able to predict changes in IL-6 and CC16, whereas ΔP,
predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high V
resulted in VILI. V
control seems to be more important than RR control to mitigate VILI.
Intra-abdominal hypertension (IAH) may co-occur with the acute respiratory distress syndrome (ARDS), with significant impact on morbidity and mortality. Lung-protective controlled mechanical ...ventilation with low tidal volume and positive end-expiratory pressure (PEEP) has been recommended in ARDS. However, mechanical ventilation with spontaneous breathing activity may be beneficial to lung function and reduce lung damage in mild ARDS. We hypothesized that preserving spontaneous breathing activity during pressure support ventilation (PSV) would improve respiratory function and minimize ventilator-induced lung injury (VILI) compared to pressure-controlled ventilation (PCV) in mild extrapulmonary acute lung injury (ALI) with IAH. Thirty Wistar rats (334±55g) received Escherichia coli lipopolysaccharide intraperitoneally (1000μg) to induce mild extrapulmonary ALI. After 24h, animals were anesthetized and randomized to receive PCV or PSV. They were then further randomized into subgroups without or with IAH (15 mmHg) and ventilated with PCV or PSV (PEEP = 5cmH2O, driving pressure adjusted to achieve tidal volume = 6mL/kg) for 1h. Six of the 30 rats were used for molecular biology analysis and were not mechanically ventilated. The main outcome was the effect of PCV versus PSV on mRNA expression of interleukin (IL)-6 in lung tissue. Regardless of whether IAH was present, PSV resulted in lower mean airway pressure (with no differences in peak airway or peak and mean transpulmonary pressures) and less mRNA expression of biomarkers associated with lung inflammation (IL-6) and fibrogenesis (type III procollagen) than PCV. In the presence of IAH, PSV improved oxygenation; decreased alveolar collapse, interstitial edema, and diffuse alveolar damage; and increased expression of surfactant protein B as compared to PCV. In this experimental model of mild extrapulmonary ALI associated with IAH, PSV compared to PCV improved lung function and morphology and reduced type 2 epithelial cell damage.
Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we ...demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.
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► Determination of 27 elements in the steps of the synthesis of FAMEs from microalga. ► Multielement determination by ICP-MS and ICP OES after microwave-assisted digestion. ► Residual ...biomass could be used for animal feed production.
This work reports, for the first time, the determination of major and trace elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, La, Mg, Mn, Mo, Na, Ni, P, Pb, S, Se, Sn, Sr, Ti, Tl, U, V, and Zn) in the fractions of the synthesis of fatty acid methyl esters (FAMEs). These include fresh microalgae, residual biomass, lipid fraction, crude FAMEs, insoluble fraction and purified FAMEs from microalgae Chlorella sp. A microwave-assisted digestion procedure in closed vessels was applied for sample digestion and subsequent element determination by inductively coupled plasma-based techniques. The proposed method was suitable for the multielement determination in FAMEs and its fractions obtained from microalgae. The element concentration was compared with results found in the literature and a careful discussion about the use of residual biomass for different applications was performed.
•PVA films functionalized with nitric oxide releasing SNO groups were prepared.•PVA-SNO films were combined with a layer of micellar Pluronic F127 hydrogel.•Combined PVA-SNO films/F127 hydrogel ...reduced the rate of NO delivery to tissues.•Topical application of PVA-SNO films/F127 hydrogel improved wound healing.•A new approach for NO-releasing active wound dressings is proposed.
Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing.
Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to ...first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 µg mL
. In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast-hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.
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Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) (F127) hydrogels have been used to deliver nitric oxide (NO) topically in biomedical applications. Here, ...the effect of F127 microenvironments on the photochemical NO release from S-nitrosoglutathione (GSNO) was investigated in F127 solutions 7.6 wt% 15 wt% and 22.5 wt% at 15 °C and 37 °C. Small-angle X-ray Scattering (SAXS) and Differential Scanning Calorimetry (DSC) measurements, along with proton Nuclear Magnetic Resonance (1H NMR) spectral shifts and T2 relaxation data at six different concentration-temperature conditions, allowed identifying F127 microphases characterized by: a sol phase of unimers; micelles in non-defined periodic order, and a gel phase of cubic packed micelles. Kinetic measurements showed that GSNO photodecompositon proceeds faster in micellized F127 where GSNO is segregated to the intermicellar microenvironment. Real time kinetic monitoring of NO release and T2 relaxation profiles showed that NO is preferentially partitioned into the hydrophobic PPO cores of the F127 micelles, with the consequent decrease in its rate of release to the gas phase. These results show that F127 microphases affect both the kinetics of GSNO photodecomposition and the rate of NO escape and can be used to modulate the photochemical NO delivery from F127/GSNO solutions.
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